More than 50 experts on the use of deep brainstimulation for treatment of tremors and other symptoms of Parkinson’s disease have reached general agreement on when the surgical procedure should be considered and which patients might reap most benefits, a new report says.
The report, published in the online edition of Archives of Neurology, says the best candidates for deep brain stimulation are those who can’t tolerate the side effects ofmedication and those who don’t suffer from significant active cognitive or psychiatric problems but who do suffer from tremors or motor skills control.
In a deep brain stimulation procedure, a neurosurgeon surgically implants a neurostimulator in the brain in the location where abnormal electrical nerve signals generate the tremors and other symptoms common in Parkinson’s patients. The neurostimulator generates electric stimulation to the area to block the signals.
The report also says that:
Deep brain stimulation surgery is best performed by an experienced team and neurosurgeon who have expertise in stereotactic neurosurgery — microsurgery deep within the brain that is based on a three-dimensional coordinate system using advanced neuroimaging.
Deep brain stimulation is effective when used in the two most commonly treated areas of the brain, called the subthalamic nuclei and the globus pallidus pars interna. But treatment in the subthalamic nuclei may cause increased depressionand other symptoms in some patients.
Surgical removal of the area of the brain that causes Parkinson’s disease is an effective alternative and should be considered as an alternative in some people.
Surgical complication rates vary, with infection being the mostly commonly reported side effect of deep brain stimulation.
Making an Informed Decision
“We know that very little accessible information is out there to help a Parkinson’s patient make an informed decision as to whether he or she would be a good candidate for deep brain stimulation,” says report lead author Jeff Bronstein, MD, PhD, a professor of neurology at University of California, Los Angeles, in a news release.
Surgical studies take a long time, and what’s known about deep brain stimulation is focused, limited, and often written by one group, reflecting their opinions and biases, he says.
Bronstein says the results of a meeting in April 2009 of the Parkinson’s experts are intended to clarify some issues about the use of deep brain stimulation.
The FDA approved deep brain stimulation as a treatment for Parkinson’s disease in 2002, and since then more than 70,000 people have undergone the procedure. The authors write than more than 30% of failures of deep brain stimulation have been due to “inappropriate indications for surgery.”
The report says long-term improvements have been shown for up to five years for a number of Parkinson’s disease symptoms.
The experts caution that Parkinson’s disease continues to progress after deep brain stimulation.
Tuesday, October 19, 2010
Sunday, October 10, 2010
Depression Treatment | Depression – Symptoms, Causes And Treatment Options
Depression is a complex of psychological and physical symptoms. Low mood level or sadness is often the most prominent symptom. The common property of these symptoms is a decreased activity level in parts of the brain.
THE SYMPTOMS OF DEPRESSION
Depression may give one or more of these symptoms:
-Low mood level or sadness.
-Lack of joy or interest in activities that were joyful before.
-Pessimism.
-Feel of guilt of something without any substantial reason to feel so.
-Inferiority thoughts.
-Irritability.
-Slowness in the thought process.
-Slowness in interpreting sensorial stimuli.
-Slowness of digestion or other internal physical processes, and symptoms caused by this slowness, for example inflated stomach, constipation or difficulties by urination.
-Slow physical reactions.
Depression can be a mild disease that only causes some annoyance in the daily life, but can also get very serious and make a person totally unable to work and unable to participate in social life. By depression of some severity, there is also a greater risk of suicide.
Depression can occur in all age classes. In teenagers lack of interest in school work, withdrawal from social life and difficult mood can be signs of depression.
THE PHYSIOLOGICAL CHANGES THAT PRODUCE THE SYMPTOMS
By depression there is a decreased amount of neurotransmitters in parts of the central nervous system, mainly deficiency of serotonin, but also to some extend of noradrenalin, acetylcholine, dopamine or gamma-amino-butyric acid (GABA), or the nerve cells do not react properly by stimulation from neurotransmitters. A neurotransmitter is a signal substance that transmits the nerve signal through the junctions between two nerve cells.
Serotonin and noradrenalin cause nerve cells to send impulses along to other nerve cells, and thus increase the activity in the brain. Deficiency of these substances causes slowness in parts of the brain, and that again causes the depressive symptoms.
The role of GABA is the opposite, namely to slow down some nerve impulses, mainly those causing anxiety and panic response. Lack of GABA causes higher anxiety and easier panic response. Yet, lack of this transmitter also seems to cause depressive symptoms. This is because a too high activity in some brain processes may slow down other processes.
There are many causes and subtypes of depression with different physiological mechanisms involved.
TYPES OF DEPRESSION
Depression is often divided into subtypes according to exhibited symptoms.
1. Mono-polar depression and dysthymic disorder
By mono-polar depression there are pure depressive symptoms. Mild cases of mono-polar disorder that do not affect a persons ability to work and to participate in social activities are often called dysthymic disorder.
2. Bipolar disorder (manic-depressive disease) and cyclothymic disorder
In this condition there are periods with symptoms of depression – the depressive phase, alternating with periods of elevated mood level with increased mental and physical activity – the manic phase. In the manic phase, the affected person also sleeps poorly and has concentration difficulties. A mild form of this disease is called cyclothymic disorder.
3. Manic disorder
This condition is characterized by abnormally elevated mood, by unrealistic optimism, by lack of sleep and by hyperactive behaviour. Many psychiatrists think that this disorder is simply the same disease as bipolar disorder where the depressive face has not yet occurred.
4. Depression with mainly physical symptoms
Sometimes the physical symptoms of depression are alone or dominant, as for example: Digestive problems, constipation, difficulties with urination, slow response to sensorial stimuli or slow physical reactions.
CAUSES OF DEPRESSION
Two or more factors can have an effect simultaneously to cause depression. Depression can be an independent disease, or a part of other disease. Depression is also divided into different subtypes according to cause.
1. Reactive depression
This disease is simply a result from psychological stress, physical struggle or mental straining without proper rest or sleep over a long time period. The straining will simply wear out the nervous system or deplete the organism from nutrient necessary for the nervous system to work properly.
2. Endogenous depression
When there has not been any period of stress, straining or lack of rest that can explain the condition, the condition is often called endogenous depression. Inheritance is thought to be a part of the cause.
3. Depression by physical disease
Depression or depressive symptoms may be a symptom of physical disease. This is perhaps the most common cause of depression. Generally there are three categories of diseases that give depression:
Diseases often associated with depression are: Heart disease, Parkinson’s disease, stroke, hypertension or Cushing’s syndrome.
Mononucleosis or flu may trigger depression that continues after the infection has gone.
By lack of thyroid hormones, hypothyroidism, the metabolism in the whole body is slowed down, including the production of neurotransmitters in the brain. Therefore depression is an important symptom of hypothyroidism.
4. Depressive symptoms as a consequence of unsound lifestyle
A general unsound lifestyle with too less exercise, too much of stimulants like alcohol, coffee or tea, too less of important nutrient and too much of sugar and fat may give depressive symptoms, as well as physical problems.
5. Postnatal depression
Women will often have a period of depression after pregnancy and berth of the baby Pregnancy and berth is physically and mentally exhausting, and may drain the body for nutrient. This in turn can cause depressive symptoms
.
6. Seasonal affective disorder
Depression can occur in cold and dark periods of the year and go away in warm and light periods. Light stimulates brain activity, and lack of light is a causative factor.
TREATMENT OF DEPRESSION
Serious or prolonged depression is often treated with anti-depressive medication. Medicines used against depression generally increase the level of neurotransmitters like serotonin in the central nervous system, or they mimic the neurotransmitters.
The medications mostly used today increase the serotonin concentration by decreasing the removal of serotonin from the space around nerve cells. Examples of this medication type are: Fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), escitalopram (Lexapro, Celexa), sentraline (zoloft).
By bipolar disorder in the manic face, heavy tranquilizers (neuroleptica) are used to stop the manic symptoms. By bipolar disorder, lithium salts are sometimes used to stabilize the condition, and prevent new outbreak of depressive or manic faces.
Psychotherapy is sometimes used by depression, usually in combination with medication.
Sometimes serious depression is treated by applying electric shock through the head, electroconvulsive therapy. The shock induces epileptic eruption of nerve signals through the brain and this gives cramps throughout the body. The cramps are alleviated or stopped by applying anaesthesia before the electroshock. This form of treatment is controversial, since it can cause memory loss and is suspected of causing brain damage. The possibility of brain damage is however denied by most psychiatrists.
By seasonal depression, light therapy maybe useful.
Adjustment of lifestyle should always be considered by depression or depressive symptoms. Lifestyle measures can sometimes be enough to cure depressive symptoms before a serious depression develop. Lifestyle adjustments can be:
– To slow down a stressful life with too much work or activities.
– Enough rest and sleep.
– A good diet with enough of necessary nutrients.
– Some physical exercise.
– Meditation.
– Supplement of vitamins, minerals, antioxidants, lecithin, amino acids and essential fatty acids.
– Stimulants like coffee or tea may help against depressive feelings in moderate amount. However, if you are a heavy user of these stimulants, you should cut down on your consumption.
There exist nutritional products in the marked to help against depressive symptoms. These contain ingredients that the brain uses as building blocks for neurotransmitters, for example amino acids and lecithin. They also often contain vitamins and minerals that the brain uses as tools to produce neurotransmitters, especially vitamin B6.
Supplements may further contain herbal extracts that trigger higher brain activity much like anti-depressive medications, but may have fewer side effects.
By: Knut Holt
THE SYMPTOMS OF DEPRESSION
Depression may give one or more of these symptoms:
-Low mood level or sadness.
-Lack of joy or interest in activities that were joyful before.
-Pessimism.
-Feel of guilt of something without any substantial reason to feel so.
-Inferiority thoughts.
-Irritability.
-Slowness in the thought process.
-Slowness in interpreting sensorial stimuli.
-Slowness of digestion or other internal physical processes, and symptoms caused by this slowness, for example inflated stomach, constipation or difficulties by urination.
-Slow physical reactions.
Depression can be a mild disease that only causes some annoyance in the daily life, but can also get very serious and make a person totally unable to work and unable to participate in social life. By depression of some severity, there is also a greater risk of suicide.
Depression can occur in all age classes. In teenagers lack of interest in school work, withdrawal from social life and difficult mood can be signs of depression.
THE PHYSIOLOGICAL CHANGES THAT PRODUCE THE SYMPTOMS
By depression there is a decreased amount of neurotransmitters in parts of the central nervous system, mainly deficiency of serotonin, but also to some extend of noradrenalin, acetylcholine, dopamine or gamma-amino-butyric acid (GABA), or the nerve cells do not react properly by stimulation from neurotransmitters. A neurotransmitter is a signal substance that transmits the nerve signal through the junctions between two nerve cells.
Serotonin and noradrenalin cause nerve cells to send impulses along to other nerve cells, and thus increase the activity in the brain. Deficiency of these substances causes slowness in parts of the brain, and that again causes the depressive symptoms.
The role of GABA is the opposite, namely to slow down some nerve impulses, mainly those causing anxiety and panic response. Lack of GABA causes higher anxiety and easier panic response. Yet, lack of this transmitter also seems to cause depressive symptoms. This is because a too high activity in some brain processes may slow down other processes.
There are many causes and subtypes of depression with different physiological mechanisms involved.
TYPES OF DEPRESSION
Depression is often divided into subtypes according to exhibited symptoms.
1. Mono-polar depression and dysthymic disorder
By mono-polar depression there are pure depressive symptoms. Mild cases of mono-polar disorder that do not affect a persons ability to work and to participate in social activities are often called dysthymic disorder.
2. Bipolar disorder (manic-depressive disease) and cyclothymic disorder
In this condition there are periods with symptoms of depression – the depressive phase, alternating with periods of elevated mood level with increased mental and physical activity – the manic phase. In the manic phase, the affected person also sleeps poorly and has concentration difficulties. A mild form of this disease is called cyclothymic disorder.
3. Manic disorder
This condition is characterized by abnormally elevated mood, by unrealistic optimism, by lack of sleep and by hyperactive behaviour. Many psychiatrists think that this disorder is simply the same disease as bipolar disorder where the depressive face has not yet occurred.
4. Depression with mainly physical symptoms
Sometimes the physical symptoms of depression are alone or dominant, as for example: Digestive problems, constipation, difficulties with urination, slow response to sensorial stimuli or slow physical reactions.
CAUSES OF DEPRESSION
Two or more factors can have an effect simultaneously to cause depression. Depression can be an independent disease, or a part of other disease. Depression is also divided into different subtypes according to cause.
1. Reactive depression
This disease is simply a result from psychological stress, physical struggle or mental straining without proper rest or sleep over a long time period. The straining will simply wear out the nervous system or deplete the organism from nutrient necessary for the nervous system to work properly.
2. Endogenous depression
When there has not been any period of stress, straining or lack of rest that can explain the condition, the condition is often called endogenous depression. Inheritance is thought to be a part of the cause.
3. Depression by physical disease
Depression or depressive symptoms may be a symptom of physical disease. This is perhaps the most common cause of depression. Generally there are three categories of diseases that give depression:
Diseases often associated with depression are: Heart disease, Parkinson’s disease, stroke, hypertension or Cushing’s syndrome.
Mononucleosis or flu may trigger depression that continues after the infection has gone.
By lack of thyroid hormones, hypothyroidism, the metabolism in the whole body is slowed down, including the production of neurotransmitters in the brain. Therefore depression is an important symptom of hypothyroidism.
4. Depressive symptoms as a consequence of unsound lifestyle
A general unsound lifestyle with too less exercise, too much of stimulants like alcohol, coffee or tea, too less of important nutrient and too much of sugar and fat may give depressive symptoms, as well as physical problems.
5. Postnatal depression
Women will often have a period of depression after pregnancy and berth of the baby Pregnancy and berth is physically and mentally exhausting, and may drain the body for nutrient. This in turn can cause depressive symptoms
.
6. Seasonal affective disorder
Depression can occur in cold and dark periods of the year and go away in warm and light periods. Light stimulates brain activity, and lack of light is a causative factor.
TREATMENT OF DEPRESSION
Serious or prolonged depression is often treated with anti-depressive medication. Medicines used against depression generally increase the level of neurotransmitters like serotonin in the central nervous system, or they mimic the neurotransmitters.
The medications mostly used today increase the serotonin concentration by decreasing the removal of serotonin from the space around nerve cells. Examples of this medication type are: Fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), escitalopram (Lexapro, Celexa), sentraline (zoloft).
By bipolar disorder in the manic face, heavy tranquilizers (neuroleptica) are used to stop the manic symptoms. By bipolar disorder, lithium salts are sometimes used to stabilize the condition, and prevent new outbreak of depressive or manic faces.
Psychotherapy is sometimes used by depression, usually in combination with medication.
Sometimes serious depression is treated by applying electric shock through the head, electroconvulsive therapy. The shock induces epileptic eruption of nerve signals through the brain and this gives cramps throughout the body. The cramps are alleviated or stopped by applying anaesthesia before the electroshock. This form of treatment is controversial, since it can cause memory loss and is suspected of causing brain damage. The possibility of brain damage is however denied by most psychiatrists.
By seasonal depression, light therapy maybe useful.
Adjustment of lifestyle should always be considered by depression or depressive symptoms. Lifestyle measures can sometimes be enough to cure depressive symptoms before a serious depression develop. Lifestyle adjustments can be:
– To slow down a stressful life with too much work or activities.
– Enough rest and sleep.
– A good diet with enough of necessary nutrients.
– Some physical exercise.
– Meditation.
– Supplement of vitamins, minerals, antioxidants, lecithin, amino acids and essential fatty acids.
– Stimulants like coffee or tea may help against depressive feelings in moderate amount. However, if you are a heavy user of these stimulants, you should cut down on your consumption.
There exist nutritional products in the marked to help against depressive symptoms. These contain ingredients that the brain uses as building blocks for neurotransmitters, for example amino acids and lecithin. They also often contain vitamins and minerals that the brain uses as tools to produce neurotransmitters, especially vitamin B6.
Supplements may further contain herbal extracts that trigger higher brain activity much like anti-depressive medications, but may have fewer side effects.
By: Knut Holt
Sunday, September 12, 2010
Researchers Explore Molecular Basis of Parkinson's Disease Using Yeast
Dr Tiago Fleming Outeiro describes how his group is slowly uncovering the molecular basis of Parkinson's disease by studying the associated human protein in yeast cells.
Parkinson's disease is a neurodegenerative disorder without any known cure that affects around 6 million people worldwide. The symptoms, which include rigidity, difficulty in initiating movements and resting tremors, are all related to the specific death of dopamine-producing neurons in the brain. These neurons characteristically contain protein deposits, known as Lewy bodies. A small protein called alpha-synuclein is the main component of these deposits.
Dr Outeiro explains how baker's yeast, Saccharomyces cerevisiae, is helping researchers learn how alpha-synuclein might lead to Parkinson's disease. "Yeast is a very simple but powerful model in which to study how alpha-synuclein actually works as, remarkably, many of the biochemical pathways involved are similar between yeast and humans," he said. "There is still a lot we don't know about the function of this protein, but we do know that even small increases in the level of alpha-synuclein in cells lead to cell death."
Dr Outeiro and colleagues screened a library of 115,000 small compounds to try and identify those that are able to block the toxic effects of alpha-synuclein. Several of these molecules have proved effective in preventing Parkinson's disease in worms and blocking alpha-synuclein toxicity in rat neurons. If developed further, they could form the basis of future Parkinson's disease treatments.
New treatments for neurodegenerative diseases are urgently needed. "With the ageing of the human population the number of people affected by Parkinson's disease will continue to increase. This means the disease will become an even greater problem for modern societies due to the tremendous socio-economic costs associated," Dr Outeiro said. "It's therefore imperative that treatments for such neurodegenerative diseases are developed. Our studies in yeast have enabled us make a step towards this."
Parkinson's disease is a neurodegenerative disorder without any known cure that affects around 6 million people worldwide. The symptoms, which include rigidity, difficulty in initiating movements and resting tremors, are all related to the specific death of dopamine-producing neurons in the brain. These neurons characteristically contain protein deposits, known as Lewy bodies. A small protein called alpha-synuclein is the main component of these deposits.
Dr Outeiro explains how baker's yeast, Saccharomyces cerevisiae, is helping researchers learn how alpha-synuclein might lead to Parkinson's disease. "Yeast is a very simple but powerful model in which to study how alpha-synuclein actually works as, remarkably, many of the biochemical pathways involved are similar between yeast and humans," he said. "There is still a lot we don't know about the function of this protein, but we do know that even small increases in the level of alpha-synuclein in cells lead to cell death."
Dr Outeiro and colleagues screened a library of 115,000 small compounds to try and identify those that are able to block the toxic effects of alpha-synuclein. Several of these molecules have proved effective in preventing Parkinson's disease in worms and blocking alpha-synuclein toxicity in rat neurons. If developed further, they could form the basis of future Parkinson's disease treatments.
New treatments for neurodegenerative diseases are urgently needed. "With the ageing of the human population the number of people affected by Parkinson's disease will continue to increase. This means the disease will become an even greater problem for modern societies due to the tremendous socio-economic costs associated," Dr Outeiro said. "It's therefore imperative that treatments for such neurodegenerative diseases are developed. Our studies in yeast have enabled us make a step towards this."
Sunday, September 5, 2010
How patients with dementia show improvement with music therapy
It’s been said that, “Music is a universal language”, and recent research with Dementia patients is proving that to be true; music can actually calm many patients and help to improve their memory!
Dementia causes many changes in the brain that can, in a sense, short-circuit the brain. Alzheimer’s and Dementia patients may begin to get lost in familiar surroundings, repeat questions, become fearful of their surroundings, suspicious of family members that they may not recognize. They may have trouble following directions and doing the simplest daily tasks. They can become disoriented about time, places and people around them. Simply bathing, brushing their teeth, using a fork or spoon or even swallowing are typically forgotten and patients will end up being fed, strictly with liquids through tubes. Eventually, daily care can require up to six or more caregivers per patient, which is why so many end up in nursing facilities, but life doesn’t have to be all misery for them.
With studies conducted in Belgium, Canada and the US, the findings are amazingly hopeful. We human beings seem to remember things that have emotional components. The parts of the brain, the Amygdala and our neurotransmitters, work together to help us recall the more emotional times that occur throughout our lives.
Petr Janata, a University of California, Associate Professor of Psychology, conducted brain activity experiments on a group of people who listened to music and found that the medial prefrontal cortex area of the brain stays healthier in Alzheimer’s patients longer than the other brain parts and has the capacity for emotions and other sensations.
According to, Concetta Tomaino, at the Institute for Music and Neurologic Function, at the Beth Abraham Health Services, in New York; we can recall audio very easily and the audio functions are often one of the last abilities that we lose. This seems to allow Alzheimer’s and Dementia patients to still have the capacity to sing songs of their youth, despite losing the capacity to recall many words, phrases and names. Documented research has shown that it can even extend to the more advanced cases of the disease.
Patients will often sing, hum and some even will begin to dance, despite the fact that minutes before they weren’t even speaking. Revisiting the music of earlier years can actually get these patients up and enjoying their day while even allowing them to have their memories stimulated; some patients recall the words to the songs even when they can’t recall their own family members’ names and faces. They were able to recall words and lyrics to many songs when hearing an audio recording than when they heard the lyrics spoken.
The music therapy often consists of CD’s being played, appropriate to the age range of the individuals or groups. Usually, the music that they either enjoyed as children, teens or young adults; sometimes, a discussion of many of the individual pieces and their association with movies or other shows can stimulate memories associated with better times or time spent with loved ones.
You can find CD’s, DVD’s and more at the local library that contain music familiar to the patients for whom you are caring. Familiar musicals, operas or Broadway show tunes can spark and open those mental trunks of long sealed away memories, giving many patients a memory boost and pleasure during their days.
Classical music has been proven, time and time again, to be soothing, so if you can play music for about an hour during the daytime or evening for those you care for, it will help to keep them calm and relaxed. Studies have shown that more than an hour can sometimes create agitation or irritability.
Playing an instrument, having a family sing-a-long can, as well and it allows some quality time with the family and friends that these patients wouldn’t otherwise be able to really enjoy.
These and other amazing studies are allowing many patients to stay calm, less agitated; it reduces anxiety and decreases wandering, may allow patients to improve some memory functions while enjoying their sing-a-long time reminiscing about the music that they grew up with. It can increase their socialization and decrease some depression which is of immense help to caregivers. Perhaps someday, music will help researchers to unlock the secrets to aiding these patients and their caregivers in having a more fulfilling life despite their disease.
by M. L. Kiser.
Dementia causes many changes in the brain that can, in a sense, short-circuit the brain. Alzheimer’s and Dementia patients may begin to get lost in familiar surroundings, repeat questions, become fearful of their surroundings, suspicious of family members that they may not recognize. They may have trouble following directions and doing the simplest daily tasks. They can become disoriented about time, places and people around them. Simply bathing, brushing their teeth, using a fork or spoon or even swallowing are typically forgotten and patients will end up being fed, strictly with liquids through tubes. Eventually, daily care can require up to six or more caregivers per patient, which is why so many end up in nursing facilities, but life doesn’t have to be all misery for them.
With studies conducted in Belgium, Canada and the US, the findings are amazingly hopeful. We human beings seem to remember things that have emotional components. The parts of the brain, the Amygdala and our neurotransmitters, work together to help us recall the more emotional times that occur throughout our lives.
Petr Janata, a University of California, Associate Professor of Psychology, conducted brain activity experiments on a group of people who listened to music and found that the medial prefrontal cortex area of the brain stays healthier in Alzheimer’s patients longer than the other brain parts and has the capacity for emotions and other sensations.
According to, Concetta Tomaino, at the Institute for Music and Neurologic Function, at the Beth Abraham Health Services, in New York; we can recall audio very easily and the audio functions are often one of the last abilities that we lose. This seems to allow Alzheimer’s and Dementia patients to still have the capacity to sing songs of their youth, despite losing the capacity to recall many words, phrases and names. Documented research has shown that it can even extend to the more advanced cases of the disease.
Patients will often sing, hum and some even will begin to dance, despite the fact that minutes before they weren’t even speaking. Revisiting the music of earlier years can actually get these patients up and enjoying their day while even allowing them to have their memories stimulated; some patients recall the words to the songs even when they can’t recall their own family members’ names and faces. They were able to recall words and lyrics to many songs when hearing an audio recording than when they heard the lyrics spoken.
The music therapy often consists of CD’s being played, appropriate to the age range of the individuals or groups. Usually, the music that they either enjoyed as children, teens or young adults; sometimes, a discussion of many of the individual pieces and their association with movies or other shows can stimulate memories associated with better times or time spent with loved ones.
You can find CD’s, DVD’s and more at the local library that contain music familiar to the patients for whom you are caring. Familiar musicals, operas or Broadway show tunes can spark and open those mental trunks of long sealed away memories, giving many patients a memory boost and pleasure during their days.
Classical music has been proven, time and time again, to be soothing, so if you can play music for about an hour during the daytime or evening for those you care for, it will help to keep them calm and relaxed. Studies have shown that more than an hour can sometimes create agitation or irritability.
Playing an instrument, having a family sing-a-long can, as well and it allows some quality time with the family and friends that these patients wouldn’t otherwise be able to really enjoy.
These and other amazing studies are allowing many patients to stay calm, less agitated; it reduces anxiety and decreases wandering, may allow patients to improve some memory functions while enjoying their sing-a-long time reminiscing about the music that they grew up with. It can increase their socialization and decrease some depression which is of immense help to caregivers. Perhaps someday, music will help researchers to unlock the secrets to aiding these patients and their caregivers in having a more fulfilling life despite their disease.
by M. L. Kiser.
Thursday, August 12, 2010
UC Parkinson's treatment shows promise
BY PEGGY O'FARRELL
Every morning, from about 8:30 to 10, Dan Truesdale froze up.
His muscles grew rigid, locked in place because of Parkinson's disease, until the medication finally kicked in, allowing to him get up, move around, live his life.
That changed last year when Truesdale, 47, became the first patient in Ohio to receive an experimental drug delivery system that gives his body a continual dose of the medication that lets him control his muscle movements.
His "frozen" muscles have thawed, Truesdale said.
"It's the best thing that's happened to me since I discovered I had Parkinson's," he said.
Researchers at the University of Cincinnati's Neuroscience Institute at University Hospital are recruiting more patients like Truesdale to test the system as part of a national phase 3 clinical trial.
Phase 3 trials are large-scale tests of new drugs or devices and the final step before federal health regulators decide to allow manufacturers to put new therapies on the market. Earlier phases test safety and effectiveness of new therapies on smaller scales.
Parkinson's disease is a chronic brain disorder in which brain cells that make the chemical dopamine die off. It usually strikes people over 50, and men are about 50 percent more likely to get it than women.
Without dopamine, adults lose control of muscle movements and balance. Symptoms get worse over time, said Alberto Espay, the neurologist heading up UC's arm of the trial, and Parkinson's patients may eventually lose the ability to speak, feed themselves, swallow or chew.
Replacing the lost dopamine helps patients regain muscle control, but standard treatments give dopamine in oral medications taken in several doses throughout the day.
That means the brain gets the dopamine it needs in interrupted allotments, so patients have periods throughout the day where they either can't move at all or they can't stop their bodies from moving involuntarily.
The drug delivery system Espay is testing aims to change that.
Abbott Pharmaceuticals' Levodopa-Carbidopa Intestinal Gel treatment system feeds the medication levodopa, which in the body becomes dopamine, into the upper intestine via a small tube surgically placed directly into the duodenum, or the very tip of the small intestine. The drug is fed through the tube from a cassette worn on the patient's body. A programmable pump lets the patient or doctor adjust the rate at which the medication is delivered.
"With this system, we're basically bathing the patient in dopamine at all times," Espay said.
Truesdale of Maineville used to be able to set his watch by his symptoms. The pump has changed all that. "I don't notice the passing of the hours because my symptoms have been reduced so drastically," he said.
He was diagnosed with Parkinson's in 2000, and has been on disability for the last four years. He recently began studying to become a minister.
The pump system is designed for patients like Truesdale with severe symptoms that are no longer controlled by standard medications, Espay said.
"People who've withdrawn from social and intellectual activities, they can resume them. We've seen people take up new activities after they've gone on the pump," he said.
Every morning, from about 8:30 to 10, Dan Truesdale froze up.
His muscles grew rigid, locked in place because of Parkinson's disease, until the medication finally kicked in, allowing to him get up, move around, live his life.
That changed last year when Truesdale, 47, became the first patient in Ohio to receive an experimental drug delivery system that gives his body a continual dose of the medication that lets him control his muscle movements.
His "frozen" muscles have thawed, Truesdale said.
"It's the best thing that's happened to me since I discovered I had Parkinson's," he said.
Researchers at the University of Cincinnati's Neuroscience Institute at University Hospital are recruiting more patients like Truesdale to test the system as part of a national phase 3 clinical trial.
Phase 3 trials are large-scale tests of new drugs or devices and the final step before federal health regulators decide to allow manufacturers to put new therapies on the market. Earlier phases test safety and effectiveness of new therapies on smaller scales.
Parkinson's disease is a chronic brain disorder in which brain cells that make the chemical dopamine die off. It usually strikes people over 50, and men are about 50 percent more likely to get it than women.
Without dopamine, adults lose control of muscle movements and balance. Symptoms get worse over time, said Alberto Espay, the neurologist heading up UC's arm of the trial, and Parkinson's patients may eventually lose the ability to speak, feed themselves, swallow or chew.
Replacing the lost dopamine helps patients regain muscle control, but standard treatments give dopamine in oral medications taken in several doses throughout the day.
That means the brain gets the dopamine it needs in interrupted allotments, so patients have periods throughout the day where they either can't move at all or they can't stop their bodies from moving involuntarily.
The drug delivery system Espay is testing aims to change that.
Abbott Pharmaceuticals' Levodopa-Carbidopa Intestinal Gel treatment system feeds the medication levodopa, which in the body becomes dopamine, into the upper intestine via a small tube surgically placed directly into the duodenum, or the very tip of the small intestine. The drug is fed through the tube from a cassette worn on the patient's body. A programmable pump lets the patient or doctor adjust the rate at which the medication is delivered.
"With this system, we're basically bathing the patient in dopamine at all times," Espay said.
Truesdale of Maineville used to be able to set his watch by his symptoms. The pump has changed all that. "I don't notice the passing of the hours because my symptoms have been reduced so drastically," he said.
He was diagnosed with Parkinson's in 2000, and has been on disability for the last four years. He recently began studying to become a minister.
The pump system is designed for patients like Truesdale with severe symptoms that are no longer controlled by standard medications, Espay said.
"People who've withdrawn from social and intellectual activities, they can resume them. We've seen people take up new activities after they've gone on the pump," he said.
Parkinson's Disease Placebo Response Increases with Expectations
Individuals with Parkinson's disease were more likely to have a neurochemical response to a placebo medication if they were told they had higher odds of receiving an active drug.
Chicago, IL - infoZine - "The promise of symptom improvement that is elicited by a placebo is a powerful modulator of brain neurochemistry," the authors write as background information to a report in the August issue of Archives of General Psychiatry, one of the JAMA/Archives journals. "Understanding the factors that modify the strength of the placebo effect is of major clinical as well as fundamental scientific significance." In patients with Parkinson's disease, the expectation of symptom improvement is associated with the release of the neurotransmitter dopamine, and the manipulation of this expectation has been shown to affect the motor performance of patients with the condition.
Sarah C. Lidstone, Ph.D., of Pacific Parkinson's Research Centre at Vancouver Coastal Health and the University of British Columbia, Vancouver, Canada, and colleagues studied 35 patients with mild to moderate Parkinson's disease undergoing treatment with the medication levodopa. On the first day of the study, a baseline positron emission tomographic (PET) scan was performed, participants were given levodopa and a second scan was performed one hour later to assess dopamine response. On the second day, patients were randomly assigned to one of four groups, during which they were told they had either a 25-percent, 50-percent, 75-percent or 100-percent chance of receiving active medication before the third scan; however, all patients were given placebo.
Patients who were told they had a 75-percent chance of receiving active medication demonstrated a significant release of dopamine in response to the placebo, whereas those in the other groups did not.
Patients' reactions to the active medication before the first scan was also correlated with their response to placebo. "Importantly, whereas prior medication experience (i.e., the dopaminergic response to levodopa) was the major determinant of dopamine release in the dorsal striatum, expectation of clinical improvement (i.e., the probability determined by group allocation) was additionally required to drive dopamine release in the ventral striatum," the authors write. Both areas have been shown to be involved with reward processing; in patients with a chronic debilitating illness who have responded to therapy in the past, expectation of therapeutic benefit in response to placebo has been likened to the expectation of receiving a reward.
"Our findings may have important implications for the design of clinical trials, as we have shown that both the probability of receiving active treatment—which varies in clinical trials depending on the study design and the information provided to the patient—as well as the treatment history of the patient influence dopamine system activity and consequently clinical outcome," the authors conclude. "While our finding of a biochemical placebo response restricted to a 75 percent likelihood of receiving active treatment may not generalize to diseases other than Parkinson's disease, it is extremely likely that both probability and prior experience have similarly profound effects in those conditions."
This study was funded by the Michael Smith Foundation for Health Research, the Canadian Institutes for Health Research and a TRIUMF Life Sciences Grant. Dr. Stoessl is supported by the Canada Research Chairs Program.
Chicago, IL - infoZine - "The promise of symptom improvement that is elicited by a placebo is a powerful modulator of brain neurochemistry," the authors write as background information to a report in the August issue of Archives of General Psychiatry, one of the JAMA/Archives journals. "Understanding the factors that modify the strength of the placebo effect is of major clinical as well as fundamental scientific significance." In patients with Parkinson's disease, the expectation of symptom improvement is associated with the release of the neurotransmitter dopamine, and the manipulation of this expectation has been shown to affect the motor performance of patients with the condition.
Sarah C. Lidstone, Ph.D., of Pacific Parkinson's Research Centre at Vancouver Coastal Health and the University of British Columbia, Vancouver, Canada, and colleagues studied 35 patients with mild to moderate Parkinson's disease undergoing treatment with the medication levodopa. On the first day of the study, a baseline positron emission tomographic (PET) scan was performed, participants were given levodopa and a second scan was performed one hour later to assess dopamine response. On the second day, patients were randomly assigned to one of four groups, during which they were told they had either a 25-percent, 50-percent, 75-percent or 100-percent chance of receiving active medication before the third scan; however, all patients were given placebo.
Patients who were told they had a 75-percent chance of receiving active medication demonstrated a significant release of dopamine in response to the placebo, whereas those in the other groups did not.
Patients' reactions to the active medication before the first scan was also correlated with their response to placebo. "Importantly, whereas prior medication experience (i.e., the dopaminergic response to levodopa) was the major determinant of dopamine release in the dorsal striatum, expectation of clinical improvement (i.e., the probability determined by group allocation) was additionally required to drive dopamine release in the ventral striatum," the authors write. Both areas have been shown to be involved with reward processing; in patients with a chronic debilitating illness who have responded to therapy in the past, expectation of therapeutic benefit in response to placebo has been likened to the expectation of receiving a reward.
"Our findings may have important implications for the design of clinical trials, as we have shown that both the probability of receiving active treatment—which varies in clinical trials depending on the study design and the information provided to the patient—as well as the treatment history of the patient influence dopamine system activity and consequently clinical outcome," the authors conclude. "While our finding of a biochemical placebo response restricted to a 75 percent likelihood of receiving active treatment may not generalize to diseases other than Parkinson's disease, it is extremely likely that both probability and prior experience have similarly profound effects in those conditions."
This study was funded by the Michael Smith Foundation for Health Research, the Canadian Institutes for Health Research and a TRIUMF Life Sciences Grant. Dr. Stoessl is supported by the Canada Research Chairs Program.
Saturday, July 24, 2010
UCSF Gene Therapy Method Allays Parkinson’s Symptoms
by Lauren Hammit
A novel technique created at UCSF to deliver a growth factor directly to brain cells has shown promising results in treating Parkinson’s symptoms and could enter human clinical trials as early as next year.
The technique is part of an experimental treatment called gene therapy, which is considered a hopeful medical advance for neurodegenerative diseases such as Parkinson’s. Gene therapy involves introducing genetic material into a cell to cause the expression of a particular protein that can replace a missing or defective protein responsible for disease.
The UCSF team demonstrated for the first time that the infusion system they designed successfully spread a targeted protein to critical regions in the primate brain. This resulted, on average, in a 50 percent improvement of symptoms that continued out to two years.
“The approach is among the first shown to be beneficial to animals after they have already developed signs of Parkinson’s,” said Krystof Bankiewicz, MD, PhD, Kinetics Foundation Chair in Translational Research and professor of Neurological Surgery at UCSF. “Our ultimate goal is to reverse this disease in patients, and we hope this method will enable doctors to do exactly that.”
Findings are published online and in the July 14, 2010, issue of the Journal of Neuroscience.
In addition to an improvement in Parkinson’s symptoms, the treated animals also maintained a higher density of neurons that produce the brain chemical dopamine – the same neurons that disappear in Parkinson’s disease. Live imaging of the brain by positron emission tomography (PET) scanning, which has been used to gauge treatment effects in clinical studies of Parkinson’s, showed that those neurons remained active.
“The scans enabled us to see where the protein went – and just as hoped, it had been taken up by neurons and transported along nerve fibers to where it was needed, the substantia nigra.” Bankiewicz said. Parkinson’s disease attacks the substantia nigra, which is a part of the brain that controls movement.
A clinical trial is planned to test the safety of the method, according to the National Institutes of Neurological Disorders and Stroke, which funded this research. In a workup for the trial, the National Institutes of Health Rapid Access to Interventional Development (NIH RAID) program is supporting additional toxicity studies, as well as the production of clinical grade virus.
A novel technique created at UCSF to deliver a growth factor directly to brain cells has shown promising results in treating Parkinson’s symptoms and could enter human clinical trials as early as next year.
The technique is part of an experimental treatment called gene therapy, which is considered a hopeful medical advance for neurodegenerative diseases such as Parkinson’s. Gene therapy involves introducing genetic material into a cell to cause the expression of a particular protein that can replace a missing or defective protein responsible for disease.
The UCSF team demonstrated for the first time that the infusion system they designed successfully spread a targeted protein to critical regions in the primate brain. This resulted, on average, in a 50 percent improvement of symptoms that continued out to two years.
“The approach is among the first shown to be beneficial to animals after they have already developed signs of Parkinson’s,” said Krystof Bankiewicz, MD, PhD, Kinetics Foundation Chair in Translational Research and professor of Neurological Surgery at UCSF. “Our ultimate goal is to reverse this disease in patients, and we hope this method will enable doctors to do exactly that.”
Findings are published online and in the July 14, 2010, issue of the Journal of Neuroscience.
In addition to an improvement in Parkinson’s symptoms, the treated animals also maintained a higher density of neurons that produce the brain chemical dopamine – the same neurons that disappear in Parkinson’s disease. Live imaging of the brain by positron emission tomography (PET) scanning, which has been used to gauge treatment effects in clinical studies of Parkinson’s, showed that those neurons remained active.
“The scans enabled us to see where the protein went – and just as hoped, it had been taken up by neurons and transported along nerve fibers to where it was needed, the substantia nigra.” Bankiewicz said. Parkinson’s disease attacks the substantia nigra, which is a part of the brain that controls movement.
A clinical trial is planned to test the safety of the method, according to the National Institutes of Neurological Disorders and Stroke, which funded this research. In a workup for the trial, the National Institutes of Health Rapid Access to Interventional Development (NIH RAID) program is supporting additional toxicity studies, as well as the production of clinical grade virus.
Saturday, July 17, 2010
Treatments and drugs
By Mayo Clinic staff
There's no cure for Parkinson's disease, but medications can help control some of the symptoms of Parkinson's disease, and in some case, surgery may be helpful. Your doctor may recommend lifestyle changes, such as physical therapy, a healthy diet and exercise, in addition to medications.
Medications
Medications can help manage problems with walking, movement and tremor by increasing the brain's supply of dopamine. However, taking dopamine itself is not helpful, because it's unable to enter your brain.
Your initial response to Parkinson's treatment can be dramatic. Over time, however, the benefits of drugs frequently diminish or become less consistent, although symptoms can usually still be fairly well controlled.
Examples of medication your doctor may prescribe include:
Levodopa. The most effective Parkinson's drug is levodopa, which is a natural substance in the body. When taken by mouth in pill form, it passes into the brain and is converted to dopamine. Levodopa is combined with carbidopa to create the combination drug, Sinemet. The carbidopa protects levodopa from premature conversion to dopamine outside the brain; in doing that, it also prevents nausea. In Europe, levodopa is combined with a similar substance, benserazide, and is marketed as Madopar.
As the disease progresses, the benefit from levodopa may become less stable, with a tendency to wax and wane ("wearing off"). This then requires medication adjustments. Levodopa side effects include involuntary movements called dyskinesia. These resolve with dose reduction, but sometimes at the expense of reduced parkinsonism control. Like other Parkinson's drugs, it may also lower your blood pressure when standing.
Dopamine agonists. Unlike levodopa, these drugs aren't changed into dopamine. Instead, they mimic the effects of dopamine in the brain and cause neurons to react as though dopamine is present. They are not nearly as effective in treating the symptoms of Parkinson's disease. However, they last longer and are often used to smooth the sometimes off-and-on effect of levodopa.
This class includes pill forms of dopamine agonists, such as pramipexole (Mirapex) and ropinirole (Requip). A short-acting injectable dopamine agonist, apomorphine (Apokyn), is used for quick relief.
The side effects of dopamine agonists include hallucinations, sleepiness, water retention and low blood pressure when standing. These medications may also increase your risk of compulsive behaviors such as hypersexuality, compulsive gambling and compulsive overeating. If you are taking these medications and start behaving in a way that's out of character for you, talk to your doctor.
* MAO B inhibitors. These types of drugs, including selegiline (Eldepryl) and rasagiline (Azilect), help prevent the breakdown of both naturally occurring dopamine and dopamine formed from levodopa. They do this by inhibiting the activity of the enzyme monoamine oxidase B (MAO B) — an enzyme that metabolizes dopamine in the brain. Side effects are rare but may include confusion, headache, hallucinations and dizziness. These medications can't be used in combination with other antidepressants, the antibiotic ciprofloxacin (Cipro), the herb St. John's wort or certain narcotics. Check with your doctor before taking any additional medications with an MAO inhibitor.
* Catechol O-methyltransferase (COMT) inhibitors. These drugs prolong the effect of carbidopa-levodopa therapy by blocking an enzyme that breaks down levodopa. Tolcapone (Tasmar) has been linked to liver damage and liver failure, so it's normally used only in people who aren't responding to other therapies. Entacapone (Comtan) doesn't cause liver problems and is now combined with carbidopa and levodopa in a medication called Stalevo. However, it may worsen other levodopa side effects, such as involuntary movements (dyskinesias), nausea, confusion or hallucinations. It may cause urine discoloration.
* Anticholinergics. These drugs have been used for many years to help control the tremor associated with Parkinson's disease. A number of anticholinergic drugs, such as benztropine (Cogentin) and trihexyphenidyl, are available. However, their modest benefits are often offset by side effects such as impaired memory, confusion, constipation, dry mouth and eyes, and impaired urination.
* Glutamate (NMDA) blocking drugs. Doctors may prescribe amantadine (Symmetrel) alone to provide short-term relief of mild, early-stage Parkinson's disease. It also may be added to carbidopa-levodopa therapy for people in the later stages of Parkinson's disease, especially if they have problems with involuntary movements (dyskinesia) induced by carbidopa-levodopa. Side effects include a purple mottling of the skin and, sometimes, hallucinations.
Physical therapy
Exercise is important for general health, but especially for maintaining function in Parkinson's disease. Physical therapy may be advisable and can help improve your mobility, range of motion and muscle tone. Although specific exercises can't stop the progress of the disease, maintaining muscle strength and agility can help counter some of the progressive tendencies of the disease and also allow you to feel more confident and capable. A physical therapist can also work with you to improve your gait and balance. A speech therapist or speech pathologist can improve problems with speaking and swallowing.
Surgery
Deep brain stimulation is a surgical procedure used to treat Parkinson's disease. It involves implanting an electrode deep within the parts of your brain that control movement. The amount of stimulation delivered by the electrode is controlled by a pacemaker-like device placed under the skin in your upper chest. A wire that travels under your skin connects the device, called a pulse generator, to the electrodes.
Deep brain stimulation is most often used for people with advanced Parkinson's disease who have unstable medication (levodopa) responses. It can stabilize medication fluctuations and reduce or eliminate involuntary movements (dyskinesia). Tremor is especially responsive to this therapy.
Serious risks of this procedure are uncommon, but include brain hemorrhage or stroke. Infection is also a risk, and sometimes requires parts of the device to be replaced. Deep brain stimulation isn't beneficial for people who don't respond to carbidopa-levodopa.
There's no cure for Parkinson's disease, but medications can help control some of the symptoms of Parkinson's disease, and in some case, surgery may be helpful. Your doctor may recommend lifestyle changes, such as physical therapy, a healthy diet and exercise, in addition to medications.
Medications
Medications can help manage problems with walking, movement and tremor by increasing the brain's supply of dopamine. However, taking dopamine itself is not helpful, because it's unable to enter your brain.
Your initial response to Parkinson's treatment can be dramatic. Over time, however, the benefits of drugs frequently diminish or become less consistent, although symptoms can usually still be fairly well controlled.
Examples of medication your doctor may prescribe include:
Levodopa. The most effective Parkinson's drug is levodopa, which is a natural substance in the body. When taken by mouth in pill form, it passes into the brain and is converted to dopamine. Levodopa is combined with carbidopa to create the combination drug, Sinemet. The carbidopa protects levodopa from premature conversion to dopamine outside the brain; in doing that, it also prevents nausea. In Europe, levodopa is combined with a similar substance, benserazide, and is marketed as Madopar.
As the disease progresses, the benefit from levodopa may become less stable, with a tendency to wax and wane ("wearing off"). This then requires medication adjustments. Levodopa side effects include involuntary movements called dyskinesia. These resolve with dose reduction, but sometimes at the expense of reduced parkinsonism control. Like other Parkinson's drugs, it may also lower your blood pressure when standing.
Dopamine agonists. Unlike levodopa, these drugs aren't changed into dopamine. Instead, they mimic the effects of dopamine in the brain and cause neurons to react as though dopamine is present. They are not nearly as effective in treating the symptoms of Parkinson's disease. However, they last longer and are often used to smooth the sometimes off-and-on effect of levodopa.
This class includes pill forms of dopamine agonists, such as pramipexole (Mirapex) and ropinirole (Requip). A short-acting injectable dopamine agonist, apomorphine (Apokyn), is used for quick relief.
The side effects of dopamine agonists include hallucinations, sleepiness, water retention and low blood pressure when standing. These medications may also increase your risk of compulsive behaviors such as hypersexuality, compulsive gambling and compulsive overeating. If you are taking these medications and start behaving in a way that's out of character for you, talk to your doctor.
* MAO B inhibitors. These types of drugs, including selegiline (Eldepryl) and rasagiline (Azilect), help prevent the breakdown of both naturally occurring dopamine and dopamine formed from levodopa. They do this by inhibiting the activity of the enzyme monoamine oxidase B (MAO B) — an enzyme that metabolizes dopamine in the brain. Side effects are rare but may include confusion, headache, hallucinations and dizziness. These medications can't be used in combination with other antidepressants, the antibiotic ciprofloxacin (Cipro), the herb St. John's wort or certain narcotics. Check with your doctor before taking any additional medications with an MAO inhibitor.
* Catechol O-methyltransferase (COMT) inhibitors. These drugs prolong the effect of carbidopa-levodopa therapy by blocking an enzyme that breaks down levodopa. Tolcapone (Tasmar) has been linked to liver damage and liver failure, so it's normally used only in people who aren't responding to other therapies. Entacapone (Comtan) doesn't cause liver problems and is now combined with carbidopa and levodopa in a medication called Stalevo. However, it may worsen other levodopa side effects, such as involuntary movements (dyskinesias), nausea, confusion or hallucinations. It may cause urine discoloration.
* Anticholinergics. These drugs have been used for many years to help control the tremor associated with Parkinson's disease. A number of anticholinergic drugs, such as benztropine (Cogentin) and trihexyphenidyl, are available. However, their modest benefits are often offset by side effects such as impaired memory, confusion, constipation, dry mouth and eyes, and impaired urination.
* Glutamate (NMDA) blocking drugs. Doctors may prescribe amantadine (Symmetrel) alone to provide short-term relief of mild, early-stage Parkinson's disease. It also may be added to carbidopa-levodopa therapy for people in the later stages of Parkinson's disease, especially if they have problems with involuntary movements (dyskinesia) induced by carbidopa-levodopa. Side effects include a purple mottling of the skin and, sometimes, hallucinations.
Physical therapy
Exercise is important for general health, but especially for maintaining function in Parkinson's disease. Physical therapy may be advisable and can help improve your mobility, range of motion and muscle tone. Although specific exercises can't stop the progress of the disease, maintaining muscle strength and agility can help counter some of the progressive tendencies of the disease and also allow you to feel more confident and capable. A physical therapist can also work with you to improve your gait and balance. A speech therapist or speech pathologist can improve problems with speaking and swallowing.
Surgery
Deep brain stimulation is a surgical procedure used to treat Parkinson's disease. It involves implanting an electrode deep within the parts of your brain that control movement. The amount of stimulation delivered by the electrode is controlled by a pacemaker-like device placed under the skin in your upper chest. A wire that travels under your skin connects the device, called a pulse generator, to the electrodes.
Deep brain stimulation is most often used for people with advanced Parkinson's disease who have unstable medication (levodopa) responses. It can stabilize medication fluctuations and reduce or eliminate involuntary movements (dyskinesia). Tremor is especially responsive to this therapy.
Serious risks of this procedure are uncommon, but include brain hemorrhage or stroke. Infection is also a risk, and sometimes requires parts of the device to be replaced. Deep brain stimulation isn't beneficial for people who don't respond to carbidopa-levodopa.
Saturday, July 10, 2010
Top Ten Things to Know About Stem Cell Treatments
by Juan Munevar
There are different types of stem cells—each with their own purpose.
There are many different types of stem cells that come from different places in the body or are formed at different times in our lives. These include embryonic stem cells that exist only at the earliest stages of development and various types of ‘tissue-specific’ or ‘adult’ stem cells that appear during fetal development and remain in our bodies throughout life.
Our bodies use different types of tissue-specific stem cells to fit a particular purpose. Tissue-specific stem cells are limited in their potential and largely make the cell types found in the tissue from which they are derived. For example, the blood-forming stem cells (or hematopoietic stem cells) in the bone marrow regenerate the blood, while neural stem cells in the brain make brain cells. A neural stem cell won’t spontaneously make a blood cell and likewise a hematopoietic stem cell won’t spontaneously make a brain cell. Thus, it is unlikely that a single cell type could be used to treat a multitude of unrelated diseases that involve different tissues or organs. Be wary of clinics that offer treatments with stem cells that originate from a part of the body that is different from the part being treated.
2. A single stem cell treatment will not work on a multitude of unrelated diseases or conditions.
As described above, each type of stem cell fulfills a specific function in the body and cannot be expected to make cell types from other tissues. Thus, it is unlikely that a single type of stem cell treatment can treat multiple unrelated conditions, such as diabetes and Parkinson’s disease. The underlying causes are very different and different cell types would need to be replaced to treat each condition. It is critical that the cell type used as a treatment be appropriate to the specific disease or condition.
Embryonic stem cells may one day be used to generate treatments for a range of human diseases. However, embryonic stem cells themselves cannot directly be used for therapies as they would likely cause tumors and are unlikely to become the cells needed to regenerate a tissue on their own. They would first need to be coaxed to develop into specialized cell types before transplantation. A major warning sign that a clinic may not be credible is when treatments are offered for a wide variety of conditions but rely on a single cell type.
3. Currently, there are very few widely accepted stem cell therapies.
The range of diseases where stem cell treatments have been shown to be beneficial in responsibly conducted clinical trials is still extremely restricted. The best defined and most extensively used is blood stem cell transplantation to treat diseases and conditions of the blood and immune system, or to restore the blood system after treatments for specific cancers. Some bone, skin and corneal diseases or injuries can be treated with grafting of tissue that depends upon stem cells from these organs. These therapies are also generally accepted as safe and effective by the medical community.
4. Just because people say stem cells helped them doesn’t mean they did.
There are three main reasons why a person might feel better that are unrelated to the actual stem cell treatment: the ‘placebo effect’, accompanying treatments, and natural fluctuations of the disease or condition. The intense desire or belief that a treatment will work can cause a person to feel like it has and to even experience positive physical changes, such as improved movement or less pain. This phenomenon is called the placebo effect. Even having a positive conversation with a doctor can cause a person to feel improvement. Likewise, other techniques offered along with stem cell treatment—such as changes to diet, relaxation, physical therapy, medication, etc.—may make a person feel better in a way that is unrelated to the stem cells. Also, the severity of symptoms of many conditions can change over time, resulting in either temporary improvement or decline, which can complicate the interpretation of the effectiveness of treatments. These factors are so widespread that without testing in a controlled clinical study, where a group that receives a treatment is carefully compared against a group that does not receive this treatment, it is very difficult to determine the real effect of any therapy. Be wary of clinics that measure or advertise their results primarily through patient testimonials.
5. A large part of why it takes time to develop new therapies is that science itself is a long and difficult process.
Science, in general, is a long and involved process. Understanding what goes wrong in disease or injury and how to fix it takes time. New ideas have to be tested first in a research laboratory, and many times the new ideas don’t work. Even once the basic science has been established, translating it into an effective medical treatment is a long and difficult process. Something that looks promising in cultured cells may fail as a therapy in an animal model and something that works in an animal model may fail when it is tried on humans. Once therapies are tested in humans, ensuring patient safety becomes a critical issue and this means starting with very few people until the safety and side effects are better understood.
6. To be used in treatments, stem cells will have to be instructed to behave in specific ways.
Bone marrow transplantation is typically successful because we are asking the cells to do exactly what they were designed to do, make more blood. For other conditions, we may want the cells to behave in ways that are different from how they would ordinarily work in the body. One of the greatest barriers to the development of successful stem cell therapies is to get the cells to behave in the desired way. Also, once transplanted inside the body the cells need to integrate and function in concert with the body’s other cells. For example, to treat many neurological conditions the cells we implant will need to grow into specific types of neurons, and to work they will also have to know which other neurons to make connections with and how to make these connections. We are still learning about how to direct stem cells to become the right cell type, to grow only as much as we need them to, and the best ways to transplant them. Discovering how to do all this will take time. Be wary of claims that stem cells will somehow just know where to go and what to do to treat a specific condition.
7. Just because stem cells came from your body doesn’t mean they are safe.
Every medical procedure has risks. While you are unlikely to have an immune response to your own cells, the procedures used to acquire, grow and deliver them are potentially risky. As soon as the cells leave your body they may be subjected to a number of manipulations that could change the characteristics of the cells. If they are grown in culture (a process called expansion), the cells may lose the normal mechanisms that control growth or may lose the ability to specialize into the cell types you need. The cells may become contaminated with bacteria, viruses or other pathogens that could cause disease. The procedure to either remove or inject the cells also carries risk, from introducing an infection to damaging the tissue into which they are injected.
8. There is something to lose by trying an unproven treatment.
Some of the conditions that clinics claim are treatable with stem cells are considered incurable by other means. It is easy to understand why people might feel they have nothing to lose from trying something even if it is unproven. However, there are very real risks of developing complications, both immediate and long-term, while the chance of experiencing a benefit is likely very low. In one publicized case, a young boy developed brain tumors as a result of a stem cell treatment. Participating in an unproven treatment may make a person ineligible to participate in upcoming clinical trials (see also number 9). Where cost is high, there may be long-term financial implications for patients, their families and communities. If travel is involved there are additional considerations, not the least of which is being away from family and friends.
9. An experimental treatment offered for sale is not the same as a clinical trial.
The fact that a procedure is experimental does not automatically mean that it is part of a research study or clinical trial. A responsible clinical trial can be characterized by a number of key features. There is preclinical data supporting that the treatment being tested is likely to be safe and effective. Before starting, there is oversight by an independent group such as an Institutional Review Board or medical ethics committee that protect patients’ rights, and in many countries the trial is assessed and approved by a national regulatory agency, such as the European Medicines Agency (EMA) or the U.S. Food and Drug Administration (FDA). The study itself is designed to answer specific questions about a new treatment or a new way of using current treatments, often with a control group to which the group of people receiving the new treatment is compared. Typically, the cost of the new treatment and trial monitoring is defrayed by the company developing the treatment or by local or national government funding. Beware of expensive treatments that have not passed successfully through clinical trials.
Responsibly-conducted clinical trials are critical to the development of new treatments as they allow us to learn whether these treatments are safe and effective. The ISSCR supports participation in responsible clinical trials after careful consideration of the issues highlighted on this site and in discussion with a trusted physician.
10. Stem cell science is constantly moving forward.
Stem cell science is extraordinarily promising. There have been great advances in treating diseases and conditions of the blood system using blood-forming stem cells, and these show us just how powerful stem cell therapies can be. Scientists all over the world are researching ways to harness stem cells and use them to learn more about, to diagnose, and to treat various diseases and conditions. Every day scientists are working on new ways to shape and control different types of stem cells in ways that are bringing us closer to developing new treatments. Many potential treatments are currently being tested in animal models and some have already been brought to clinical trials. In February 2010 the British company ReNeuron announced it had been approved to conduct a Phase I clinical trial of a neural stem cell treatment for stroke. The first embryonic stem cell-based treatment for acute spinal cord injury is currently under review by the U.S. Food and Drug Administration (FDA) and will hopefully move into clinical trials soon. Although it is sometimes hard to see, stem cell science is moving forward. We are tremendously optimistic that stem cell therapies will someday be available to treat a wide range of human diseases and conditions.
There are different types of stem cells—each with their own purpose.
There are many different types of stem cells that come from different places in the body or are formed at different times in our lives. These include embryonic stem cells that exist only at the earliest stages of development and various types of ‘tissue-specific’ or ‘adult’ stem cells that appear during fetal development and remain in our bodies throughout life.
Our bodies use different types of tissue-specific stem cells to fit a particular purpose. Tissue-specific stem cells are limited in their potential and largely make the cell types found in the tissue from which they are derived. For example, the blood-forming stem cells (or hematopoietic stem cells) in the bone marrow regenerate the blood, while neural stem cells in the brain make brain cells. A neural stem cell won’t spontaneously make a blood cell and likewise a hematopoietic stem cell won’t spontaneously make a brain cell. Thus, it is unlikely that a single cell type could be used to treat a multitude of unrelated diseases that involve different tissues or organs. Be wary of clinics that offer treatments with stem cells that originate from a part of the body that is different from the part being treated.
2. A single stem cell treatment will not work on a multitude of unrelated diseases or conditions.
As described above, each type of stem cell fulfills a specific function in the body and cannot be expected to make cell types from other tissues. Thus, it is unlikely that a single type of stem cell treatment can treat multiple unrelated conditions, such as diabetes and Parkinson’s disease. The underlying causes are very different and different cell types would need to be replaced to treat each condition. It is critical that the cell type used as a treatment be appropriate to the specific disease or condition.
Embryonic stem cells may one day be used to generate treatments for a range of human diseases. However, embryonic stem cells themselves cannot directly be used for therapies as they would likely cause tumors and are unlikely to become the cells needed to regenerate a tissue on their own. They would first need to be coaxed to develop into specialized cell types before transplantation. A major warning sign that a clinic may not be credible is when treatments are offered for a wide variety of conditions but rely on a single cell type.
3. Currently, there are very few widely accepted stem cell therapies.
The range of diseases where stem cell treatments have been shown to be beneficial in responsibly conducted clinical trials is still extremely restricted. The best defined and most extensively used is blood stem cell transplantation to treat diseases and conditions of the blood and immune system, or to restore the blood system after treatments for specific cancers. Some bone, skin and corneal diseases or injuries can be treated with grafting of tissue that depends upon stem cells from these organs. These therapies are also generally accepted as safe and effective by the medical community.
4. Just because people say stem cells helped them doesn’t mean they did.
There are three main reasons why a person might feel better that are unrelated to the actual stem cell treatment: the ‘placebo effect’, accompanying treatments, and natural fluctuations of the disease or condition. The intense desire or belief that a treatment will work can cause a person to feel like it has and to even experience positive physical changes, such as improved movement or less pain. This phenomenon is called the placebo effect. Even having a positive conversation with a doctor can cause a person to feel improvement. Likewise, other techniques offered along with stem cell treatment—such as changes to diet, relaxation, physical therapy, medication, etc.—may make a person feel better in a way that is unrelated to the stem cells. Also, the severity of symptoms of many conditions can change over time, resulting in either temporary improvement or decline, which can complicate the interpretation of the effectiveness of treatments. These factors are so widespread that without testing in a controlled clinical study, where a group that receives a treatment is carefully compared against a group that does not receive this treatment, it is very difficult to determine the real effect of any therapy. Be wary of clinics that measure or advertise their results primarily through patient testimonials.
5. A large part of why it takes time to develop new therapies is that science itself is a long and difficult process.
Science, in general, is a long and involved process. Understanding what goes wrong in disease or injury and how to fix it takes time. New ideas have to be tested first in a research laboratory, and many times the new ideas don’t work. Even once the basic science has been established, translating it into an effective medical treatment is a long and difficult process. Something that looks promising in cultured cells may fail as a therapy in an animal model and something that works in an animal model may fail when it is tried on humans. Once therapies are tested in humans, ensuring patient safety becomes a critical issue and this means starting with very few people until the safety and side effects are better understood.
6. To be used in treatments, stem cells will have to be instructed to behave in specific ways.
Bone marrow transplantation is typically successful because we are asking the cells to do exactly what they were designed to do, make more blood. For other conditions, we may want the cells to behave in ways that are different from how they would ordinarily work in the body. One of the greatest barriers to the development of successful stem cell therapies is to get the cells to behave in the desired way. Also, once transplanted inside the body the cells need to integrate and function in concert with the body’s other cells. For example, to treat many neurological conditions the cells we implant will need to grow into specific types of neurons, and to work they will also have to know which other neurons to make connections with and how to make these connections. We are still learning about how to direct stem cells to become the right cell type, to grow only as much as we need them to, and the best ways to transplant them. Discovering how to do all this will take time. Be wary of claims that stem cells will somehow just know where to go and what to do to treat a specific condition.
7. Just because stem cells came from your body doesn’t mean they are safe.
Every medical procedure has risks. While you are unlikely to have an immune response to your own cells, the procedures used to acquire, grow and deliver them are potentially risky. As soon as the cells leave your body they may be subjected to a number of manipulations that could change the characteristics of the cells. If they are grown in culture (a process called expansion), the cells may lose the normal mechanisms that control growth or may lose the ability to specialize into the cell types you need. The cells may become contaminated with bacteria, viruses or other pathogens that could cause disease. The procedure to either remove or inject the cells also carries risk, from introducing an infection to damaging the tissue into which they are injected.
8. There is something to lose by trying an unproven treatment.
Some of the conditions that clinics claim are treatable with stem cells are considered incurable by other means. It is easy to understand why people might feel they have nothing to lose from trying something even if it is unproven. However, there are very real risks of developing complications, both immediate and long-term, while the chance of experiencing a benefit is likely very low. In one publicized case, a young boy developed brain tumors as a result of a stem cell treatment. Participating in an unproven treatment may make a person ineligible to participate in upcoming clinical trials (see also number 9). Where cost is high, there may be long-term financial implications for patients, their families and communities. If travel is involved there are additional considerations, not the least of which is being away from family and friends.
9. An experimental treatment offered for sale is not the same as a clinical trial.
The fact that a procedure is experimental does not automatically mean that it is part of a research study or clinical trial. A responsible clinical trial can be characterized by a number of key features. There is preclinical data supporting that the treatment being tested is likely to be safe and effective. Before starting, there is oversight by an independent group such as an Institutional Review Board or medical ethics committee that protect patients’ rights, and in many countries the trial is assessed and approved by a national regulatory agency, such as the European Medicines Agency (EMA) or the U.S. Food and Drug Administration (FDA). The study itself is designed to answer specific questions about a new treatment or a new way of using current treatments, often with a control group to which the group of people receiving the new treatment is compared. Typically, the cost of the new treatment and trial monitoring is defrayed by the company developing the treatment or by local or national government funding. Beware of expensive treatments that have not passed successfully through clinical trials.
Responsibly-conducted clinical trials are critical to the development of new treatments as they allow us to learn whether these treatments are safe and effective. The ISSCR supports participation in responsible clinical trials after careful consideration of the issues highlighted on this site and in discussion with a trusted physician.
10. Stem cell science is constantly moving forward.
Stem cell science is extraordinarily promising. There have been great advances in treating diseases and conditions of the blood system using blood-forming stem cells, and these show us just how powerful stem cell therapies can be. Scientists all over the world are researching ways to harness stem cells and use them to learn more about, to diagnose, and to treat various diseases and conditions. Every day scientists are working on new ways to shape and control different types of stem cells in ways that are bringing us closer to developing new treatments. Many potential treatments are currently being tested in animal models and some have already been brought to clinical trials. In February 2010 the British company ReNeuron announced it had been approved to conduct a Phase I clinical trial of a neural stem cell treatment for stroke. The first embryonic stem cell-based treatment for acute spinal cord injury is currently under review by the U.S. Food and Drug Administration (FDA) and will hopefully move into clinical trials soon. Although it is sometimes hard to see, stem cell science is moving forward. We are tremendously optimistic that stem cell therapies will someday be available to treat a wide range of human diseases and conditions.
Tuesday, June 22, 2010
Report: Spine Stimulation May Benefit Parkinson’s Disease Patients
By Steven Marsh
Patients who have been diagnosed with Parkinson’s disease (PD) may have relief from symptoms associated with the condition in the near future, according to a study presented at the 2010 American Society for Stereotactical and Functional Neurosurgery.
In an effort to find potential treatments for individuals with the nervous system disorder, a team of researchers at Rhode Island Hospital conducted a series of exercises that stimulated the spinal cord on an animal model, which showed signs of PD. Because the findings displayed better motor function in the animal, the investigators tested the treatment with spinal cord simulation on a male patient aged 82 years.
While the individual wasn’t receiving any form of medication as treatment for the disorder, researchers used different frequencies of stimulation to determine if a human would experience similar results compared to the animal model.
The researchers discovered that high stimulation frequencies made it easier for the patient to walk, while low frequencies worsened PD side effects.
While the results of the study did give investigators some insight as to how to treat PD patients, clinical trials with a larger group of patients would be more beneficial to developing treatment.
Finding therapies for this disorder is growing in interest throughout the medical world, as QR Pharma and Massachusetts General Hospital have launched research to determine a way to block a protein associated the development of PD.ADNFCR-1960-ID-19845071-ADNFCR
Patients who have been diagnosed with Parkinson’s disease (PD) may have relief from symptoms associated with the condition in the near future, according to a study presented at the 2010 American Society for Stereotactical and Functional Neurosurgery.
In an effort to find potential treatments for individuals with the nervous system disorder, a team of researchers at Rhode Island Hospital conducted a series of exercises that stimulated the spinal cord on an animal model, which showed signs of PD. Because the findings displayed better motor function in the animal, the investigators tested the treatment with spinal cord simulation on a male patient aged 82 years.
While the individual wasn’t receiving any form of medication as treatment for the disorder, researchers used different frequencies of stimulation to determine if a human would experience similar results compared to the animal model.
The researchers discovered that high stimulation frequencies made it easier for the patient to walk, while low frequencies worsened PD side effects.
While the results of the study did give investigators some insight as to how to treat PD patients, clinical trials with a larger group of patients would be more beneficial to developing treatment.
Finding therapies for this disorder is growing in interest throughout the medical world, as QR Pharma and Massachusetts General Hospital have launched research to determine a way to block a protein associated the development of PD.ADNFCR-1960-ID-19845071-ADNFCR
Thursday, June 10, 2010
The Pharmacist's Perspective on Treatment of Early-Stage Parkinson's Disease
Jack J. Chen, PharmD, BCPS, CGP
The management of Parkinson's disease (PD) is complex and involves nonpharmacologic and pharmacologic interventions for motor and nonmotor symptoms (see accompanying article by Dr. Simuni). The aim of this article is to provide a greater understanding of PD, treatment risks and benefits, and new developments in treatment approach that will allow clinicians, pharmacists, and allied healthcare personnel to better educate and care for patients with PD.
As PD progresses from early to advanced stages, medication adjustments and increased numbers of medications should be expected. This article will focus on pharmacotherapy interventions for early-stage PD with an emphasis on safety and drug interactions. A discussion about early interventions in PD, outcomes, and healthcare costs is available elsewhere.[1] Discussions regarding advanced stage PD, management of motor complications, and pharmacotherapies for nonmotor symptoms of PD are beyond the scope of this article and are also available elsewhere.[2]
The Patient With Early-Stage PD
An individual with early-stage PD who has been recently diagnosed may present with motor symptoms and absence of functional impairment or mild functional impairment (eg, clumsiness of the hands, mild deterioration in performance of sports activities, a bothersome tremor, worsening of handwriting). An untreated patient with early-stage PD will have a Unified Parkinson's Disease Rating Scale (UPDRS) score of 20 to 30.
The current pharmacologic management paradigm for early-stage PD consists of initiating 1 drug (ie, monotherapy) to provide symptomatic benefit. Drug therapy is typically initiated to address functional impairment. However, with the publication of the Attenuation of Disease progression with Azilect Given Once-daily (ADAGIO) study data, initiation of rasagiline in recently diagnosed patients with early PD presenting without functional impairment is a plausible approach.
In early-stage PD, monoamine oxidase type B (MAO-B) inhibitors, dopamine agonists, and levodopa (with a decarboxylase inhibitor such as carbidopa) all provide a sufficient magnitude of therapeutic effect. In addition to providing relief of tremor, rigidity, and/or slowness of movement, pharmacotherapy can also improve nonmotor symptoms such as fatigue in early PD and can improve experiences of daily living. If other symptoms such as constipation, depression, sexual dysfunction, and sleep disorders are present, adjunctive therapies that specifically target the symptom should also be considered.
Pharmacotherapy for Early-Stage PD: Safety, Side Effects, Drug Interactions
Drug safety and treatment-emergent side effects play a major role in guiding the selection and adjustment of pharmacotherapy in PD. Healthcare professionals involved in the pharmacotherapy management and distribution spectrum of PD should be concerned about the overall safety of the medications in this population, the safety of polypharmacy regimens and their necessity (or lack thereof), drug interactions, and education of the patient and family about benefits and risks of the medication regimen. Pharmacists, in particular, are traditionally more focused on drug safety and interactions as well as on providing instructions on proper use of medications.
Levodopa
Levodopa provides a robust magnitude of symptom relief effects. In patients with early PD, common side effects of levodopa include nausea and somnolence. Of note, hallucinations and psychosis are more common in patients with advanced stage PD. There is concern about the gradual emergence of motor complications (such as dyskinesias and fluctuations) associated with dose escalation and treatment duration. Motor complications can arise quickly (within a few months) or slowly (after a year or more). Although there are risk factors (eg, levodopa dose and treatment duration, younger age), no method has been found to predict which patients will experience motor complications.
The development of levodopa-associated motor complications has a significant impact on clinicians, patients, and healthcare resources. Motor complications can be a challenge for clinicians to manage, can impair patient health-related quality of life, and can increase direct health costs. Independent researchers and pharmaceutical manufacturers have devoted time and resources toward understanding the pathophysiology of motor complications and developing interventions that have specific efficacy for motor complications (eg, apomorphine, entacapone, rasagiline, selegiline oral disintegrating tablets, and deep brain stimulation). Eventually all patients with PD will be prescribed levodopa; however, in patients with early PD, other medications are available to provide adequate symptom relief without the risk for motor complications.
Pramipexole, ropinirole, and rasagiline are also indicated as monotherapy for PD. Clinicians and patients should engage in discussions about the relative risks and benefits of levodopa therapy, and patients should be allowed to make informed decisions.
Dopamine Agonists
The dopamine agonists (pramipexole, ropinirole) provide sufficient symptomatic effects for patients with early-stage PD and are less likely to cause motor complications. Side effects that are encountered by patients with early PD include nausea, somnolence, edema of the extremities, orthostatic hypotension, and impulse control disorders (ICDs). Of note, hallucinations may occur in patients with early PD, but are more common in advanced stage PD or patients with cognitive impairment.
Postmarketing recognition of the potential for dopamine agonist-induced ICDs has attracted much concern among clinicians who treat PD. ICDs can be a source of financial and familial strain for the patient. Common examples include excessive gambling, preoccupation with pornography, overindulgence in purchasing unnecessary items, excessive hobbyism, and preoccupation with Internet activities. The prospect of this potentially disruptive side effect should be communicated to the patient and family. Dopamine agonist-associated ICDs are not dose related and can also develop in patients receiving low daily doses for restless legs syndrome.
MAO-B Inhibitors
The MAO-B inhibitors (rasagiline, selegiline) provide modest symptomatic relief in patients with early PD. Of the available MAO-B inhibitors, rasagiline is the only one with labeling approved by the US Food and Drug Administration for monotherapy in PD. In addition, data from the ADAGIO study (a large, randomized, controlled trial) suggest that early initiation of rasagiline in patients with PD and the absence of functional impairment confer more benefit than delaying therapy.
Rasagiline is well tolerated in patients with early PD. Treatment-emergent side effects are nonspecific and include flulike weakness and asthenia. Overall, rasagiline is notable for its lack of dopaminergic side effects (eg, nausea, orthostasis, somnolence). Postmarketing data indicate that rasagiline can be safely administered without regard to meal content of tyramine (eg, in foods such as aged cheeses, red wine, sauerkraut). Based on clinical pharmacology studies, tyramine restriction is no longer required or advocated by the FDA when rasagiline is initiated. Likewise, sympathomimetic amines (eg, ephedrine, phenylephrine, phenylpropanolamine, pseudoephedrine) and local anesthesia with sympathomimetic vasoconstrictors can be administered concomitantly. Although the concurrent use of antidepressants (with serotonergic activity) is not contraindicated, benefits should be weighed against the potential for serotonin syndrome. The STACCATO study is underway to better define the potential occurrence of serotonin syndrome with rasagiline and antidepressants.[3]
Patient and Family Education
Patient and family education is critical for the safe and successful use of medications in patients with PD. The patient/family should be counseled about the adverse effects that are most likely to occur and when to report them to the prescriber. For example, ICDs such as Internet gambling could go undetected by family and unreported by patients and result in serious financial complications. Nausea, common with levodopa and dopamine agonists, is uncomfortable for patients, and in some circumstances, may cause discontinuation of therapy prematurely if patients are not informed in advance about how to manage the effect. The same is true for other adverse effects such as somnolence and orthostatic hypotension. Educating patients and family members about potential treatment-emergent side effects and the importance of seeking assistance can mitigate premature abandonment of the therapy and prevent the side effect from becoming more severe.
Patients and families should be counseled about the drug's expected time to onset and response. Levodopa symptomatic benefit will be noted almost immediately (within a few doses or days). Dopamine agonists require initiation at a low (subtherapeutic) dose with gradual titration to a maintenance dose. This is done to minimize side effects. Thus, onset of a noticeable improvement usually takes more than 2 weeks. The onset of noticeable improvement with rasagiline may take several weeks, and the full effect may not be seen for up to 8 to 12 weeks.
Lack of awareness regarding a realistic onset of effect can lead to medication abandonment (because of the belief that the drug is ineffective) and polypharmacy (if other agents are prescribed to treat symptoms that have not yet responded to the initial agent).
Patients and families should be counseled about the risks of self-discontinuing a drug for PD. A worsening of motor symptoms would occur, and in some cases, discontinuation effects such as agitation, anxiety, diaphoresis, dysphoria, insomnia, or neuroleptic malignant syndrome may occur.
Parkinson's disease is a lifelong neurologic disorder. Patients will be on pharmacotherapy for the rest of their lives and will have many encounters with professionals in healthcare. Early-stage, mildly impairing PD will progress over time to advanced stages, with severe motor impairment and nonmotor deficits. For patients with early-stage PD and their families, dealing with the diagnosis, learning about PD and its prognosis, and accepting the need for lifelong therapy can be overwhelming. Clinicians, pharmacists, and allied healthcare personnel can help patients and families dealing with PD by ensuring that they receive adequate medication information at the time a new prescription is written and again when it is dispensed. Patients should be assessed for side effects, and the need for ongoing monitoring of medication efficacy and potential side effects should be discussed with the family.
Summary
Patients with early-stage PD will have many encounters with healthcare professionals during their lifetime. A better understanding of the motor and nonmotor symptoms of PD, risks and benefits of PD medications (Table), and drug-related complications will allow clinicians, pharmacists, and allied health professionals to better educate and manage patients. Thoughtful consideration about the initiation of pharmacotherapy for early-stage PD and information on realistic expectations of efficacy and side effects can help prevent therapy abandonment and improve clinician-patient management of PD.
Supported by an independent educational grant from Teva Neuroscience.
The management of Parkinson's disease (PD) is complex and involves nonpharmacologic and pharmacologic interventions for motor and nonmotor symptoms (see accompanying article by Dr. Simuni). The aim of this article is to provide a greater understanding of PD, treatment risks and benefits, and new developments in treatment approach that will allow clinicians, pharmacists, and allied healthcare personnel to better educate and care for patients with PD.
As PD progresses from early to advanced stages, medication adjustments and increased numbers of medications should be expected. This article will focus on pharmacotherapy interventions for early-stage PD with an emphasis on safety and drug interactions. A discussion about early interventions in PD, outcomes, and healthcare costs is available elsewhere.[1] Discussions regarding advanced stage PD, management of motor complications, and pharmacotherapies for nonmotor symptoms of PD are beyond the scope of this article and are also available elsewhere.[2]
The Patient With Early-Stage PD
An individual with early-stage PD who has been recently diagnosed may present with motor symptoms and absence of functional impairment or mild functional impairment (eg, clumsiness of the hands, mild deterioration in performance of sports activities, a bothersome tremor, worsening of handwriting). An untreated patient with early-stage PD will have a Unified Parkinson's Disease Rating Scale (UPDRS) score of 20 to 30.
The current pharmacologic management paradigm for early-stage PD consists of initiating 1 drug (ie, monotherapy) to provide symptomatic benefit. Drug therapy is typically initiated to address functional impairment. However, with the publication of the Attenuation of Disease progression with Azilect Given Once-daily (ADAGIO) study data, initiation of rasagiline in recently diagnosed patients with early PD presenting without functional impairment is a plausible approach.
In early-stage PD, monoamine oxidase type B (MAO-B) inhibitors, dopamine agonists, and levodopa (with a decarboxylase inhibitor such as carbidopa) all provide a sufficient magnitude of therapeutic effect. In addition to providing relief of tremor, rigidity, and/or slowness of movement, pharmacotherapy can also improve nonmotor symptoms such as fatigue in early PD and can improve experiences of daily living. If other symptoms such as constipation, depression, sexual dysfunction, and sleep disorders are present, adjunctive therapies that specifically target the symptom should also be considered.
Pharmacotherapy for Early-Stage PD: Safety, Side Effects, Drug Interactions
Drug safety and treatment-emergent side effects play a major role in guiding the selection and adjustment of pharmacotherapy in PD. Healthcare professionals involved in the pharmacotherapy management and distribution spectrum of PD should be concerned about the overall safety of the medications in this population, the safety of polypharmacy regimens and their necessity (or lack thereof), drug interactions, and education of the patient and family about benefits and risks of the medication regimen. Pharmacists, in particular, are traditionally more focused on drug safety and interactions as well as on providing instructions on proper use of medications.
Levodopa
Levodopa provides a robust magnitude of symptom relief effects. In patients with early PD, common side effects of levodopa include nausea and somnolence. Of note, hallucinations and psychosis are more common in patients with advanced stage PD. There is concern about the gradual emergence of motor complications (such as dyskinesias and fluctuations) associated with dose escalation and treatment duration. Motor complications can arise quickly (within a few months) or slowly (after a year or more). Although there are risk factors (eg, levodopa dose and treatment duration, younger age), no method has been found to predict which patients will experience motor complications.
The development of levodopa-associated motor complications has a significant impact on clinicians, patients, and healthcare resources. Motor complications can be a challenge for clinicians to manage, can impair patient health-related quality of life, and can increase direct health costs. Independent researchers and pharmaceutical manufacturers have devoted time and resources toward understanding the pathophysiology of motor complications and developing interventions that have specific efficacy for motor complications (eg, apomorphine, entacapone, rasagiline, selegiline oral disintegrating tablets, and deep brain stimulation). Eventually all patients with PD will be prescribed levodopa; however, in patients with early PD, other medications are available to provide adequate symptom relief without the risk for motor complications.
Pramipexole, ropinirole, and rasagiline are also indicated as monotherapy for PD. Clinicians and patients should engage in discussions about the relative risks and benefits of levodopa therapy, and patients should be allowed to make informed decisions.
Dopamine Agonists
The dopamine agonists (pramipexole, ropinirole) provide sufficient symptomatic effects for patients with early-stage PD and are less likely to cause motor complications. Side effects that are encountered by patients with early PD include nausea, somnolence, edema of the extremities, orthostatic hypotension, and impulse control disorders (ICDs). Of note, hallucinations may occur in patients with early PD, but are more common in advanced stage PD or patients with cognitive impairment.
Postmarketing recognition of the potential for dopamine agonist-induced ICDs has attracted much concern among clinicians who treat PD. ICDs can be a source of financial and familial strain for the patient. Common examples include excessive gambling, preoccupation with pornography, overindulgence in purchasing unnecessary items, excessive hobbyism, and preoccupation with Internet activities. The prospect of this potentially disruptive side effect should be communicated to the patient and family. Dopamine agonist-associated ICDs are not dose related and can also develop in patients receiving low daily doses for restless legs syndrome.
MAO-B Inhibitors
The MAO-B inhibitors (rasagiline, selegiline) provide modest symptomatic relief in patients with early PD. Of the available MAO-B inhibitors, rasagiline is the only one with labeling approved by the US Food and Drug Administration for monotherapy in PD. In addition, data from the ADAGIO study (a large, randomized, controlled trial) suggest that early initiation of rasagiline in patients with PD and the absence of functional impairment confer more benefit than delaying therapy.
Rasagiline is well tolerated in patients with early PD. Treatment-emergent side effects are nonspecific and include flulike weakness and asthenia. Overall, rasagiline is notable for its lack of dopaminergic side effects (eg, nausea, orthostasis, somnolence). Postmarketing data indicate that rasagiline can be safely administered without regard to meal content of tyramine (eg, in foods such as aged cheeses, red wine, sauerkraut). Based on clinical pharmacology studies, tyramine restriction is no longer required or advocated by the FDA when rasagiline is initiated. Likewise, sympathomimetic amines (eg, ephedrine, phenylephrine, phenylpropanolamine, pseudoephedrine) and local anesthesia with sympathomimetic vasoconstrictors can be administered concomitantly. Although the concurrent use of antidepressants (with serotonergic activity) is not contraindicated, benefits should be weighed against the potential for serotonin syndrome. The STACCATO study is underway to better define the potential occurrence of serotonin syndrome with rasagiline and antidepressants.[3]
Patient and Family Education
Patient and family education is critical for the safe and successful use of medications in patients with PD. The patient/family should be counseled about the adverse effects that are most likely to occur and when to report them to the prescriber. For example, ICDs such as Internet gambling could go undetected by family and unreported by patients and result in serious financial complications. Nausea, common with levodopa and dopamine agonists, is uncomfortable for patients, and in some circumstances, may cause discontinuation of therapy prematurely if patients are not informed in advance about how to manage the effect. The same is true for other adverse effects such as somnolence and orthostatic hypotension. Educating patients and family members about potential treatment-emergent side effects and the importance of seeking assistance can mitigate premature abandonment of the therapy and prevent the side effect from becoming more severe.
Patients and families should be counseled about the drug's expected time to onset and response. Levodopa symptomatic benefit will be noted almost immediately (within a few doses or days). Dopamine agonists require initiation at a low (subtherapeutic) dose with gradual titration to a maintenance dose. This is done to minimize side effects. Thus, onset of a noticeable improvement usually takes more than 2 weeks. The onset of noticeable improvement with rasagiline may take several weeks, and the full effect may not be seen for up to 8 to 12 weeks.
Lack of awareness regarding a realistic onset of effect can lead to medication abandonment (because of the belief that the drug is ineffective) and polypharmacy (if other agents are prescribed to treat symptoms that have not yet responded to the initial agent).
Patients and families should be counseled about the risks of self-discontinuing a drug for PD. A worsening of motor symptoms would occur, and in some cases, discontinuation effects such as agitation, anxiety, diaphoresis, dysphoria, insomnia, or neuroleptic malignant syndrome may occur.
Parkinson's disease is a lifelong neurologic disorder. Patients will be on pharmacotherapy for the rest of their lives and will have many encounters with professionals in healthcare. Early-stage, mildly impairing PD will progress over time to advanced stages, with severe motor impairment and nonmotor deficits. For patients with early-stage PD and their families, dealing with the diagnosis, learning about PD and its prognosis, and accepting the need for lifelong therapy can be overwhelming. Clinicians, pharmacists, and allied healthcare personnel can help patients and families dealing with PD by ensuring that they receive adequate medication information at the time a new prescription is written and again when it is dispensed. Patients should be assessed for side effects, and the need for ongoing monitoring of medication efficacy and potential side effects should be discussed with the family.
Summary
Patients with early-stage PD will have many encounters with healthcare professionals during their lifetime. A better understanding of the motor and nonmotor symptoms of PD, risks and benefits of PD medications (Table), and drug-related complications will allow clinicians, pharmacists, and allied health professionals to better educate and manage patients. Thoughtful consideration about the initiation of pharmacotherapy for early-stage PD and information on realistic expectations of efficacy and side effects can help prevent therapy abandonment and improve clinician-patient management of PD.
Supported by an independent educational grant from Teva Neuroscience.
Wednesday, June 2, 2010
Pramipexole for the treatment of depressive symptoms in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled trial.
Bxarone P, Poewe W, Albrecht S, Debieuvre C, Massey D, Rascol O, Tolosa E, Weintraub D.
Department of Neurological Sciences, University of Naples Federico II and IDC Hermitage Capodimonte, Naples, Italy. barone@unina.it
Abstract
BACKGROUND: Depression is common in patients with Parkinson's disease, but evidence on the efficacy of antidepressants in this population is lacking. Because depression in patients with Parkinson's disease might be related to dopaminergic dysfunction, we aimed to assess the efficacy of the dopamine agonist pramipexole for treatment of depressive symptoms in patients with Parkinson's disease. METHODS: We did a 12-week randomised, double-blind, placebo-controlled (1:1 ratio) trial of pramipexole (0.125-1.0 mg three times per day) compared with placebo in patients with mild-to-moderate Parkinson's disease. Patients from 76 centres in 12 European countries and South Africa were included if they were on stable antiparkinsonian therapy without motor fluctuations and had depressive symptoms (15-item geriatric depression scale score > or =5 and unified Parkinson's disease rating scale [UPDRS] part 1 depression item score > or =2). Patients were randomly assigned by centre in blocks of four by use of a randomisation number generating system. Clinical monitors, the principal investigator, and patients were masked to treatment allocation. The primary endpoint was change in Beck depression inventory (BDI) score and all treated patients who had at least one post-baseline efficacy assessment were included in the primary analysis. We also did a pre-specified path analysis with regression models to assess the relation between BDI and UPDRS part 3 (motor score) changes. This trial is registered with ClinicalTrials.gov, number NCT00297778, and EudraCT, number 2005-003788-22. FINDINGS: Between March, 2006, and February, 2008, we enrolled 323 patients. Of 296 patients randomly assigned to pramipexole or placebo, 287 were included in the primary analysis: 139 in the pramipexole group and 148 in the placebo group. BDI scores decreased by an adjusted mean 5.9 (SE 0.5) points in the pramipexole group and 4.0 (0.5) points in the placebo group (difference 1.9, 95% CI 0.5-3.4; p=0.01, ANCOVA). The UPDRS motor score decreased by an adjusted mean 4.4 (0.6) points in the pramipexole group and 2.2 (0.5) points in the placebo group (difference 2.2, 95% CI 0.7-3.7; p=0.003, ANCOVA). Path analysis showed the direct effect of pramipexole on depressive symptoms accounted for 80% of total treatment effect (p=0.04). Adverse events were reported in 105 of 144 patients in the pramipexole group and 101 of 152 in the placebo group. Adverse events in the pramipexole group were consistent with the known safety profile of the drug. INTERPRETATION: Pramipexole improved depressive symptoms in patients with Parkinson's disease, mainly through a direct antidepressant effect. This effect should be considered in the clinical management of patients with Parkinson's disease. Copyright 2010 Elsevier Ltd. All rights reserved.
Department of Neurological Sciences, University of Naples Federico II and IDC Hermitage Capodimonte, Naples, Italy. barone@unina.it
Abstract
BACKGROUND: Depression is common in patients with Parkinson's disease, but evidence on the efficacy of antidepressants in this population is lacking. Because depression in patients with Parkinson's disease might be related to dopaminergic dysfunction, we aimed to assess the efficacy of the dopamine agonist pramipexole for treatment of depressive symptoms in patients with Parkinson's disease. METHODS: We did a 12-week randomised, double-blind, placebo-controlled (1:1 ratio) trial of pramipexole (0.125-1.0 mg three times per day) compared with placebo in patients with mild-to-moderate Parkinson's disease. Patients from 76 centres in 12 European countries and South Africa were included if they were on stable antiparkinsonian therapy without motor fluctuations and had depressive symptoms (15-item geriatric depression scale score > or =5 and unified Parkinson's disease rating scale [UPDRS] part 1 depression item score > or =2). Patients were randomly assigned by centre in blocks of four by use of a randomisation number generating system. Clinical monitors, the principal investigator, and patients were masked to treatment allocation. The primary endpoint was change in Beck depression inventory (BDI) score and all treated patients who had at least one post-baseline efficacy assessment were included in the primary analysis. We also did a pre-specified path analysis with regression models to assess the relation between BDI and UPDRS part 3 (motor score) changes. This trial is registered with ClinicalTrials.gov, number NCT00297778, and EudraCT, number 2005-003788-22. FINDINGS: Between March, 2006, and February, 2008, we enrolled 323 patients. Of 296 patients randomly assigned to pramipexole or placebo, 287 were included in the primary analysis: 139 in the pramipexole group and 148 in the placebo group. BDI scores decreased by an adjusted mean 5.9 (SE 0.5) points in the pramipexole group and 4.0 (0.5) points in the placebo group (difference 1.9, 95% CI 0.5-3.4; p=0.01, ANCOVA). The UPDRS motor score decreased by an adjusted mean 4.4 (0.6) points in the pramipexole group and 2.2 (0.5) points in the placebo group (difference 2.2, 95% CI 0.7-3.7; p=0.003, ANCOVA). Path analysis showed the direct effect of pramipexole on depressive symptoms accounted for 80% of total treatment effect (p=0.04). Adverse events were reported in 105 of 144 patients in the pramipexole group and 101 of 152 in the placebo group. Adverse events in the pramipexole group were consistent with the known safety profile of the drug. INTERPRETATION: Pramipexole improved depressive symptoms in patients with Parkinson's disease, mainly through a direct antidepressant effect. This effect should be considered in the clinical management of patients with Parkinson's disease. Copyright 2010 Elsevier Ltd. All rights reserved.
Tuesday, May 4, 2010
Singapore scientists develop zebrafish model for studying Parkinson's Disease
Singapore scientists develop zebrafish model for studying Parkinson's Disease
Scientists at the Genome Institute of Singapore (GIS), a biomedical research institute of the Agency for Science, Technology and Research (A*STAR), have recently developed a zebrafish model for Parkinson's disease that can be used for understanding the mechanism underlying its development. The knowledge gained will be helpful for future screening of new drugs to treat Parkinson's disease (PD).
This study describes the first zebrafish model for LRRK2 mutation-related PD. It is able to overcome some limitations of other animal models of LRRK2 and demonstrates that zebrafish, a tropical freshwater fish that can often be found in aquariums, can be used to study the development of human diseases. Led by GIS Group Leader Dr Liu Jianjun, the finding was published in PLoS Genetics on April 22, 2010.
To explore the biological functions of LRRK2, the scientists studied this gene in zebrafish by blocking its normal function. This resulted in Parkinsonism-like phenotypes in zebrafish, including locomotive defects and loss of neurons, similar to those of PD patients. It was found from the study that the defects of the fish can be rescued by expressing the normal protein of LRRK2. Significantly, the administration of Levo-dopa (L-dopa), a compound that is widely used to treat PD, can also rescue the locomotive defects caused by the modification of the zebrafish LRRK2 protein.
Parkinson's disease (PD) is a degenerative disease of the brain that often impairs motor skills, speech and other functions. The discovery of several gene mutations in affected patients clearly demonstrated the involvement of genetic factors in the development of PD. LRRK2 was discovered from previous studies by the same team of researchers to be one of the most important genetic causes of PD in the Asian population.
"This work shows how the use of a simple model system in fish can help decipher the root causes of a serious human disorder like Parkinson's disease, " said Professor Edison Liu, Executive Director of the GIS.
Dr Lim Kah Leong, Associate Professor of the National Neuroscience Institute and Duke-NUS Graduate Medical School, added "This novel and elegant study has illuminated the role of an otherwise poorly understood but important domain of LRRK2 that is associated with an increased risk for Parkinson's disease amongst Asian populations. The use of zebrafish as a disease model is a clever approach. I am definitely pleased to note that our arsenal of experimental organisms for drug screening has expanded with this study."
The zebrafish model derived from this study serves as a vertebrate model suitable for large-scale drug screening and provides a good disease model for PD. Using a novel technology known as the Zinc-finger nucleases (ZFNs), further research is being carried out to generate additional mutations of zebrafish LRRK2 gene. Such mutated zebrafishes can be used for advancing investigation for the biological mechanism of PD and screening of new drugs for PD treatment.
More information: The research findings can be found in the April 22, 2010 print issue of PLoS GENETICS under the title "Deletion of the WD40 Domain of LRRK2 in Zebrafish Causes Parkinsonism-Like Loss of Neurons and Locomotive Defect".
Provided by Agency for Science, Technology and Research (A*STAR)
Scientists at the Genome Institute of Singapore (GIS), a biomedical research institute of the Agency for Science, Technology and Research (A*STAR), have recently developed a zebrafish model for Parkinson's disease that can be used for understanding the mechanism underlying its development. The knowledge gained will be helpful for future screening of new drugs to treat Parkinson's disease (PD).
This study describes the first zebrafish model for LRRK2 mutation-related PD. It is able to overcome some limitations of other animal models of LRRK2 and demonstrates that zebrafish, a tropical freshwater fish that can often be found in aquariums, can be used to study the development of human diseases. Led by GIS Group Leader Dr Liu Jianjun, the finding was published in PLoS Genetics on April 22, 2010.
To explore the biological functions of LRRK2, the scientists studied this gene in zebrafish by blocking its normal function. This resulted in Parkinsonism-like phenotypes in zebrafish, including locomotive defects and loss of neurons, similar to those of PD patients. It was found from the study that the defects of the fish can be rescued by expressing the normal protein of LRRK2. Significantly, the administration of Levo-dopa (L-dopa), a compound that is widely used to treat PD, can also rescue the locomotive defects caused by the modification of the zebrafish LRRK2 protein.
Parkinson's disease (PD) is a degenerative disease of the brain that often impairs motor skills, speech and other functions. The discovery of several gene mutations in affected patients clearly demonstrated the involvement of genetic factors in the development of PD. LRRK2 was discovered from previous studies by the same team of researchers to be one of the most important genetic causes of PD in the Asian population.
"This work shows how the use of a simple model system in fish can help decipher the root causes of a serious human disorder like Parkinson's disease, " said Professor Edison Liu, Executive Director of the GIS.
Dr Lim Kah Leong, Associate Professor of the National Neuroscience Institute and Duke-NUS Graduate Medical School, added "This novel and elegant study has illuminated the role of an otherwise poorly understood but important domain of LRRK2 that is associated with an increased risk for Parkinson's disease amongst Asian populations. The use of zebrafish as a disease model is a clever approach. I am definitely pleased to note that our arsenal of experimental organisms for drug screening has expanded with this study."
The zebrafish model derived from this study serves as a vertebrate model suitable for large-scale drug screening and provides a good disease model for PD. Using a novel technology known as the Zinc-finger nucleases (ZFNs), further research is being carried out to generate additional mutations of zebrafish LRRK2 gene. Such mutated zebrafishes can be used for advancing investigation for the biological mechanism of PD and screening of new drugs for PD treatment.
More information: The research findings can be found in the April 22, 2010 print issue of PLoS GENETICS under the title "Deletion of the WD40 Domain of LRRK2 in Zebrafish Causes Parkinsonism-Like Loss of Neurons and Locomotive Defect".
Provided by Agency for Science, Technology and Research (A*STAR)
Saturday, March 6, 2010
Local Resident Graduates from Parkinson's Research Advocacy Training Program
Local Resident Graduates from Parkinson's Research Advocacy Training Program
Aim Vernon
Local Resident Graduates from Parkinson's Research Advocacy Training Program
Recently, more than forty people living with Parkinson's disease (PD) from across the US, including one Highland Lakes resident, participated in the Parkinson's Disease Foundation's (PDF) Second Clinical Research Learning Institute in nearby Florham Park. The Learning Institute educated its participants about the ways that people living with Parkinson's can contribute to new treatments and a cure for the disease.
Local advocate Geraldine Mulligan was among the diverse group of business leaders, scientists and educators that traveled from 24 states to participate. Ms. Mulligan is a retired businesswoman who held positions with both small local businesses and a Fortune 500 company in New Jersey. Since she was diagnosed over 10 years ago with Parkinson’s, she has been very involved with her community and church. She recently decided to take a more active role within Parkinson’s advocacy.
During the training, Ms. Mulligan attended three days of courses led by national experts, who covered topics such as the basics of clinical research and discussed the potential new Parkinson’s therapies that are currently being studied by scientists. Back home, she is ready to work on a local level to impact the development of new therapies and to raise awareness among people living with Parkinson’s about the role that they can play.
Ms. Mulligan, spoke of her experiences, "I learned so much valuable information at the Learning Institute about how people with Parkinson’s can impact the development of new treatments for our disease. I believe that everyone living with the disease deserves to have access to this information, so I hope to work locally spread the word about the importance of clinical studies in finding new therapies. As part of this work, I am trying to establish an active support group in our area, which among other tasks, would serve to raise awareness about clinical studies."
Executive Director Robin Elliott, commented on the training, "The Parkinson's Disease Foundation believes that inclusion of the perspective and experiences of people with Parkinson's has the potential to benefit the clinical research process and therapies development. We are committed to providing the tools and resources necessary to make this happen – in the hope that the Clinical Research Learning Institute provides the foundation for these motivated consumers to become engaged and involved in a process that directly impacts their current quality of life and strives to find a cure for this debilitating disease."
Aim Vernon
Local Resident Graduates from Parkinson's Research Advocacy Training Program
Recently, more than forty people living with Parkinson's disease (PD) from across the US, including one Highland Lakes resident, participated in the Parkinson's Disease Foundation's (PDF) Second Clinical Research Learning Institute in nearby Florham Park. The Learning Institute educated its participants about the ways that people living with Parkinson's can contribute to new treatments and a cure for the disease.
Local advocate Geraldine Mulligan was among the diverse group of business leaders, scientists and educators that traveled from 24 states to participate. Ms. Mulligan is a retired businesswoman who held positions with both small local businesses and a Fortune 500 company in New Jersey. Since she was diagnosed over 10 years ago with Parkinson’s, she has been very involved with her community and church. She recently decided to take a more active role within Parkinson’s advocacy.
During the training, Ms. Mulligan attended three days of courses led by national experts, who covered topics such as the basics of clinical research and discussed the potential new Parkinson’s therapies that are currently being studied by scientists. Back home, she is ready to work on a local level to impact the development of new therapies and to raise awareness among people living with Parkinson’s about the role that they can play.
Ms. Mulligan, spoke of her experiences, "I learned so much valuable information at the Learning Institute about how people with Parkinson’s can impact the development of new treatments for our disease. I believe that everyone living with the disease deserves to have access to this information, so I hope to work locally spread the word about the importance of clinical studies in finding new therapies. As part of this work, I am trying to establish an active support group in our area, which among other tasks, would serve to raise awareness about clinical studies."
Executive Director Robin Elliott, commented on the training, "The Parkinson's Disease Foundation believes that inclusion of the perspective and experiences of people with Parkinson's has the potential to benefit the clinical research process and therapies development. We are committed to providing the tools and resources necessary to make this happen – in the hope that the Clinical Research Learning Institute provides the foundation for these motivated consumers to become engaged and involved in a process that directly impacts their current quality of life and strives to find a cure for this debilitating disease."
Advil May Reduce Parkinson’s Risk
By Monika L. S. Robbins, CONTRIBUTING WRITER
The anti-inflammatory drug ibuprofen may act as a neuroprotective agent against the risk of Parkinson’s disease, according to researchers at the Harvard School of Public Health.
In the observational study, participants who regularly used ibuprofen were 40 percent less likely to develop Parkinson’s disease over a six-year period, according to lead researcher Xiang Gao, an instructor in medicine at HSPH.
These findings confirmed the results of a 2005 study that found that users of non-steroidal, anti-inflammatory drugs—including ibuprofen—displayed a lower risk of developing Parkinson’s disease.
The current study focused on ibuprofen, which can be purchased over the counter in the form of popular brands such as Advil.
Over six years, 130,000 subjects self-reported their health statuses and specifically noted their use of ibuprofen and whether they had been diagnosed with Parkinson’s disease.
The study found that 15 to 20 percent of participants regularly used ibuprofen, and 291 individuals were diagnosed with the disease within the six-year timeframe.
Despite the suggestions of a correlation between ibuprofen use and risk of Parkinson’s disease, the Harvard researchers said that the study’s findings cannot be used to reach any conclusions because the research was purely observational and did not examine causality.
The next step is to “take advantage” of the study’s findings by further exploring the relationship between ibuprofen use and risk of Parkinson’s disease, said Michael A. Schwarzschild, an associate professor of neurology at Harvard Medical School and one of the study’s authors.
Schwarzschild said that it is not surprising that anti-inflammatory medication like ibuprofen may help reduce the risk of the disease, which involves inflammation of the brain. But scientists have yet to determine exactly why ibuprofen may be more effective as a neuroprotective agent than other anti-inflammatory drugs, Schwarzschild explained.
Parkinson’s disease is a chronic neurological disorder that progressively slows down movement. Dubbed “the shaking palsy” by its discoverer James Parkinson, the disease is characterized by a “rest tremor,” a steady shaking that typically begins in one hand while a patient is at rest, according to Schwarzschild.
The disease is also associated with dementia, depression, and other disorders. According to the National Parkinson Foundation, 60,000 new cases of Parkinson’s disease are diagnosed each year.
The study—which will be presented in April at the American Academy of Neurology meeting in Toronto—also involved researchers Honglei Chen and Alberto Ascherio, a professor of epidemiology and nutrition at HMS.
The anti-inflammatory drug ibuprofen may act as a neuroprotective agent against the risk of Parkinson’s disease, according to researchers at the Harvard School of Public Health.
In the observational study, participants who regularly used ibuprofen were 40 percent less likely to develop Parkinson’s disease over a six-year period, according to lead researcher Xiang Gao, an instructor in medicine at HSPH.
These findings confirmed the results of a 2005 study that found that users of non-steroidal, anti-inflammatory drugs—including ibuprofen—displayed a lower risk of developing Parkinson’s disease.
The current study focused on ibuprofen, which can be purchased over the counter in the form of popular brands such as Advil.
Over six years, 130,000 subjects self-reported their health statuses and specifically noted their use of ibuprofen and whether they had been diagnosed with Parkinson’s disease.
The study found that 15 to 20 percent of participants regularly used ibuprofen, and 291 individuals were diagnosed with the disease within the six-year timeframe.
Despite the suggestions of a correlation between ibuprofen use and risk of Parkinson’s disease, the Harvard researchers said that the study’s findings cannot be used to reach any conclusions because the research was purely observational and did not examine causality.
The next step is to “take advantage” of the study’s findings by further exploring the relationship between ibuprofen use and risk of Parkinson’s disease, said Michael A. Schwarzschild, an associate professor of neurology at Harvard Medical School and one of the study’s authors.
Schwarzschild said that it is not surprising that anti-inflammatory medication like ibuprofen may help reduce the risk of the disease, which involves inflammation of the brain. But scientists have yet to determine exactly why ibuprofen may be more effective as a neuroprotective agent than other anti-inflammatory drugs, Schwarzschild explained.
Parkinson’s disease is a chronic neurological disorder that progressively slows down movement. Dubbed “the shaking palsy” by its discoverer James Parkinson, the disease is characterized by a “rest tremor,” a steady shaking that typically begins in one hand while a patient is at rest, according to Schwarzschild.
The disease is also associated with dementia, depression, and other disorders. According to the National Parkinson Foundation, 60,000 new cases of Parkinson’s disease are diagnosed each year.
The study—which will be presented in April at the American Academy of Neurology meeting in Toronto—also involved researchers Honglei Chen and Alberto Ascherio, a professor of epidemiology and nutrition at HMS.
Sunday, February 21, 2010
Placebo treatments stronger than doctors thought
By MARIA CHENG AP Medical Writer © 2010 The Associated Press
LONDON — When it comes to the placebo effect, it really may be mind over matter, a new analysis suggests.
In a review of recent research, international experts say there is increasing evidence that fake treatments, or placebos, have an actual biological effect in the body.
The doctor-patient relationship, plus the expectation of recovery, may sometimes be enough to change a patient's brain, body and behavior, experts write. The review of previous research on placebos was published online Friday in Lancet, the British medical journal.
"It's not that placebos or inert substances help," said Linda Blair, a Bath-based psychologist and spokeswoman for the British Psychological Society. Blair was not linked to the research. "It's that people's belief in inert substances help."
While doctors have long recognized that placebos can help patients feel better, they weren't sure if the treatments sparked any physical changes.
In the Lancet review, researchers cite studies where patients with Parkinson's disease were given dummy pills. That led their brains to release dopamine, a feel-good chemical, and also resulted in other changes in brain activity.
"When you think you're going to get a drug that helps, your brain reacts as if it's getting relief," said Walter Brown, a clinical professor of psychiatry at Brown and Tufts University. "But we don't know how that thought that you're going to get better actually translates into something happening in the brain."
With growing proof that placebos work, some doctors are trying to figure out how to capitalize on their effects, without being unethical.
Blair said that to be completely honest with patients — to tell them they were receiving a fake treatment — would sabotage their belief in the drug, and thus, undermine any potential benefit.
But Brown didn't agree. For certain patients, like those with mild depression or anxiety, he said placebos were likely to work just as well as established therapies.
He said that even if doctors acknowledge they are giving such patients a placebo medication, but say it could be beneficial, "it might just actually work."
LONDON — When it comes to the placebo effect, it really may be mind over matter, a new analysis suggests.
In a review of recent research, international experts say there is increasing evidence that fake treatments, or placebos, have an actual biological effect in the body.
The doctor-patient relationship, plus the expectation of recovery, may sometimes be enough to change a patient's brain, body and behavior, experts write. The review of previous research on placebos was published online Friday in Lancet, the British medical journal.
"It's not that placebos or inert substances help," said Linda Blair, a Bath-based psychologist and spokeswoman for the British Psychological Society. Blair was not linked to the research. "It's that people's belief in inert substances help."
While doctors have long recognized that placebos can help patients feel better, they weren't sure if the treatments sparked any physical changes.
In the Lancet review, researchers cite studies where patients with Parkinson's disease were given dummy pills. That led their brains to release dopamine, a feel-good chemical, and also resulted in other changes in brain activity.
"When you think you're going to get a drug that helps, your brain reacts as if it's getting relief," said Walter Brown, a clinical professor of psychiatry at Brown and Tufts University. "But we don't know how that thought that you're going to get better actually translates into something happening in the brain."
With growing proof that placebos work, some doctors are trying to figure out how to capitalize on their effects, without being unethical.
Blair said that to be completely honest with patients — to tell them they were receiving a fake treatment — would sabotage their belief in the drug, and thus, undermine any potential benefit.
But Brown didn't agree. For certain patients, like those with mild depression or anxiety, he said placebos were likely to work just as well as established therapies.
He said that even if doctors acknowledge they are giving such patients a placebo medication, but say it could be beneficial, "it might just actually work."
Wednesday, January 20, 2010
A Yeast Contribution For The Treatment Of Parkinson’s Disease
Scientists have just identified several molecules capable of reversing the brain abnormalities of Parkinson’s disease (PD), while also uncovering new clues for its origin in a study just published in the journal Disease Models and Mechanisms (1). PD is characterised by abnormal deposits of a brain protein called alpha-synuclein throughout the damaged brain regions, but exactly what they do there is not clear. The fact that their numbers and spreading are associated disease progression has made them, however, a major point of interest in PD research. The work now published suggests that these deposits are actually a normal physiological process to purge unwanted proteins but, when “overloaded”, they can also cause of the cellular abnormalities seen in PD neurons and, ultimately, neural death. This would explain why the disease tends to appear later in life when the whole metabolism (including this mechanism) becomes less efficient, and also why neurons are particularly susceptible as they are one of the few cells of the body that are not replaced when old and less capable. The study uses a yeast model of PD showing once again the power of simple organism models in the understanding of extremely complex human diseases.
PD is neurodegenerative disease characterised by increasing motor problems - tremors, rigidity and balance and coordination problems - that can leave the patient incapable of perform the simplest of everyday task. Many patients also suffer from non-motor symptoms, including dementia. There is also widespread death of dopamine-producing (dopaminergic) neurons in a part of the brain called the substantia nigra. Since dopamine acts as messenger between this region (the control centre) and other neurons around the body to ensure proper regulation of the body’s movement, these deaths are believed to cause PD motor disability.
Although the symptoms can be treated with dopamine replacement therapies, as the disease progresses, they stop working and, more importantly, PD is, ultimately, incurable. With the spread of the disease throughout an increasing aging human population bringing dramatic financial and social costs (who will take care of these millions of patients?), new treatments and/or a cure are now being exhaustively researched.
A major focus of the research has been a brain protein of unknown function called alpha-synuclein. In fact, deposits of abnormally folded alpha-synuclein (a certain folding is associated to the proper functioning of each protein) are found in inclusions dispersed all over the damaged brain areas of PD patients. The role of these inclusions in disease is not known with hypotheses ranging from having no importance, to contribute to neural death or even serve to avoid death by rendering harmless toxic misfolded proteins. What is known, however, is that these alpha-synuclein inclusions are excellent markers of disease progression – they accompany the brain degeneration.
In 2003 Tiago Outeiro - a Portuguese scientist and one of the first authors of the new study - and Susan Lindquist – the team leader in both studies – created a yeast model of PD by inserting the alpha-synuclein gene in yeast, an organism that normally does not have the protein. Remarkably, this created in yeast some of the cellular abnormalities seen in PD affected neurons. And as alpha-synuclein quantities increased, also the numbers of inclusions containing the protein, in such a way that led the researchers to suggest that these were, in fact, a physiological process for getting rid of unwanted proteins. And that maybe PD appeared when the capacity of the system was exceed. This hypothesis was supported by the fact that multiplications of the normal alpha-synuclein gene (leading to protein overproduction) were known to cause some forms of human PD, and also by the disease tendency for a late onset, probably due to an aging and less metabolically capable body.
To test this possibility in the study now published, Linhui Julie Su, Pavan K. Auluck, Tiago Fleming Outeiro and Susan Lindquist, working at the Whitehead Institute for Biomedical Research, Cambridge USA, created yet another yeast PD model this time with even higher levels of alpha-synuclein (High-syn) by inserting extra copies of the gene in the yeast genome. This PD model was then compared with yeast producing none or intermediate levels of alpha-synuclein (Int-syn) (this last organism was the one used in the 2003 study)
Remarkably, the new High-syn yeast suffered from several more of the cellular abnormalities characteristic of PD than the Int-syn yeast. The new abnormalities included problems with mitochondria (the energy producing factories of the cell) as well as accumulation of toxic free radicals, in addition to the abnormalities in lipid transport mechanisms already detected in Int-syn yeast. Problems in mitochondria and accumulation of free radicals are particularly interesting as, although seen in many PD patients, until now they had been impossible to link to alpha-synuclein.
Next, to exploit the fact that the new (High-syn ) yeast PD model shared so many cellular features with its human counterpart the researchers tried to look for possible therapies. For that Su, Auluck and Outeiro tested 115,000 bioactive (so known to affect live cells) compounds and found several able to correct one or more of the cellular abnormalities induced by the high levels of alpha-synuclein. Not only that, but these molecules were also effective treating worm and mammals (rat) models of PD. Even more remarkably, they were capable of rescuing human dopaminergic neurons in a third PD model raising the possibility that they could be used to treat human PD.
Interestingly several of these new potentially therapeutic molecules looked very similar, what led Su and colleagues to test them against each other to find that, in fact, they acted on the same targets across the different species tested. This was particularly important because it shows that the biological mechanisms affected by the over-accumulation of alpha-synuclein are conserved throughout millions of years of evolution - from yeast to humans – further supporting the hypothesis that PD results from a dysfunction of basic cellular mechanisms.
In conclusion Su, Auluck and Outeiro´s work supports the idea that accumulation of alpha-synuclein in vesicles inside brain cells, so typical of PD, is a normal physiological mechanism, most probably to get rid of abnormal proteins. Overload of this mechanism seems enough to cause PD-like symptoms (after all in these yeast models the protein is perfectly normal). Neurons are particularly susceptible not only because they are not renewed throughout the organism’s life, but also because they have higher than normal requirements for both mitochondria and lipid metabolism due to their highly energetic functions.
The new study’s major breakthrough, however, is the identification of several new compounds apparently capable of reversing the cellular abnormalities associated with PD and, as such, with potential to be used in treatments against the brain degeneration of PD.
In fact, at the moment the disease is believed to already affect a striking 3% of the population above 65 years old (more than 1 million in the US, 1,2 millions in Europe) and in a world where life expectancy is steadily increasing, pushing PD numbers (by the age of 80 more than 2 out of 100 people will have signs of the condition), any clues into the disease mechanisms and possible treatments are crucial.
Still, much more work is needed before therapies can be developed “The next step - says Tiago Outeiro - is to confirm these results in other PD models, even more similar to the human disease, to understand better the mechanisms and identify the molecules’ targets so they can, if proven secure, be eventually tested in humans”
For more information go to www.parkinsonresearchfoundation.org
PD is neurodegenerative disease characterised by increasing motor problems - tremors, rigidity and balance and coordination problems - that can leave the patient incapable of perform the simplest of everyday task. Many patients also suffer from non-motor symptoms, including dementia. There is also widespread death of dopamine-producing (dopaminergic) neurons in a part of the brain called the substantia nigra. Since dopamine acts as messenger between this region (the control centre) and other neurons around the body to ensure proper regulation of the body’s movement, these deaths are believed to cause PD motor disability.
Although the symptoms can be treated with dopamine replacement therapies, as the disease progresses, they stop working and, more importantly, PD is, ultimately, incurable. With the spread of the disease throughout an increasing aging human population bringing dramatic financial and social costs (who will take care of these millions of patients?), new treatments and/or a cure are now being exhaustively researched.
A major focus of the research has been a brain protein of unknown function called alpha-synuclein. In fact, deposits of abnormally folded alpha-synuclein (a certain folding is associated to the proper functioning of each protein) are found in inclusions dispersed all over the damaged brain areas of PD patients. The role of these inclusions in disease is not known with hypotheses ranging from having no importance, to contribute to neural death or even serve to avoid death by rendering harmless toxic misfolded proteins. What is known, however, is that these alpha-synuclein inclusions are excellent markers of disease progression – they accompany the brain degeneration.
In 2003 Tiago Outeiro - a Portuguese scientist and one of the first authors of the new study - and Susan Lindquist – the team leader in both studies – created a yeast model of PD by inserting the alpha-synuclein gene in yeast, an organism that normally does not have the protein. Remarkably, this created in yeast some of the cellular abnormalities seen in PD affected neurons. And as alpha-synuclein quantities increased, also the numbers of inclusions containing the protein, in such a way that led the researchers to suggest that these were, in fact, a physiological process for getting rid of unwanted proteins. And that maybe PD appeared when the capacity of the system was exceed. This hypothesis was supported by the fact that multiplications of the normal alpha-synuclein gene (leading to protein overproduction) were known to cause some forms of human PD, and also by the disease tendency for a late onset, probably due to an aging and less metabolically capable body.
To test this possibility in the study now published, Linhui Julie Su, Pavan K. Auluck, Tiago Fleming Outeiro and Susan Lindquist, working at the Whitehead Institute for Biomedical Research, Cambridge USA, created yet another yeast PD model this time with even higher levels of alpha-synuclein (High-syn) by inserting extra copies of the gene in the yeast genome. This PD model was then compared with yeast producing none or intermediate levels of alpha-synuclein (Int-syn) (this last organism was the one used in the 2003 study)
Remarkably, the new High-syn yeast suffered from several more of the cellular abnormalities characteristic of PD than the Int-syn yeast. The new abnormalities included problems with mitochondria (the energy producing factories of the cell) as well as accumulation of toxic free radicals, in addition to the abnormalities in lipid transport mechanisms already detected in Int-syn yeast. Problems in mitochondria and accumulation of free radicals are particularly interesting as, although seen in many PD patients, until now they had been impossible to link to alpha-synuclein.
Next, to exploit the fact that the new (High-syn ) yeast PD model shared so many cellular features with its human counterpart the researchers tried to look for possible therapies. For that Su, Auluck and Outeiro tested 115,000 bioactive (so known to affect live cells) compounds and found several able to correct one or more of the cellular abnormalities induced by the high levels of alpha-synuclein. Not only that, but these molecules were also effective treating worm and mammals (rat) models of PD. Even more remarkably, they were capable of rescuing human dopaminergic neurons in a third PD model raising the possibility that they could be used to treat human PD.
Interestingly several of these new potentially therapeutic molecules looked very similar, what led Su and colleagues to test them against each other to find that, in fact, they acted on the same targets across the different species tested. This was particularly important because it shows that the biological mechanisms affected by the over-accumulation of alpha-synuclein are conserved throughout millions of years of evolution - from yeast to humans – further supporting the hypothesis that PD results from a dysfunction of basic cellular mechanisms.
In conclusion Su, Auluck and Outeiro´s work supports the idea that accumulation of alpha-synuclein in vesicles inside brain cells, so typical of PD, is a normal physiological mechanism, most probably to get rid of abnormal proteins. Overload of this mechanism seems enough to cause PD-like symptoms (after all in these yeast models the protein is perfectly normal). Neurons are particularly susceptible not only because they are not renewed throughout the organism’s life, but also because they have higher than normal requirements for both mitochondria and lipid metabolism due to their highly energetic functions.
The new study’s major breakthrough, however, is the identification of several new compounds apparently capable of reversing the cellular abnormalities associated with PD and, as such, with potential to be used in treatments against the brain degeneration of PD.
In fact, at the moment the disease is believed to already affect a striking 3% of the population above 65 years old (more than 1 million in the US, 1,2 millions in Europe) and in a world where life expectancy is steadily increasing, pushing PD numbers (by the age of 80 more than 2 out of 100 people will have signs of the condition), any clues into the disease mechanisms and possible treatments are crucial.
Still, much more work is needed before therapies can be developed “The next step - says Tiago Outeiro - is to confirm these results in other PD models, even more similar to the human disease, to understand better the mechanisms and identify the molecules’ targets so they can, if proven secure, be eventually tested in humans”
For more information go to www.parkinsonresearchfoundation.org
Monday, January 11, 2010
Acid associated with gout 'could help Parkinson's sufferers'
By Kate Devlin,
Parkinson’s disease progresses more slowly in patients with naturally high levels of the acid which triggers gout, suggesting a possible new treatment for the disease.
Patients with high levels of uric acid were a third less likely to need treatment over the course of two years than those with low levels, the results of a new study show.
Researchers are now testing whether increasing Parkinson’s patients’ uric acid levels safely can help their condition.
An antioxidant, the acid is created naturally as we digest food.
But too much uric acid, or urate, can cause bouts of gout, an extremely painful joint condition, and kidney stones.
Diets rich in liver, seafood and dried beans have been linked to high uric acid levels but researchers warn that because of the side effects patients should not try to increase their urate levels themselves.
A smaller study published last year also suggested that high uric acid levels could slow the progression of Parkinson’s Disease.
Dr Alberto Ascherio, from the Harvard School of Public Health, who led the study, said: “Only now we can be reasonably sure that the slower rate of progression in patients with higher concentrations of urate is real and not a chance occurrence."
However, the researchers stress that they do not yet know if it is the acid itself which carries the protective benefit or some other process of the body which produces uric acid as a by-product.
The latest research looked at 800 sufferers of the condition.
The link between high uric acid levels and a slower development of the disease was less clear in women then men, the study found, however this may be because women tend to have higher natural levels of the acid.
The researchers are now conducting a trial to give 90 patients a drug, inosine, which can elevate uric acid levels, to test whether they can be safely raised and if this slows the speed of the disease.
"Because elevated urate levels have known health risks, including gout and kidney stones urate elevation should only be attempted in the context of a closely monitored clinical trial in which potential benefits and risks are carefully balanced," Dr Schwarzschild said.
For more information go to www.parkinsonresearchfoundation.org
Parkinson’s disease progresses more slowly in patients with naturally high levels of the acid which triggers gout, suggesting a possible new treatment for the disease.
Patients with high levels of uric acid were a third less likely to need treatment over the course of two years than those with low levels, the results of a new study show.
Researchers are now testing whether increasing Parkinson’s patients’ uric acid levels safely can help their condition.
An antioxidant, the acid is created naturally as we digest food.
But too much uric acid, or urate, can cause bouts of gout, an extremely painful joint condition, and kidney stones.
Diets rich in liver, seafood and dried beans have been linked to high uric acid levels but researchers warn that because of the side effects patients should not try to increase their urate levels themselves.
A smaller study published last year also suggested that high uric acid levels could slow the progression of Parkinson’s Disease.
Dr Alberto Ascherio, from the Harvard School of Public Health, who led the study, said: “Only now we can be reasonably sure that the slower rate of progression in patients with higher concentrations of urate is real and not a chance occurrence."
However, the researchers stress that they do not yet know if it is the acid itself which carries the protective benefit or some other process of the body which produces uric acid as a by-product.
The latest research looked at 800 sufferers of the condition.
The link between high uric acid levels and a slower development of the disease was less clear in women then men, the study found, however this may be because women tend to have higher natural levels of the acid.
The researchers are now conducting a trial to give 90 patients a drug, inosine, which can elevate uric acid levels, to test whether they can be safely raised and if this slows the speed of the disease.
"Because elevated urate levels have known health risks, including gout and kidney stones urate elevation should only be attempted in the context of a closely monitored clinical trial in which potential benefits and risks are carefully balanced," Dr Schwarzschild said.
For more information go to www.parkinsonresearchfoundation.org
Monday, January 4, 2010
Effects of chronic low dose rotenone treatment on human microglial cells
Author: Shamim ShaikhLouise Nicholson
Exposure to toxins / chemicals is considered to be a significant risk factor in the pathogenesis of Parkinson's disease (PD); one putative chemical is the naturally occurring herbicide rotenone that is now used widely in establishing PD models. We, and others, have shown that chronic low dose rotenone treatment induces excessive accumulation of Reactive Oxygen Species (ROS), inclusion body formation and apoptosis in dopaminergic neurons of animal and human origin.
Some studies have also suggested that microglia enhance the rotenone induced neurotoxicity. While the effects of rotenone on neurons are well established, there is little or no information available on the effect of rotenone on microglial cells, and especially cells of human origin.
The aim of the present study was to investigate the effects of chronic low dose rotenone treatment on human microglial CHME-5 cells.
Methods: We have shown previously that rotenone induced inclusion body formation in human dopaminergic SH-SY5Y cells and therefore used these cells as a control for inclusion body formation in this study. SH-SY5Y and CHME-5 cells were treated with 5nM rotenone for four weeks.
At the end of week 4, both cell types were analysed for the presence of inclusion bodies, superoxide dismutases and cell activation (only in CHME-5 cells) using Haematoxylin and Eosin staining, immunocytochemical and western blotting methods. Levels of active caspases and ROS (both extra and intra cellular) were measured using biochemical methods.
Conclusion: The results suggest that chronic low dose rotenone treatment activates human microglia (cell line) in a manner similar to microglia of animal origin as shown by others.
However human microglia release excessive amounts of ROS extracellularly, do not show excessive amounts of intracellular ROS and active caspases and most importantly do not show any protein aggregation or inclusion body formation. Human microglia appear to be resistant to rotenone (chronic, low dose) induced damage.
For more information go to www.parkinsonresearchfoundation.org
Exposure to toxins / chemicals is considered to be a significant risk factor in the pathogenesis of Parkinson's disease (PD); one putative chemical is the naturally occurring herbicide rotenone that is now used widely in establishing PD models. We, and others, have shown that chronic low dose rotenone treatment induces excessive accumulation of Reactive Oxygen Species (ROS), inclusion body formation and apoptosis in dopaminergic neurons of animal and human origin.
Some studies have also suggested that microglia enhance the rotenone induced neurotoxicity. While the effects of rotenone on neurons are well established, there is little or no information available on the effect of rotenone on microglial cells, and especially cells of human origin.
The aim of the present study was to investigate the effects of chronic low dose rotenone treatment on human microglial CHME-5 cells.
Methods: We have shown previously that rotenone induced inclusion body formation in human dopaminergic SH-SY5Y cells and therefore used these cells as a control for inclusion body formation in this study. SH-SY5Y and CHME-5 cells were treated with 5nM rotenone for four weeks.
At the end of week 4, both cell types were analysed for the presence of inclusion bodies, superoxide dismutases and cell activation (only in CHME-5 cells) using Haematoxylin and Eosin staining, immunocytochemical and western blotting methods. Levels of active caspases and ROS (both extra and intra cellular) were measured using biochemical methods.
Conclusion: The results suggest that chronic low dose rotenone treatment activates human microglia (cell line) in a manner similar to microglia of animal origin as shown by others.
However human microglia release excessive amounts of ROS extracellularly, do not show excessive amounts of intracellular ROS and active caspases and most importantly do not show any protein aggregation or inclusion body formation. Human microglia appear to be resistant to rotenone (chronic, low dose) induced damage.
For more information go to www.parkinsonresearchfoundation.org
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