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.
Showing posts with label movement disorder. Show all posts
Showing posts with label movement disorder. Show all posts
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."
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 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.
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.
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)
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."
Monday, July 20, 2009
Initial treatment for Parkinson's disease
No known treatment can stop or reverse the breakdown of nerve cells that causes Parkinson's disease. However, drugs can relieve many symptoms of the disease. Surgery also can be effective in a small number of people to treat symptoms of Parkinson's disease.
Treatment is different for every person, and the type of treatment you will need may change as the disease progresses. Your age, work status, family, and living situation can all affect decisions about when to begin treatment, what types of treatment to use, and when to make changes in treatment. As your medical condition changes, you may need regular adjustments in your treatment to balance quality-of-life issues, side effects of treatment, and treatment costs.
Parkinson's disease causes a wide range of symptoms and complications. This topic covers the overall management of the disease. This topic does not discuss managing specific symptoms.
Initial treatment
If your symptoms are mild, you may not need treatment for Parkinson's disease. Your doctor may wait to prescribe treatment with drugs until your symptoms begin to interfere with your daily activities. Additional treatment methods (such as exercise, physical therapy, and occupational therapy) can be helpful at all stages of Parkinson's disease to help you maintain your strength, mobility, and independence.
If you do need drugs at this point, there are several options. Levodopa is considered the "gold standard" of treatment for Parkinson's disease. But levodopa can have negative effects when used long-term. Because of this, dopamine agonists such as pramipexole and ropinirole often are used first. Other non-dopamine drugs may be used early in the course of the disease. These include amantadine, monoamine oxidase inhibitors (such as selegiline), and anticholinergics (such as trihexyphenidyl). As the disease progresses, levodopa will likely need to be added.
Early in the disease, it might be helpful to take pills with food to help with nausea, which may be caused by some medicines taken for Parkinson's disease. Later in the disease, taking the medicines at least one hour before meals (and at least two hours after meals) may help them work better.
Your doctor, other health professionals, or Parkinson's disease support groups can help you get emotional support and education about the illness. This is important both early and throughout the course of the disease.
Ongoing treatment
As Parkinson's disease progresses, the symptoms usually become more disabling. Most people develop mild to moderate tremor. Movement is often slow and limited due to muscular rigidity and the slowing down and loss of automatic and spontaneous movement (bradykinesia). Treatment in this stage is determined by weighing the severity of the symptoms against the side effects of drugs.
The symptoms of Parkinson's disease change as the disease progresses. Because of this, your doctor will adjust your drugs to deal with the symptoms as they appear. Levodopa is the most commonly used drug for Parkinson's disease. However, it may cause side effects with prolonged use or high dosages. Your doctor may prescribe dopamine agonists such as pramipexole or ropinirole to delay the point at which you need to begin taking levodopa. Studies have suggested that this may delay the onset of levodopa's side effects.234 Your doctor may also prescribe levodopa along with a dopamine agonist.
Treatment is different for every person, and the type of treatment you will need may change as the disease progresses. Your age, work status, family, and living situation can all affect decisions about when to begin treatment, what types of treatment to use, and when to make changes in treatment. As your medical condition changes, you may need regular adjustments in your treatment to balance quality-of-life issues, side effects of treatment, and treatment costs.
Parkinson's disease causes a wide range of symptoms and complications. This topic covers the overall management of the disease. This topic does not discuss managing specific symptoms.
Initial treatment
If your symptoms are mild, you may not need treatment for Parkinson's disease. Your doctor may wait to prescribe treatment with drugs until your symptoms begin to interfere with your daily activities. Additional treatment methods (such as exercise, physical therapy, and occupational therapy) can be helpful at all stages of Parkinson's disease to help you maintain your strength, mobility, and independence.
If you do need drugs at this point, there are several options. Levodopa is considered the "gold standard" of treatment for Parkinson's disease. But levodopa can have negative effects when used long-term. Because of this, dopamine agonists such as pramipexole and ropinirole often are used first. Other non-dopamine drugs may be used early in the course of the disease. These include amantadine, monoamine oxidase inhibitors (such as selegiline), and anticholinergics (such as trihexyphenidyl). As the disease progresses, levodopa will likely need to be added.
Early in the disease, it might be helpful to take pills with food to help with nausea, which may be caused by some medicines taken for Parkinson's disease. Later in the disease, taking the medicines at least one hour before meals (and at least two hours after meals) may help them work better.
Your doctor, other health professionals, or Parkinson's disease support groups can help you get emotional support and education about the illness. This is important both early and throughout the course of the disease.
Ongoing treatment
As Parkinson's disease progresses, the symptoms usually become more disabling. Most people develop mild to moderate tremor. Movement is often slow and limited due to muscular rigidity and the slowing down and loss of automatic and spontaneous movement (bradykinesia). Treatment in this stage is determined by weighing the severity of the symptoms against the side effects of drugs.
The symptoms of Parkinson's disease change as the disease progresses. Because of this, your doctor will adjust your drugs to deal with the symptoms as they appear. Levodopa is the most commonly used drug for Parkinson's disease. However, it may cause side effects with prolonged use or high dosages. Your doctor may prescribe dopamine agonists such as pramipexole or ropinirole to delay the point at which you need to begin taking levodopa. Studies have suggested that this may delay the onset of levodopa's side effects.234 Your doctor may also prescribe levodopa along with a dopamine agonist.
Monday, July 13, 2009
Oxford Biomedica says study of ProSavin Parkinson’s treatment progressing well
Gene therapy group Oxford Biomedica PLC (AIM: OXB) said the Phase I/II study of its novel gene therapy, ProSavin, for the treatment of Parkinson's disease is progressing well.
Patients treated at the first dose level have maintained their improvement in motor function for one year, with an average improvement of 29 percent. Analogous investigator assessments of patients in the second cohort treated at a higher dose level have achieved similar benefit at three months, and the first patient to reach their six-month assessment has demonstrated further improvement.
The independent data monitoring committee supported Oxford BioMedica's proposal to proceed to a third dose level incorporating the company's new administration technology.
The ongoing Phase I/II study is designed to evaluate the safety and efficacy of ProSavin in patients with mid-stage Parkinson's disease who are experiencing reduced benefit on L-DOPA 'equivalent' therapy.
ProSavin is administered directly into the striatum of the brain using a well established surgical technique. The first stage of the study is a dose escalation in cohorts of three patients at each dose level and, to date, six patients have been treated.
ProSavin has been safe and well tolerated in all patients, with no serious adverse events and no evidence of immunotoxicity. All patients have reduced or maintained their PD medication relative to baseline.
The monitoring committee supports the company's proposal to proceed directly to a third dose level that is five-fold higher than the first dose level. Oxford Biomedica will incorporate its new delivery technology for the administration of the 5x dose level of ProSavin.
The new technique reduces the surgical time, facilitates higher dosing and has the potential to provide better reproducibility as study centres expand and thus accelerate clinical development timelines. A protocol amendment for the new technology is being prepared, which it plans to submit to French healthcare regulatory agency, AFSSAPS, before the end of the third quarter of 2009.
Patients treated at the first dose level have maintained their improvement in motor function for one year, with an average improvement of 29 percent. Analogous investigator assessments of patients in the second cohort treated at a higher dose level have achieved similar benefit at three months, and the first patient to reach their six-month assessment has demonstrated further improvement.
The independent data monitoring committee supported Oxford BioMedica's proposal to proceed to a third dose level incorporating the company's new administration technology.
The ongoing Phase I/II study is designed to evaluate the safety and efficacy of ProSavin in patients with mid-stage Parkinson's disease who are experiencing reduced benefit on L-DOPA 'equivalent' therapy.
ProSavin is administered directly into the striatum of the brain using a well established surgical technique. The first stage of the study is a dose escalation in cohorts of three patients at each dose level and, to date, six patients have been treated.
ProSavin has been safe and well tolerated in all patients, with no serious adverse events and no evidence of immunotoxicity. All patients have reduced or maintained their PD medication relative to baseline.
The monitoring committee supports the company's proposal to proceed directly to a third dose level that is five-fold higher than the first dose level. Oxford Biomedica will incorporate its new delivery technology for the administration of the 5x dose level of ProSavin.
The new technique reduces the surgical time, facilitates higher dosing and has the potential to provide better reproducibility as study centres expand and thus accelerate clinical development timelines. A protocol amendment for the new technology is being prepared, which it plans to submit to French healthcare regulatory agency, AFSSAPS, before the end of the third quarter of 2009.
Saturday, June 6, 2009
Creatine and Possible Benefits to Parkinson’s Disease Victims
Creatine, also known as creatine monohydrate, creatine phosphate or creatine citrate, is a naturally occurring amino acid compound in your body that is made by your liver and facilitates the production of energy in your body. Most of the creatine is stored in your skeletal muscles and the rest is found in your brain, heart and testes. You can eat foods that have creatine, such as red meat and fish. However, creatine is also available in supplement form through health food and drug stores.
Promoted in supplement form as an energy enhancement, creatine use is encouraged by the exercise and bodybuilding industries to increase exercise performance. It is this long-standing benefit that has lead scientists to organize large-scale national clinical trials of the product to determine if creatine can have a beneficial effect on symptoms of Parkinson’s disease. Classified by the Food and Drug Administration (FDA) as a nutritional supplement, creatine is widely used by professional athletes and is considered safe for daily supplemental use.
Researchers have also concluded that creatine increases the available energy for brain nerve cells and that this process helps prevent the loss of mitochondria. As a result it has positive effect on the health and survival of your nerve cell. Recognizing that an increase in cellular energy is beneficial to the health of your nerve cells, researchers believe that the addition of creatine to the diet will prevent injury and the premature death of the neurotransmitters and cells of your brain that are affected by Parkinson’s disease.
The symptoms of Parkinson’s, progressively uncontrollable shaking of the limbs and degeneration in the ability to speak, result from a reduction of dopamine in the brain. Dopamine is a neurotransmitter, which helps control movement. It is the hope of researchers that the introduction of creatine will increase the neurological response between brain cells and result in a potential treatment for the sufferers of Parkinson’s disease.
In prior 18 month clinical trials of several potential Parkinson’s treatments, in which the trials were designed to eliminate those that are proven to be futile, results indicated that creatine being noted as warranting of further large scale clinical study for efficacy. Researchers also noted that creatine was well tolerated by test subjects. Prior research on creatine, unrelated to study of Parkinson’s disease or its treatment, have also resulted in no long term or serious side effects.
The research studies to determine whether creatine will be instrumental in arresting the progression of Parkinson’s disease will last for 5 to 7 years. The subjects will be those that have been diagnosed with Parkinson’s in the last five years and have been treated for two years or less with drugs that increase the levels of dopamine in the brain. Additional benefits of creatine, which have researchers optimistic in the study outcome, include its antioxidant properties that have been shown to prevent brain cell loss in laboratory mice that are affected with Parkinson’s disease. Researchers are encouraged by this revelation, and hope to prove the same effects of creatine to be present in human test subjects.
Promoted in supplement form as an energy enhancement, creatine use is encouraged by the exercise and bodybuilding industries to increase exercise performance. It is this long-standing benefit that has lead scientists to organize large-scale national clinical trials of the product to determine if creatine can have a beneficial effect on symptoms of Parkinson’s disease. Classified by the Food and Drug Administration (FDA) as a nutritional supplement, creatine is widely used by professional athletes and is considered safe for daily supplemental use.
Researchers have also concluded that creatine increases the available energy for brain nerve cells and that this process helps prevent the loss of mitochondria. As a result it has positive effect on the health and survival of your nerve cell. Recognizing that an increase in cellular energy is beneficial to the health of your nerve cells, researchers believe that the addition of creatine to the diet will prevent injury and the premature death of the neurotransmitters and cells of your brain that are affected by Parkinson’s disease.
The symptoms of Parkinson’s, progressively uncontrollable shaking of the limbs and degeneration in the ability to speak, result from a reduction of dopamine in the brain. Dopamine is a neurotransmitter, which helps control movement. It is the hope of researchers that the introduction of creatine will increase the neurological response between brain cells and result in a potential treatment for the sufferers of Parkinson’s disease.
In prior 18 month clinical trials of several potential Parkinson’s treatments, in which the trials were designed to eliminate those that are proven to be futile, results indicated that creatine being noted as warranting of further large scale clinical study for efficacy. Researchers also noted that creatine was well tolerated by test subjects. Prior research on creatine, unrelated to study of Parkinson’s disease or its treatment, have also resulted in no long term or serious side effects.
The research studies to determine whether creatine will be instrumental in arresting the progression of Parkinson’s disease will last for 5 to 7 years. The subjects will be those that have been diagnosed with Parkinson’s in the last five years and have been treated for two years or less with drugs that increase the levels of dopamine in the brain. Additional benefits of creatine, which have researchers optimistic in the study outcome, include its antioxidant properties that have been shown to prevent brain cell loss in laboratory mice that are affected with Parkinson’s disease. Researchers are encouraged by this revelation, and hope to prove the same effects of creatine to be present in human test subjects.
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