by Lauren Hammit
A novel technique created at UCSF to deliver a growth factor directly to brain cells has shown promising results in treating Parkinson’s symptoms and could enter human clinical trials as early as next year.
The technique is part of an experimental treatment called gene therapy, which is considered a hopeful medical advance for neurodegenerative diseases such as Parkinson’s. Gene therapy involves introducing genetic material into a cell to cause the expression of a particular protein that can replace a missing or defective protein responsible for disease.
The UCSF team demonstrated for the first time that the infusion system they designed successfully spread a targeted protein to critical regions in the primate brain. This resulted, on average, in a 50 percent improvement of symptoms that continued out to two years.
“The approach is among the first shown to be beneficial to animals after they have already developed signs of Parkinson’s,” said Krystof Bankiewicz, MD, PhD, Kinetics Foundation Chair in Translational Research and professor of Neurological Surgery at UCSF. “Our ultimate goal is to reverse this disease in patients, and we hope this method will enable doctors to do exactly that.”
Findings are published online and in the July 14, 2010, issue of the Journal of Neuroscience.
In addition to an improvement in Parkinson’s symptoms, the treated animals also maintained a higher density of neurons that produce the brain chemical dopamine – the same neurons that disappear in Parkinson’s disease. Live imaging of the brain by positron emission tomography (PET) scanning, which has been used to gauge treatment effects in clinical studies of Parkinson’s, showed that those neurons remained active.
“The scans enabled us to see where the protein went – and just as hoped, it had been taken up by neurons and transported along nerve fibers to where it was needed, the substantia nigra.” Bankiewicz said. Parkinson’s disease attacks the substantia nigra, which is a part of the brain that controls movement.
A clinical trial is planned to test the safety of the method, according to the National Institutes of Neurological Disorders and Stroke, which funded this research. In a workup for the trial, the National Institutes of Health Rapid Access to Interventional Development (NIH RAID) program is supporting additional toxicity studies, as well as the production of clinical grade virus.
Showing posts with label dopamine. Show all posts
Showing posts with label dopamine. Show all posts
Saturday, July 24, 2010
Saturday, July 17, 2010
Treatments and drugs
By Mayo Clinic staff
There's no cure for Parkinson's disease, but medications can help control some of the symptoms of Parkinson's disease, and in some case, surgery may be helpful. Your doctor may recommend lifestyle changes, such as physical therapy, a healthy diet and exercise, in addition to medications.
Medications
Medications can help manage problems with walking, movement and tremor by increasing the brain's supply of dopamine. However, taking dopamine itself is not helpful, because it's unable to enter your brain.
Your initial response to Parkinson's treatment can be dramatic. Over time, however, the benefits of drugs frequently diminish or become less consistent, although symptoms can usually still be fairly well controlled.
Examples of medication your doctor may prescribe include:
Levodopa. The most effective Parkinson's drug is levodopa, which is a natural substance in the body. When taken by mouth in pill form, it passes into the brain and is converted to dopamine. Levodopa is combined with carbidopa to create the combination drug, Sinemet. The carbidopa protects levodopa from premature conversion to dopamine outside the brain; in doing that, it also prevents nausea. In Europe, levodopa is combined with a similar substance, benserazide, and is marketed as Madopar.
As the disease progresses, the benefit from levodopa may become less stable, with a tendency to wax and wane ("wearing off"). This then requires medication adjustments. Levodopa side effects include involuntary movements called dyskinesia. These resolve with dose reduction, but sometimes at the expense of reduced parkinsonism control. Like other Parkinson's drugs, it may also lower your blood pressure when standing.
Dopamine agonists. Unlike levodopa, these drugs aren't changed into dopamine. Instead, they mimic the effects of dopamine in the brain and cause neurons to react as though dopamine is present. They are not nearly as effective in treating the symptoms of Parkinson's disease. However, they last longer and are often used to smooth the sometimes off-and-on effect of levodopa.
This class includes pill forms of dopamine agonists, such as pramipexole (Mirapex) and ropinirole (Requip). A short-acting injectable dopamine agonist, apomorphine (Apokyn), is used for quick relief.
The side effects of dopamine agonists include hallucinations, sleepiness, water retention and low blood pressure when standing. These medications may also increase your risk of compulsive behaviors such as hypersexuality, compulsive gambling and compulsive overeating. If you are taking these medications and start behaving in a way that's out of character for you, talk to your doctor.
* MAO B inhibitors. These types of drugs, including selegiline (Eldepryl) and rasagiline (Azilect), help prevent the breakdown of both naturally occurring dopamine and dopamine formed from levodopa. They do this by inhibiting the activity of the enzyme monoamine oxidase B (MAO B) — an enzyme that metabolizes dopamine in the brain. Side effects are rare but may include confusion, headache, hallucinations and dizziness. These medications can't be used in combination with other antidepressants, the antibiotic ciprofloxacin (Cipro), the herb St. John's wort or certain narcotics. Check with your doctor before taking any additional medications with an MAO inhibitor.
* Catechol O-methyltransferase (COMT) inhibitors. These drugs prolong the effect of carbidopa-levodopa therapy by blocking an enzyme that breaks down levodopa. Tolcapone (Tasmar) has been linked to liver damage and liver failure, so it's normally used only in people who aren't responding to other therapies. Entacapone (Comtan) doesn't cause liver problems and is now combined with carbidopa and levodopa in a medication called Stalevo. However, it may worsen other levodopa side effects, such as involuntary movements (dyskinesias), nausea, confusion or hallucinations. It may cause urine discoloration.
* Anticholinergics. These drugs have been used for many years to help control the tremor associated with Parkinson's disease. A number of anticholinergic drugs, such as benztropine (Cogentin) and trihexyphenidyl, are available. However, their modest benefits are often offset by side effects such as impaired memory, confusion, constipation, dry mouth and eyes, and impaired urination.
* Glutamate (NMDA) blocking drugs. Doctors may prescribe amantadine (Symmetrel) alone to provide short-term relief of mild, early-stage Parkinson's disease. It also may be added to carbidopa-levodopa therapy for people in the later stages of Parkinson's disease, especially if they have problems with involuntary movements (dyskinesia) induced by carbidopa-levodopa. Side effects include a purple mottling of the skin and, sometimes, hallucinations.
Physical therapy
Exercise is important for general health, but especially for maintaining function in Parkinson's disease. Physical therapy may be advisable and can help improve your mobility, range of motion and muscle tone. Although specific exercises can't stop the progress of the disease, maintaining muscle strength and agility can help counter some of the progressive tendencies of the disease and also allow you to feel more confident and capable. A physical therapist can also work with you to improve your gait and balance. A speech therapist or speech pathologist can improve problems with speaking and swallowing.
Surgery
Deep brain stimulation is a surgical procedure used to treat Parkinson's disease. It involves implanting an electrode deep within the parts of your brain that control movement. The amount of stimulation delivered by the electrode is controlled by a pacemaker-like device placed under the skin in your upper chest. A wire that travels under your skin connects the device, called a pulse generator, to the electrodes.
Deep brain stimulation is most often used for people with advanced Parkinson's disease who have unstable medication (levodopa) responses. It can stabilize medication fluctuations and reduce or eliminate involuntary movements (dyskinesia). Tremor is especially responsive to this therapy.
Serious risks of this procedure are uncommon, but include brain hemorrhage or stroke. Infection is also a risk, and sometimes requires parts of the device to be replaced. Deep brain stimulation isn't beneficial for people who don't respond to carbidopa-levodopa.
There's no cure for Parkinson's disease, but medications can help control some of the symptoms of Parkinson's disease, and in some case, surgery may be helpful. Your doctor may recommend lifestyle changes, such as physical therapy, a healthy diet and exercise, in addition to medications.
Medications
Medications can help manage problems with walking, movement and tremor by increasing the brain's supply of dopamine. However, taking dopamine itself is not helpful, because it's unable to enter your brain.
Your initial response to Parkinson's treatment can be dramatic. Over time, however, the benefits of drugs frequently diminish or become less consistent, although symptoms can usually still be fairly well controlled.
Examples of medication your doctor may prescribe include:
Levodopa. The most effective Parkinson's drug is levodopa, which is a natural substance in the body. When taken by mouth in pill form, it passes into the brain and is converted to dopamine. Levodopa is combined with carbidopa to create the combination drug, Sinemet. The carbidopa protects levodopa from premature conversion to dopamine outside the brain; in doing that, it also prevents nausea. In Europe, levodopa is combined with a similar substance, benserazide, and is marketed as Madopar.
As the disease progresses, the benefit from levodopa may become less stable, with a tendency to wax and wane ("wearing off"). This then requires medication adjustments. Levodopa side effects include involuntary movements called dyskinesia. These resolve with dose reduction, but sometimes at the expense of reduced parkinsonism control. Like other Parkinson's drugs, it may also lower your blood pressure when standing.
Dopamine agonists. Unlike levodopa, these drugs aren't changed into dopamine. Instead, they mimic the effects of dopamine in the brain and cause neurons to react as though dopamine is present. They are not nearly as effective in treating the symptoms of Parkinson's disease. However, they last longer and are often used to smooth the sometimes off-and-on effect of levodopa.
This class includes pill forms of dopamine agonists, such as pramipexole (Mirapex) and ropinirole (Requip). A short-acting injectable dopamine agonist, apomorphine (Apokyn), is used for quick relief.
The side effects of dopamine agonists include hallucinations, sleepiness, water retention and low blood pressure when standing. These medications may also increase your risk of compulsive behaviors such as hypersexuality, compulsive gambling and compulsive overeating. If you are taking these medications and start behaving in a way that's out of character for you, talk to your doctor.
* MAO B inhibitors. These types of drugs, including selegiline (Eldepryl) and rasagiline (Azilect), help prevent the breakdown of both naturally occurring dopamine and dopamine formed from levodopa. They do this by inhibiting the activity of the enzyme monoamine oxidase B (MAO B) — an enzyme that metabolizes dopamine in the brain. Side effects are rare but may include confusion, headache, hallucinations and dizziness. These medications can't be used in combination with other antidepressants, the antibiotic ciprofloxacin (Cipro), the herb St. John's wort or certain narcotics. Check with your doctor before taking any additional medications with an MAO inhibitor.
* Catechol O-methyltransferase (COMT) inhibitors. These drugs prolong the effect of carbidopa-levodopa therapy by blocking an enzyme that breaks down levodopa. Tolcapone (Tasmar) has been linked to liver damage and liver failure, so it's normally used only in people who aren't responding to other therapies. Entacapone (Comtan) doesn't cause liver problems and is now combined with carbidopa and levodopa in a medication called Stalevo. However, it may worsen other levodopa side effects, such as involuntary movements (dyskinesias), nausea, confusion or hallucinations. It may cause urine discoloration.
* Anticholinergics. These drugs have been used for many years to help control the tremor associated with Parkinson's disease. A number of anticholinergic drugs, such as benztropine (Cogentin) and trihexyphenidyl, are available. However, their modest benefits are often offset by side effects such as impaired memory, confusion, constipation, dry mouth and eyes, and impaired urination.
* Glutamate (NMDA) blocking drugs. Doctors may prescribe amantadine (Symmetrel) alone to provide short-term relief of mild, early-stage Parkinson's disease. It also may be added to carbidopa-levodopa therapy for people in the later stages of Parkinson's disease, especially if they have problems with involuntary movements (dyskinesia) induced by carbidopa-levodopa. Side effects include a purple mottling of the skin and, sometimes, hallucinations.
Physical therapy
Exercise is important for general health, but especially for maintaining function in Parkinson's disease. Physical therapy may be advisable and can help improve your mobility, range of motion and muscle tone. Although specific exercises can't stop the progress of the disease, maintaining muscle strength and agility can help counter some of the progressive tendencies of the disease and also allow you to feel more confident and capable. A physical therapist can also work with you to improve your gait and balance. A speech therapist or speech pathologist can improve problems with speaking and swallowing.
Surgery
Deep brain stimulation is a surgical procedure used to treat Parkinson's disease. It involves implanting an electrode deep within the parts of your brain that control movement. The amount of stimulation delivered by the electrode is controlled by a pacemaker-like device placed under the skin in your upper chest. A wire that travels under your skin connects the device, called a pulse generator, to the electrodes.
Deep brain stimulation is most often used for people with advanced Parkinson's disease who have unstable medication (levodopa) responses. It can stabilize medication fluctuations and reduce or eliminate involuntary movements (dyskinesia). Tremor is especially responsive to this therapy.
Serious risks of this procedure are uncommon, but include brain hemorrhage or stroke. Infection is also a risk, and sometimes requires parts of the device to be replaced. Deep brain stimulation isn't beneficial for people who don't respond to carbidopa-levodopa.
Saturday, July 10, 2010
Top Ten Things to Know About Stem Cell Treatments
by Juan Munevar
There are different types of stem cells—each with their own purpose.
There are many different types of stem cells that come from different places in the body or are formed at different times in our lives. These include embryonic stem cells that exist only at the earliest stages of development and various types of ‘tissue-specific’ or ‘adult’ stem cells that appear during fetal development and remain in our bodies throughout life.
Our bodies use different types of tissue-specific stem cells to fit a particular purpose. Tissue-specific stem cells are limited in their potential and largely make the cell types found in the tissue from which they are derived. For example, the blood-forming stem cells (or hematopoietic stem cells) in the bone marrow regenerate the blood, while neural stem cells in the brain make brain cells. A neural stem cell won’t spontaneously make a blood cell and likewise a hematopoietic stem cell won’t spontaneously make a brain cell. Thus, it is unlikely that a single cell type could be used to treat a multitude of unrelated diseases that involve different tissues or organs. Be wary of clinics that offer treatments with stem cells that originate from a part of the body that is different from the part being treated.
2. A single stem cell treatment will not work on a multitude of unrelated diseases or conditions.
As described above, each type of stem cell fulfills a specific function in the body and cannot be expected to make cell types from other tissues. Thus, it is unlikely that a single type of stem cell treatment can treat multiple unrelated conditions, such as diabetes and Parkinson’s disease. The underlying causes are very different and different cell types would need to be replaced to treat each condition. It is critical that the cell type used as a treatment be appropriate to the specific disease or condition.
Embryonic stem cells may one day be used to generate treatments for a range of human diseases. However, embryonic stem cells themselves cannot directly be used for therapies as they would likely cause tumors and are unlikely to become the cells needed to regenerate a tissue on their own. They would first need to be coaxed to develop into specialized cell types before transplantation. A major warning sign that a clinic may not be credible is when treatments are offered for a wide variety of conditions but rely on a single cell type.
3. Currently, there are very few widely accepted stem cell therapies.
The range of diseases where stem cell treatments have been shown to be beneficial in responsibly conducted clinical trials is still extremely restricted. The best defined and most extensively used is blood stem cell transplantation to treat diseases and conditions of the blood and immune system, or to restore the blood system after treatments for specific cancers. Some bone, skin and corneal diseases or injuries can be treated with grafting of tissue that depends upon stem cells from these organs. These therapies are also generally accepted as safe and effective by the medical community.
4. Just because people say stem cells helped them doesn’t mean they did.
There are three main reasons why a person might feel better that are unrelated to the actual stem cell treatment: the ‘placebo effect’, accompanying treatments, and natural fluctuations of the disease or condition. The intense desire or belief that a treatment will work can cause a person to feel like it has and to even experience positive physical changes, such as improved movement or less pain. This phenomenon is called the placebo effect. Even having a positive conversation with a doctor can cause a person to feel improvement. Likewise, other techniques offered along with stem cell treatment—such as changes to diet, relaxation, physical therapy, medication, etc.—may make a person feel better in a way that is unrelated to the stem cells. Also, the severity of symptoms of many conditions can change over time, resulting in either temporary improvement or decline, which can complicate the interpretation of the effectiveness of treatments. These factors are so widespread that without testing in a controlled clinical study, where a group that receives a treatment is carefully compared against a group that does not receive this treatment, it is very difficult to determine the real effect of any therapy. Be wary of clinics that measure or advertise their results primarily through patient testimonials.
5. A large part of why it takes time to develop new therapies is that science itself is a long and difficult process.
Science, in general, is a long and involved process. Understanding what goes wrong in disease or injury and how to fix it takes time. New ideas have to be tested first in a research laboratory, and many times the new ideas don’t work. Even once the basic science has been established, translating it into an effective medical treatment is a long and difficult process. Something that looks promising in cultured cells may fail as a therapy in an animal model and something that works in an animal model may fail when it is tried on humans. Once therapies are tested in humans, ensuring patient safety becomes a critical issue and this means starting with very few people until the safety and side effects are better understood.
6. To be used in treatments, stem cells will have to be instructed to behave in specific ways.
Bone marrow transplantation is typically successful because we are asking the cells to do exactly what they were designed to do, make more blood. For other conditions, we may want the cells to behave in ways that are different from how they would ordinarily work in the body. One of the greatest barriers to the development of successful stem cell therapies is to get the cells to behave in the desired way. Also, once transplanted inside the body the cells need to integrate and function in concert with the body’s other cells. For example, to treat many neurological conditions the cells we implant will need to grow into specific types of neurons, and to work they will also have to know which other neurons to make connections with and how to make these connections. We are still learning about how to direct stem cells to become the right cell type, to grow only as much as we need them to, and the best ways to transplant them. Discovering how to do all this will take time. Be wary of claims that stem cells will somehow just know where to go and what to do to treat a specific condition.
7. Just because stem cells came from your body doesn’t mean they are safe.
Every medical procedure has risks. While you are unlikely to have an immune response to your own cells, the procedures used to acquire, grow and deliver them are potentially risky. As soon as the cells leave your body they may be subjected to a number of manipulations that could change the characteristics of the cells. If they are grown in culture (a process called expansion), the cells may lose the normal mechanisms that control growth or may lose the ability to specialize into the cell types you need. The cells may become contaminated with bacteria, viruses or other pathogens that could cause disease. The procedure to either remove or inject the cells also carries risk, from introducing an infection to damaging the tissue into which they are injected.
8. There is something to lose by trying an unproven treatment.
Some of the conditions that clinics claim are treatable with stem cells are considered incurable by other means. It is easy to understand why people might feel they have nothing to lose from trying something even if it is unproven. However, there are very real risks of developing complications, both immediate and long-term, while the chance of experiencing a benefit is likely very low. In one publicized case, a young boy developed brain tumors as a result of a stem cell treatment. Participating in an unproven treatment may make a person ineligible to participate in upcoming clinical trials (see also number 9). Where cost is high, there may be long-term financial implications for patients, their families and communities. If travel is involved there are additional considerations, not the least of which is being away from family and friends.
9. An experimental treatment offered for sale is not the same as a clinical trial.
The fact that a procedure is experimental does not automatically mean that it is part of a research study or clinical trial. A responsible clinical trial can be characterized by a number of key features. There is preclinical data supporting that the treatment being tested is likely to be safe and effective. Before starting, there is oversight by an independent group such as an Institutional Review Board or medical ethics committee that protect patients’ rights, and in many countries the trial is assessed and approved by a national regulatory agency, such as the European Medicines Agency (EMA) or the U.S. Food and Drug Administration (FDA). The study itself is designed to answer specific questions about a new treatment or a new way of using current treatments, often with a control group to which the group of people receiving the new treatment is compared. Typically, the cost of the new treatment and trial monitoring is defrayed by the company developing the treatment or by local or national government funding. Beware of expensive treatments that have not passed successfully through clinical trials.
Responsibly-conducted clinical trials are critical to the development of new treatments as they allow us to learn whether these treatments are safe and effective. The ISSCR supports participation in responsible clinical trials after careful consideration of the issues highlighted on this site and in discussion with a trusted physician.
10. Stem cell science is constantly moving forward.
Stem cell science is extraordinarily promising. There have been great advances in treating diseases and conditions of the blood system using blood-forming stem cells, and these show us just how powerful stem cell therapies can be. Scientists all over the world are researching ways to harness stem cells and use them to learn more about, to diagnose, and to treat various diseases and conditions. Every day scientists are working on new ways to shape and control different types of stem cells in ways that are bringing us closer to developing new treatments. Many potential treatments are currently being tested in animal models and some have already been brought to clinical trials. In February 2010 the British company ReNeuron announced it had been approved to conduct a Phase I clinical trial of a neural stem cell treatment for stroke. The first embryonic stem cell-based treatment for acute spinal cord injury is currently under review by the U.S. Food and Drug Administration (FDA) and will hopefully move into clinical trials soon. Although it is sometimes hard to see, stem cell science is moving forward. We are tremendously optimistic that stem cell therapies will someday be available to treat a wide range of human diseases and conditions.
There are different types of stem cells—each with their own purpose.
There are many different types of stem cells that come from different places in the body or are formed at different times in our lives. These include embryonic stem cells that exist only at the earliest stages of development and various types of ‘tissue-specific’ or ‘adult’ stem cells that appear during fetal development and remain in our bodies throughout life.
Our bodies use different types of tissue-specific stem cells to fit a particular purpose. Tissue-specific stem cells are limited in their potential and largely make the cell types found in the tissue from which they are derived. For example, the blood-forming stem cells (or hematopoietic stem cells) in the bone marrow regenerate the blood, while neural stem cells in the brain make brain cells. A neural stem cell won’t spontaneously make a blood cell and likewise a hematopoietic stem cell won’t spontaneously make a brain cell. Thus, it is unlikely that a single cell type could be used to treat a multitude of unrelated diseases that involve different tissues or organs. Be wary of clinics that offer treatments with stem cells that originate from a part of the body that is different from the part being treated.
2. A single stem cell treatment will not work on a multitude of unrelated diseases or conditions.
As described above, each type of stem cell fulfills a specific function in the body and cannot be expected to make cell types from other tissues. Thus, it is unlikely that a single type of stem cell treatment can treat multiple unrelated conditions, such as diabetes and Parkinson’s disease. The underlying causes are very different and different cell types would need to be replaced to treat each condition. It is critical that the cell type used as a treatment be appropriate to the specific disease or condition.
Embryonic stem cells may one day be used to generate treatments for a range of human diseases. However, embryonic stem cells themselves cannot directly be used for therapies as they would likely cause tumors and are unlikely to become the cells needed to regenerate a tissue on their own. They would first need to be coaxed to develop into specialized cell types before transplantation. A major warning sign that a clinic may not be credible is when treatments are offered for a wide variety of conditions but rely on a single cell type.
3. Currently, there are very few widely accepted stem cell therapies.
The range of diseases where stem cell treatments have been shown to be beneficial in responsibly conducted clinical trials is still extremely restricted. The best defined and most extensively used is blood stem cell transplantation to treat diseases and conditions of the blood and immune system, or to restore the blood system after treatments for specific cancers. Some bone, skin and corneal diseases or injuries can be treated with grafting of tissue that depends upon stem cells from these organs. These therapies are also generally accepted as safe and effective by the medical community.
4. Just because people say stem cells helped them doesn’t mean they did.
There are three main reasons why a person might feel better that are unrelated to the actual stem cell treatment: the ‘placebo effect’, accompanying treatments, and natural fluctuations of the disease or condition. The intense desire or belief that a treatment will work can cause a person to feel like it has and to even experience positive physical changes, such as improved movement or less pain. This phenomenon is called the placebo effect. Even having a positive conversation with a doctor can cause a person to feel improvement. Likewise, other techniques offered along with stem cell treatment—such as changes to diet, relaxation, physical therapy, medication, etc.—may make a person feel better in a way that is unrelated to the stem cells. Also, the severity of symptoms of many conditions can change over time, resulting in either temporary improvement or decline, which can complicate the interpretation of the effectiveness of treatments. These factors are so widespread that without testing in a controlled clinical study, where a group that receives a treatment is carefully compared against a group that does not receive this treatment, it is very difficult to determine the real effect of any therapy. Be wary of clinics that measure or advertise their results primarily through patient testimonials.
5. A large part of why it takes time to develop new therapies is that science itself is a long and difficult process.
Science, in general, is a long and involved process. Understanding what goes wrong in disease or injury and how to fix it takes time. New ideas have to be tested first in a research laboratory, and many times the new ideas don’t work. Even once the basic science has been established, translating it into an effective medical treatment is a long and difficult process. Something that looks promising in cultured cells may fail as a therapy in an animal model and something that works in an animal model may fail when it is tried on humans. Once therapies are tested in humans, ensuring patient safety becomes a critical issue and this means starting with very few people until the safety and side effects are better understood.
6. To be used in treatments, stem cells will have to be instructed to behave in specific ways.
Bone marrow transplantation is typically successful because we are asking the cells to do exactly what they were designed to do, make more blood. For other conditions, we may want the cells to behave in ways that are different from how they would ordinarily work in the body. One of the greatest barriers to the development of successful stem cell therapies is to get the cells to behave in the desired way. Also, once transplanted inside the body the cells need to integrate and function in concert with the body’s other cells. For example, to treat many neurological conditions the cells we implant will need to grow into specific types of neurons, and to work they will also have to know which other neurons to make connections with and how to make these connections. We are still learning about how to direct stem cells to become the right cell type, to grow only as much as we need them to, and the best ways to transplant them. Discovering how to do all this will take time. Be wary of claims that stem cells will somehow just know where to go and what to do to treat a specific condition.
7. Just because stem cells came from your body doesn’t mean they are safe.
Every medical procedure has risks. While you are unlikely to have an immune response to your own cells, the procedures used to acquire, grow and deliver them are potentially risky. As soon as the cells leave your body they may be subjected to a number of manipulations that could change the characteristics of the cells. If they are grown in culture (a process called expansion), the cells may lose the normal mechanisms that control growth or may lose the ability to specialize into the cell types you need. The cells may become contaminated with bacteria, viruses or other pathogens that could cause disease. The procedure to either remove or inject the cells also carries risk, from introducing an infection to damaging the tissue into which they are injected.
8. There is something to lose by trying an unproven treatment.
Some of the conditions that clinics claim are treatable with stem cells are considered incurable by other means. It is easy to understand why people might feel they have nothing to lose from trying something even if it is unproven. However, there are very real risks of developing complications, both immediate and long-term, while the chance of experiencing a benefit is likely very low. In one publicized case, a young boy developed brain tumors as a result of a stem cell treatment. Participating in an unproven treatment may make a person ineligible to participate in upcoming clinical trials (see also number 9). Where cost is high, there may be long-term financial implications for patients, their families and communities. If travel is involved there are additional considerations, not the least of which is being away from family and friends.
9. An experimental treatment offered for sale is not the same as a clinical trial.
The fact that a procedure is experimental does not automatically mean that it is part of a research study or clinical trial. A responsible clinical trial can be characterized by a number of key features. There is preclinical data supporting that the treatment being tested is likely to be safe and effective. Before starting, there is oversight by an independent group such as an Institutional Review Board or medical ethics committee that protect patients’ rights, and in many countries the trial is assessed and approved by a national regulatory agency, such as the European Medicines Agency (EMA) or the U.S. Food and Drug Administration (FDA). The study itself is designed to answer specific questions about a new treatment or a new way of using current treatments, often with a control group to which the group of people receiving the new treatment is compared. Typically, the cost of the new treatment and trial monitoring is defrayed by the company developing the treatment or by local or national government funding. Beware of expensive treatments that have not passed successfully through clinical trials.
Responsibly-conducted clinical trials are critical to the development of new treatments as they allow us to learn whether these treatments are safe and effective. The ISSCR supports participation in responsible clinical trials after careful consideration of the issues highlighted on this site and in discussion with a trusted physician.
10. Stem cell science is constantly moving forward.
Stem cell science is extraordinarily promising. There have been great advances in treating diseases and conditions of the blood system using blood-forming stem cells, and these show us just how powerful stem cell therapies can be. Scientists all over the world are researching ways to harness stem cells and use them to learn more about, to diagnose, and to treat various diseases and conditions. Every day scientists are working on new ways to shape and control different types of stem cells in ways that are bringing us closer to developing new treatments. Many potential treatments are currently being tested in animal models and some have already been brought to clinical trials. In February 2010 the British company ReNeuron announced it had been approved to conduct a Phase I clinical trial of a neural stem cell treatment for stroke. The first embryonic stem cell-based treatment for acute spinal cord injury is currently under review by the U.S. Food and Drug Administration (FDA) and will hopefully move into clinical trials soon. Although it is sometimes hard to see, stem cell science is moving forward. We are tremendously optimistic that stem cell therapies will someday be available to treat a wide range of human diseases and conditions.
Tuesday, June 22, 2010
Report: Spine Stimulation May Benefit Parkinson’s Disease Patients
By Steven Marsh
Patients who have been diagnosed with Parkinson’s disease (PD) may have relief from symptoms associated with the condition in the near future, according to a study presented at the 2010 American Society for Stereotactical and Functional Neurosurgery.
In an effort to find potential treatments for individuals with the nervous system disorder, a team of researchers at Rhode Island Hospital conducted a series of exercises that stimulated the spinal cord on an animal model, which showed signs of PD. Because the findings displayed better motor function in the animal, the investigators tested the treatment with spinal cord simulation on a male patient aged 82 years.
While the individual wasn’t receiving any form of medication as treatment for the disorder, researchers used different frequencies of stimulation to determine if a human would experience similar results compared to the animal model.
The researchers discovered that high stimulation frequencies made it easier for the patient to walk, while low frequencies worsened PD side effects.
While the results of the study did give investigators some insight as to how to treat PD patients, clinical trials with a larger group of patients would be more beneficial to developing treatment.
Finding therapies for this disorder is growing in interest throughout the medical world, as QR Pharma and Massachusetts General Hospital have launched research to determine a way to block a protein associated the development of PD.ADNFCR-1960-ID-19845071-ADNFCR
Patients who have been diagnosed with Parkinson’s disease (PD) may have relief from symptoms associated with the condition in the near future, according to a study presented at the 2010 American Society for Stereotactical and Functional Neurosurgery.
In an effort to find potential treatments for individuals with the nervous system disorder, a team of researchers at Rhode Island Hospital conducted a series of exercises that stimulated the spinal cord on an animal model, which showed signs of PD. Because the findings displayed better motor function in the animal, the investigators tested the treatment with spinal cord simulation on a male patient aged 82 years.
While the individual wasn’t receiving any form of medication as treatment for the disorder, researchers used different frequencies of stimulation to determine if a human would experience similar results compared to the animal model.
The researchers discovered that high stimulation frequencies made it easier for the patient to walk, while low frequencies worsened PD side effects.
While the results of the study did give investigators some insight as to how to treat PD patients, clinical trials with a larger group of patients would be more beneficial to developing treatment.
Finding therapies for this disorder is growing in interest throughout the medical world, as QR Pharma and Massachusetts General Hospital have launched research to determine a way to block a protein associated the development of PD.ADNFCR-1960-ID-19845071-ADNFCR
Thursday, June 10, 2010
The Pharmacist's Perspective on Treatment of Early-Stage Parkinson's Disease
Jack J. Chen, PharmD, BCPS, CGP
The management of Parkinson's disease (PD) is complex and involves nonpharmacologic and pharmacologic interventions for motor and nonmotor symptoms (see accompanying article by Dr. Simuni). The aim of this article is to provide a greater understanding of PD, treatment risks and benefits, and new developments in treatment approach that will allow clinicians, pharmacists, and allied healthcare personnel to better educate and care for patients with PD.
As PD progresses from early to advanced stages, medication adjustments and increased numbers of medications should be expected. This article will focus on pharmacotherapy interventions for early-stage PD with an emphasis on safety and drug interactions. A discussion about early interventions in PD, outcomes, and healthcare costs is available elsewhere.[1] Discussions regarding advanced stage PD, management of motor complications, and pharmacotherapies for nonmotor symptoms of PD are beyond the scope of this article and are also available elsewhere.[2]
The Patient With Early-Stage PD
An individual with early-stage PD who has been recently diagnosed may present with motor symptoms and absence of functional impairment or mild functional impairment (eg, clumsiness of the hands, mild deterioration in performance of sports activities, a bothersome tremor, worsening of handwriting). An untreated patient with early-stage PD will have a Unified Parkinson's Disease Rating Scale (UPDRS) score of 20 to 30.
The current pharmacologic management paradigm for early-stage PD consists of initiating 1 drug (ie, monotherapy) to provide symptomatic benefit. Drug therapy is typically initiated to address functional impairment. However, with the publication of the Attenuation of Disease progression with Azilect Given Once-daily (ADAGIO) study data, initiation of rasagiline in recently diagnosed patients with early PD presenting without functional impairment is a plausible approach.
In early-stage PD, monoamine oxidase type B (MAO-B) inhibitors, dopamine agonists, and levodopa (with a decarboxylase inhibitor such as carbidopa) all provide a sufficient magnitude of therapeutic effect. In addition to providing relief of tremor, rigidity, and/or slowness of movement, pharmacotherapy can also improve nonmotor symptoms such as fatigue in early PD and can improve experiences of daily living. If other symptoms such as constipation, depression, sexual dysfunction, and sleep disorders are present, adjunctive therapies that specifically target the symptom should also be considered.
Pharmacotherapy for Early-Stage PD: Safety, Side Effects, Drug Interactions
Drug safety and treatment-emergent side effects play a major role in guiding the selection and adjustment of pharmacotherapy in PD. Healthcare professionals involved in the pharmacotherapy management and distribution spectrum of PD should be concerned about the overall safety of the medications in this population, the safety of polypharmacy regimens and their necessity (or lack thereof), drug interactions, and education of the patient and family about benefits and risks of the medication regimen. Pharmacists, in particular, are traditionally more focused on drug safety and interactions as well as on providing instructions on proper use of medications.
Levodopa
Levodopa provides a robust magnitude of symptom relief effects. In patients with early PD, common side effects of levodopa include nausea and somnolence. Of note, hallucinations and psychosis are more common in patients with advanced stage PD. There is concern about the gradual emergence of motor complications (such as dyskinesias and fluctuations) associated with dose escalation and treatment duration. Motor complications can arise quickly (within a few months) or slowly (after a year or more). Although there are risk factors (eg, levodopa dose and treatment duration, younger age), no method has been found to predict which patients will experience motor complications.
The development of levodopa-associated motor complications has a significant impact on clinicians, patients, and healthcare resources. Motor complications can be a challenge for clinicians to manage, can impair patient health-related quality of life, and can increase direct health costs. Independent researchers and pharmaceutical manufacturers have devoted time and resources toward understanding the pathophysiology of motor complications and developing interventions that have specific efficacy for motor complications (eg, apomorphine, entacapone, rasagiline, selegiline oral disintegrating tablets, and deep brain stimulation). Eventually all patients with PD will be prescribed levodopa; however, in patients with early PD, other medications are available to provide adequate symptom relief without the risk for motor complications.
Pramipexole, ropinirole, and rasagiline are also indicated as monotherapy for PD. Clinicians and patients should engage in discussions about the relative risks and benefits of levodopa therapy, and patients should be allowed to make informed decisions.
Dopamine Agonists
The dopamine agonists (pramipexole, ropinirole) provide sufficient symptomatic effects for patients with early-stage PD and are less likely to cause motor complications. Side effects that are encountered by patients with early PD include nausea, somnolence, edema of the extremities, orthostatic hypotension, and impulse control disorders (ICDs). Of note, hallucinations may occur in patients with early PD, but are more common in advanced stage PD or patients with cognitive impairment.
Postmarketing recognition of the potential for dopamine agonist-induced ICDs has attracted much concern among clinicians who treat PD. ICDs can be a source of financial and familial strain for the patient. Common examples include excessive gambling, preoccupation with pornography, overindulgence in purchasing unnecessary items, excessive hobbyism, and preoccupation with Internet activities. The prospect of this potentially disruptive side effect should be communicated to the patient and family. Dopamine agonist-associated ICDs are not dose related and can also develop in patients receiving low daily doses for restless legs syndrome.
MAO-B Inhibitors
The MAO-B inhibitors (rasagiline, selegiline) provide modest symptomatic relief in patients with early PD. Of the available MAO-B inhibitors, rasagiline is the only one with labeling approved by the US Food and Drug Administration for monotherapy in PD. In addition, data from the ADAGIO study (a large, randomized, controlled trial) suggest that early initiation of rasagiline in patients with PD and the absence of functional impairment confer more benefit than delaying therapy.
Rasagiline is well tolerated in patients with early PD. Treatment-emergent side effects are nonspecific and include flulike weakness and asthenia. Overall, rasagiline is notable for its lack of dopaminergic side effects (eg, nausea, orthostasis, somnolence). Postmarketing data indicate that rasagiline can be safely administered without regard to meal content of tyramine (eg, in foods such as aged cheeses, red wine, sauerkraut). Based on clinical pharmacology studies, tyramine restriction is no longer required or advocated by the FDA when rasagiline is initiated. Likewise, sympathomimetic amines (eg, ephedrine, phenylephrine, phenylpropanolamine, pseudoephedrine) and local anesthesia with sympathomimetic vasoconstrictors can be administered concomitantly. Although the concurrent use of antidepressants (with serotonergic activity) is not contraindicated, benefits should be weighed against the potential for serotonin syndrome. The STACCATO study is underway to better define the potential occurrence of serotonin syndrome with rasagiline and antidepressants.[3]
Patient and Family Education
Patient and family education is critical for the safe and successful use of medications in patients with PD. The patient/family should be counseled about the adverse effects that are most likely to occur and when to report them to the prescriber. For example, ICDs such as Internet gambling could go undetected by family and unreported by patients and result in serious financial complications. Nausea, common with levodopa and dopamine agonists, is uncomfortable for patients, and in some circumstances, may cause discontinuation of therapy prematurely if patients are not informed in advance about how to manage the effect. The same is true for other adverse effects such as somnolence and orthostatic hypotension. Educating patients and family members about potential treatment-emergent side effects and the importance of seeking assistance can mitigate premature abandonment of the therapy and prevent the side effect from becoming more severe.
Patients and families should be counseled about the drug's expected time to onset and response. Levodopa symptomatic benefit will be noted almost immediately (within a few doses or days). Dopamine agonists require initiation at a low (subtherapeutic) dose with gradual titration to a maintenance dose. This is done to minimize side effects. Thus, onset of a noticeable improvement usually takes more than 2 weeks. The onset of noticeable improvement with rasagiline may take several weeks, and the full effect may not be seen for up to 8 to 12 weeks.
Lack of awareness regarding a realistic onset of effect can lead to medication abandonment (because of the belief that the drug is ineffective) and polypharmacy (if other agents are prescribed to treat symptoms that have not yet responded to the initial agent).
Patients and families should be counseled about the risks of self-discontinuing a drug for PD. A worsening of motor symptoms would occur, and in some cases, discontinuation effects such as agitation, anxiety, diaphoresis, dysphoria, insomnia, or neuroleptic malignant syndrome may occur.
Parkinson's disease is a lifelong neurologic disorder. Patients will be on pharmacotherapy for the rest of their lives and will have many encounters with professionals in healthcare. Early-stage, mildly impairing PD will progress over time to advanced stages, with severe motor impairment and nonmotor deficits. For patients with early-stage PD and their families, dealing with the diagnosis, learning about PD and its prognosis, and accepting the need for lifelong therapy can be overwhelming. Clinicians, pharmacists, and allied healthcare personnel can help patients and families dealing with PD by ensuring that they receive adequate medication information at the time a new prescription is written and again when it is dispensed. Patients should be assessed for side effects, and the need for ongoing monitoring of medication efficacy and potential side effects should be discussed with the family.
Summary
Patients with early-stage PD will have many encounters with healthcare professionals during their lifetime. A better understanding of the motor and nonmotor symptoms of PD, risks and benefits of PD medications (Table), and drug-related complications will allow clinicians, pharmacists, and allied health professionals to better educate and manage patients. Thoughtful consideration about the initiation of pharmacotherapy for early-stage PD and information on realistic expectations of efficacy and side effects can help prevent therapy abandonment and improve clinician-patient management of PD.
Supported by an independent educational grant from Teva Neuroscience.
The management of Parkinson's disease (PD) is complex and involves nonpharmacologic and pharmacologic interventions for motor and nonmotor symptoms (see accompanying article by Dr. Simuni). The aim of this article is to provide a greater understanding of PD, treatment risks and benefits, and new developments in treatment approach that will allow clinicians, pharmacists, and allied healthcare personnel to better educate and care for patients with PD.
As PD progresses from early to advanced stages, medication adjustments and increased numbers of medications should be expected. This article will focus on pharmacotherapy interventions for early-stage PD with an emphasis on safety and drug interactions. A discussion about early interventions in PD, outcomes, and healthcare costs is available elsewhere.[1] Discussions regarding advanced stage PD, management of motor complications, and pharmacotherapies for nonmotor symptoms of PD are beyond the scope of this article and are also available elsewhere.[2]
The Patient With Early-Stage PD
An individual with early-stage PD who has been recently diagnosed may present with motor symptoms and absence of functional impairment or mild functional impairment (eg, clumsiness of the hands, mild deterioration in performance of sports activities, a bothersome tremor, worsening of handwriting). An untreated patient with early-stage PD will have a Unified Parkinson's Disease Rating Scale (UPDRS) score of 20 to 30.
The current pharmacologic management paradigm for early-stage PD consists of initiating 1 drug (ie, monotherapy) to provide symptomatic benefit. Drug therapy is typically initiated to address functional impairment. However, with the publication of the Attenuation of Disease progression with Azilect Given Once-daily (ADAGIO) study data, initiation of rasagiline in recently diagnosed patients with early PD presenting without functional impairment is a plausible approach.
In early-stage PD, monoamine oxidase type B (MAO-B) inhibitors, dopamine agonists, and levodopa (with a decarboxylase inhibitor such as carbidopa) all provide a sufficient magnitude of therapeutic effect. In addition to providing relief of tremor, rigidity, and/or slowness of movement, pharmacotherapy can also improve nonmotor symptoms such as fatigue in early PD and can improve experiences of daily living. If other symptoms such as constipation, depression, sexual dysfunction, and sleep disorders are present, adjunctive therapies that specifically target the symptom should also be considered.
Pharmacotherapy for Early-Stage PD: Safety, Side Effects, Drug Interactions
Drug safety and treatment-emergent side effects play a major role in guiding the selection and adjustment of pharmacotherapy in PD. Healthcare professionals involved in the pharmacotherapy management and distribution spectrum of PD should be concerned about the overall safety of the medications in this population, the safety of polypharmacy regimens and their necessity (or lack thereof), drug interactions, and education of the patient and family about benefits and risks of the medication regimen. Pharmacists, in particular, are traditionally more focused on drug safety and interactions as well as on providing instructions on proper use of medications.
Levodopa
Levodopa provides a robust magnitude of symptom relief effects. In patients with early PD, common side effects of levodopa include nausea and somnolence. Of note, hallucinations and psychosis are more common in patients with advanced stage PD. There is concern about the gradual emergence of motor complications (such as dyskinesias and fluctuations) associated with dose escalation and treatment duration. Motor complications can arise quickly (within a few months) or slowly (after a year or more). Although there are risk factors (eg, levodopa dose and treatment duration, younger age), no method has been found to predict which patients will experience motor complications.
The development of levodopa-associated motor complications has a significant impact on clinicians, patients, and healthcare resources. Motor complications can be a challenge for clinicians to manage, can impair patient health-related quality of life, and can increase direct health costs. Independent researchers and pharmaceutical manufacturers have devoted time and resources toward understanding the pathophysiology of motor complications and developing interventions that have specific efficacy for motor complications (eg, apomorphine, entacapone, rasagiline, selegiline oral disintegrating tablets, and deep brain stimulation). Eventually all patients with PD will be prescribed levodopa; however, in patients with early PD, other medications are available to provide adequate symptom relief without the risk for motor complications.
Pramipexole, ropinirole, and rasagiline are also indicated as monotherapy for PD. Clinicians and patients should engage in discussions about the relative risks and benefits of levodopa therapy, and patients should be allowed to make informed decisions.
Dopamine Agonists
The dopamine agonists (pramipexole, ropinirole) provide sufficient symptomatic effects for patients with early-stage PD and are less likely to cause motor complications. Side effects that are encountered by patients with early PD include nausea, somnolence, edema of the extremities, orthostatic hypotension, and impulse control disorders (ICDs). Of note, hallucinations may occur in patients with early PD, but are more common in advanced stage PD or patients with cognitive impairment.
Postmarketing recognition of the potential for dopamine agonist-induced ICDs has attracted much concern among clinicians who treat PD. ICDs can be a source of financial and familial strain for the patient. Common examples include excessive gambling, preoccupation with pornography, overindulgence in purchasing unnecessary items, excessive hobbyism, and preoccupation with Internet activities. The prospect of this potentially disruptive side effect should be communicated to the patient and family. Dopamine agonist-associated ICDs are not dose related and can also develop in patients receiving low daily doses for restless legs syndrome.
MAO-B Inhibitors
The MAO-B inhibitors (rasagiline, selegiline) provide modest symptomatic relief in patients with early PD. Of the available MAO-B inhibitors, rasagiline is the only one with labeling approved by the US Food and Drug Administration for monotherapy in PD. In addition, data from the ADAGIO study (a large, randomized, controlled trial) suggest that early initiation of rasagiline in patients with PD and the absence of functional impairment confer more benefit than delaying therapy.
Rasagiline is well tolerated in patients with early PD. Treatment-emergent side effects are nonspecific and include flulike weakness and asthenia. Overall, rasagiline is notable for its lack of dopaminergic side effects (eg, nausea, orthostasis, somnolence). Postmarketing data indicate that rasagiline can be safely administered without regard to meal content of tyramine (eg, in foods such as aged cheeses, red wine, sauerkraut). Based on clinical pharmacology studies, tyramine restriction is no longer required or advocated by the FDA when rasagiline is initiated. Likewise, sympathomimetic amines (eg, ephedrine, phenylephrine, phenylpropanolamine, pseudoephedrine) and local anesthesia with sympathomimetic vasoconstrictors can be administered concomitantly. Although the concurrent use of antidepressants (with serotonergic activity) is not contraindicated, benefits should be weighed against the potential for serotonin syndrome. The STACCATO study is underway to better define the potential occurrence of serotonin syndrome with rasagiline and antidepressants.[3]
Patient and Family Education
Patient and family education is critical for the safe and successful use of medications in patients with PD. The patient/family should be counseled about the adverse effects that are most likely to occur and when to report them to the prescriber. For example, ICDs such as Internet gambling could go undetected by family and unreported by patients and result in serious financial complications. Nausea, common with levodopa and dopamine agonists, is uncomfortable for patients, and in some circumstances, may cause discontinuation of therapy prematurely if patients are not informed in advance about how to manage the effect. The same is true for other adverse effects such as somnolence and orthostatic hypotension. Educating patients and family members about potential treatment-emergent side effects and the importance of seeking assistance can mitigate premature abandonment of the therapy and prevent the side effect from becoming more severe.
Patients and families should be counseled about the drug's expected time to onset and response. Levodopa symptomatic benefit will be noted almost immediately (within a few doses or days). Dopamine agonists require initiation at a low (subtherapeutic) dose with gradual titration to a maintenance dose. This is done to minimize side effects. Thus, onset of a noticeable improvement usually takes more than 2 weeks. The onset of noticeable improvement with rasagiline may take several weeks, and the full effect may not be seen for up to 8 to 12 weeks.
Lack of awareness regarding a realistic onset of effect can lead to medication abandonment (because of the belief that the drug is ineffective) and polypharmacy (if other agents are prescribed to treat symptoms that have not yet responded to the initial agent).
Patients and families should be counseled about the risks of self-discontinuing a drug for PD. A worsening of motor symptoms would occur, and in some cases, discontinuation effects such as agitation, anxiety, diaphoresis, dysphoria, insomnia, or neuroleptic malignant syndrome may occur.
Parkinson's disease is a lifelong neurologic disorder. Patients will be on pharmacotherapy for the rest of their lives and will have many encounters with professionals in healthcare. Early-stage, mildly impairing PD will progress over time to advanced stages, with severe motor impairment and nonmotor deficits. For patients with early-stage PD and their families, dealing with the diagnosis, learning about PD and its prognosis, and accepting the need for lifelong therapy can be overwhelming. Clinicians, pharmacists, and allied healthcare personnel can help patients and families dealing with PD by ensuring that they receive adequate medication information at the time a new prescription is written and again when it is dispensed. Patients should be assessed for side effects, and the need for ongoing monitoring of medication efficacy and potential side effects should be discussed with the family.
Summary
Patients with early-stage PD will have many encounters with healthcare professionals during their lifetime. A better understanding of the motor and nonmotor symptoms of PD, risks and benefits of PD medications (Table), and drug-related complications will allow clinicians, pharmacists, and allied health professionals to better educate and manage patients. Thoughtful consideration about the initiation of pharmacotherapy for early-stage PD and information on realistic expectations of efficacy and side effects can help prevent therapy abandonment and improve clinician-patient management of PD.
Supported by an independent educational grant from Teva Neuroscience.
Saturday, June 13, 2009
Treatments and drugs
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. Your doctor may recommend lifestyle changes, such as physical therapy, a healthy diet and exercise, in addition to medications. In some cases, surgery may be helpful.
Medications
Medications can help manage problems with walking, movement and tremor by increasing the brain's supply of dopamine. Taking dopamine itself is not helpful, because it is unable to enter your brain.
*
Levodopa. The most effective Parkinson's drug is levodopa, which is a natural substance that we all have in our 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 confusion, delusions and hallucinations, as well as involuntary movements called dyskinesia. These resolve with dose reduction, but sometimes at the expense of reduced parkinsonism control.
*
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, pramipexole (Mirapex) and ropinirole (Requip), as well as a patch form, rotigotine (Neupro). Pergolide (Permax) has been withdrawn from the market because of its association with heart valve problems. A short-acting injectable dopamine agonist, apomorphine (Apokyn), is used for quick relief.
The side effects of dopamine agonists include those of carbidopa-levodopa, although they're less likely to cause involuntary movements. However, they are substantially more likely to cause hallucinations, sleepiness or swelling. 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) — the enzyme that metabolizes dopamine in the brain. Side effects are rare but can include serious interactions with other medications, including drugs to treat depression and certain narcotics.
* 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.
* 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 trihexyphenidyl and benztropine (Cogentin), are available. However, their modest benefits may be offset by side effects such as confusion and hallucinations, particularly in people over the age of 70. Other side effects include dry mouth, nausea, urine retention — especially in men with an enlarged prostate — and severe constipation.
* Antivirals. 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 swollen ankles and a purple mottling of the skin.
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 mobility, range of motion and muscle tone. Although specific exercises can't stop the progress of the disease, improving muscle strength can help you 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 the most common surgical procedure 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 electrode.
Deep brain stimulation is most often used for people who have advanced Parkinson's disease who have unstable medication (levodopa) responses. It can stabilize medication fluctuations and reduce or eliminate involuntary movements (dyskinesias). Tremor is especially responsive to this therapy. Deep brain stimulation doesn't help dementia and may make that worse.
Like any other brain surgery, this procedure has risks — such as brain hemorrhage or stroke-like problems. Infection also may occur, requiring parts of the device to be replaced. In addition, the unit's battery beneath the skin of the chest wall must be surgically replaced every few years. Deep brain stimulation isn't beneficial for people who don't respond to carbidopa-levodopa.
Medications
Medications can help manage problems with walking, movement and tremor by increasing the brain's supply of dopamine. Taking dopamine itself is not helpful, because it is unable to enter your brain.
*
Levodopa. The most effective Parkinson's drug is levodopa, which is a natural substance that we all have in our 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 confusion, delusions and hallucinations, as well as involuntary movements called dyskinesia. These resolve with dose reduction, but sometimes at the expense of reduced parkinsonism control.
*
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, pramipexole (Mirapex) and ropinirole (Requip), as well as a patch form, rotigotine (Neupro). Pergolide (Permax) has been withdrawn from the market because of its association with heart valve problems. A short-acting injectable dopamine agonist, apomorphine (Apokyn), is used for quick relief.
The side effects of dopamine agonists include those of carbidopa-levodopa, although they're less likely to cause involuntary movements. However, they are substantially more likely to cause hallucinations, sleepiness or swelling. 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) — the enzyme that metabolizes dopamine in the brain. Side effects are rare but can include serious interactions with other medications, including drugs to treat depression and certain narcotics.
* 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.
* 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 trihexyphenidyl and benztropine (Cogentin), are available. However, their modest benefits may be offset by side effects such as confusion and hallucinations, particularly in people over the age of 70. Other side effects include dry mouth, nausea, urine retention — especially in men with an enlarged prostate — and severe constipation.
* Antivirals. 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 swollen ankles and a purple mottling of the skin.
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 mobility, range of motion and muscle tone. Although specific exercises can't stop the progress of the disease, improving muscle strength can help you 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 the most common surgical procedure 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 electrode.
Deep brain stimulation is most often used for people who have advanced Parkinson's disease who have unstable medication (levodopa) responses. It can stabilize medication fluctuations and reduce or eliminate involuntary movements (dyskinesias). Tremor is especially responsive to this therapy. Deep brain stimulation doesn't help dementia and may make that worse.
Like any other brain surgery, this procedure has risks — such as brain hemorrhage or stroke-like problems. Infection also may occur, requiring parts of the device to be replaced. In addition, the unit's battery beneath the skin of the chest wall must be surgically replaced every few years. Deep brain stimulation isn't beneficial for people who don't respond to carbidopa-levodopa.
Sunday, April 26, 2009
Studies Show 3 out of 4 Parkinson's Disease Patients Can Improve Walking and Quality of Life Within 2 Weeks
Studies Show 3 out of 4 Parkinson's Disease Patients Can Improve Walking and Quality of Life Within 2 Weeks
Newly released virtual reality gait training device shown to improve quality of life for Parkinson's disease and other movement disorders.
Haifa, Israel (PRWEB) April 13, 2009 -- Parkinson's disease patients are discovering first-hand that daily exercise with a new virtual reality device, the GaitAid, has a positive effect on their walking ability, minimizing balance problems and freezing, and improving quality of life. The GaitAid offers a drug free, non RX alternative with no side effects.
As soon as I tried it my mobility improved tremendously! For the first time in over a year I am already walking without a cane. I am so impressed and so grateful. I was dreading my planned trip out of the country until I received your glasses. I cannot wait to share the miracle with my friends who suffer from PD. Thank you!
Gait velocity and stride length were improved in PD patients after training with a visual-and-auditory virtual cueing system, with a marked residual effect. Devices utilizing closed-loop visual feedback system are desirable non-pharmacologic interventions to improve walking in PD.
Daniel Neal, a Parkinson's disease patient from Palm Springs, CA., commented after receiving his GaitAid, "As soon as I tried it my mobility improved tremendously! For the first time in over a year I am already walking without a cane. I am so impressed and so grateful. I was dreading my planned trip out of the country until I received your glasses. I cannot wait to share the miracle with my friends who suffer from PD. Thank you!"
Yoram Baram, a computer science professor and incumbent of the Roy Matas / Winnipeg Chair in Biomedical Engineering at the Technion, Israel Institute of Technology has collaborated with several neurologists specializing in treating Parkinson's disease, Multiple Sclerosis and other movement disorders, in developing and testing a new, non-invasive training device designed to proactively minimize freezing and balance problems during walking. The noticeable physical and mental improvement of patients participating in clinical studies led Baram to bring the GaitAid device to market as a FDA registered medical device and is offering the device for a no risk trial period on his company's website (www.medigait.com).
Alberto J. Espay, MD, from the Neuroscience Institute, Department of Neurology, Movement Disorders Center, University of Cincinnati, specializes in research and clinical treatment of movement disorders. After offering the GaitAid to a group of his Parkinson's disease patients to use at home, Dr. Espay states, "Gait velocity and stride length were improved in PD patients after training with a visual-and-auditory virtual cueing system, with a marked residual effect. Devices utilizing closed-loop visual feedback system are desirable non-pharmacologic interventions to improve walking in PD."
The easy to use device includes special glasses and earphones which provide sensory feedback in response to the patient's movements. A practice session involves walking with the device for up to twenty minutes with no special training needed. These practice sessions soon start to evoke a lasting improvement for most Parkinson's disease patients. The degree of improvement varies, some patients use the GaitAid only occasionally after a few months while others make a short session a part of their daily routine to keep their results.
Parkinson's disease remains a mystery of medical science. For reason's unknown, certain brain cells stop producing a substance called Dopamine, which affects an individual's movement, strength and balance. There is currently no cure, though stem cell research offers future promise.
Emerging scientific evidence confirms that movement lessens neurological deterioration that contributes to Parkinson's Disease progression.
The device is available for a no risk trial period of 60 days:
online www.medigait.com
email: support (at) medigait (dot) com
or by phone 888-777-9906.
Newly released virtual reality gait training device shown to improve quality of life for Parkinson's disease and other movement disorders.
Haifa, Israel (PRWEB) April 13, 2009 -- Parkinson's disease patients are discovering first-hand that daily exercise with a new virtual reality device, the GaitAid, has a positive effect on their walking ability, minimizing balance problems and freezing, and improving quality of life. The GaitAid offers a drug free, non RX alternative with no side effects.
As soon as I tried it my mobility improved tremendously! For the first time in over a year I am already walking without a cane. I am so impressed and so grateful. I was dreading my planned trip out of the country until I received your glasses. I cannot wait to share the miracle with my friends who suffer from PD. Thank you!
Gait velocity and stride length were improved in PD patients after training with a visual-and-auditory virtual cueing system, with a marked residual effect. Devices utilizing closed-loop visual feedback system are desirable non-pharmacologic interventions to improve walking in PD.
Daniel Neal, a Parkinson's disease patient from Palm Springs, CA., commented after receiving his GaitAid, "As soon as I tried it my mobility improved tremendously! For the first time in over a year I am already walking without a cane. I am so impressed and so grateful. I was dreading my planned trip out of the country until I received your glasses. I cannot wait to share the miracle with my friends who suffer from PD. Thank you!"
Yoram Baram, a computer science professor and incumbent of the Roy Matas / Winnipeg Chair in Biomedical Engineering at the Technion, Israel Institute of Technology has collaborated with several neurologists specializing in treating Parkinson's disease, Multiple Sclerosis and other movement disorders, in developing and testing a new, non-invasive training device designed to proactively minimize freezing and balance problems during walking. The noticeable physical and mental improvement of patients participating in clinical studies led Baram to bring the GaitAid device to market as a FDA registered medical device and is offering the device for a no risk trial period on his company's website (www.medigait.com).
Alberto J. Espay, MD, from the Neuroscience Institute, Department of Neurology, Movement Disorders Center, University of Cincinnati, specializes in research and clinical treatment of movement disorders. After offering the GaitAid to a group of his Parkinson's disease patients to use at home, Dr. Espay states, "Gait velocity and stride length were improved in PD patients after training with a visual-and-auditory virtual cueing system, with a marked residual effect. Devices utilizing closed-loop visual feedback system are desirable non-pharmacologic interventions to improve walking in PD."
The easy to use device includes special glasses and earphones which provide sensory feedback in response to the patient's movements. A practice session involves walking with the device for up to twenty minutes with no special training needed. These practice sessions soon start to evoke a lasting improvement for most Parkinson's disease patients. The degree of improvement varies, some patients use the GaitAid only occasionally after a few months while others make a short session a part of their daily routine to keep their results.
Parkinson's disease remains a mystery of medical science. For reason's unknown, certain brain cells stop producing a substance called Dopamine, which affects an individual's movement, strength and balance. There is currently no cure, though stem cell research offers future promise.
Emerging scientific evidence confirms that movement lessens neurological deterioration that contributes to Parkinson's Disease progression.
The device is available for a no risk trial period of 60 days:
online www.medigait.com
email: support (at) medigait (dot) com
or by phone 888-777-9906.
Saturday, March 14, 2009
Long Term Results Similar in Two Parkinson's Medications
By Will Dunham
WASHINGTON, March 9 (Reuters) - People with Parkinson's disease may worry over which of two kinds of medications to use when first starting treatment, but a study published on Monday indicates the results are similar either way.
Researchers compared disability levels and quality of life after six years for people who started out taking either the standard generic drug levodopa or privately held German drug maker Boehringer Ingelheim's Mirapex, also called pramipexole.
The two drugs are generally employed as the first line of treatment for Parkinson's disease. In different ways, they address the decline in production of the brain chemical dopamine that occurs with the disease.
Parkinson's undermines control over movements and speech. Patients can have stiffness or rigidity of the arms and legs, slowness or lack of movement, and walking difficulties, along with tremors in their hands, arms, legs, jaw or face.
Levodopa is seen as better to deal with mobility issues and tremors. But it can cause involuntary movements known as dyskinesia, and its effectiveness also may wear off over time.
Mirapex may be less effective at handling motor control symptoms and can cause sleepiness. But it is less likely to cause involuntary movements or lose effectiveness over time.
"Despite a little bit of variations in how people were doing in specific areas, in terms of overall quality of life and disability measurements, the two groups looked the same," University of Rochester Medical Center neurologist Dr. Kevin Biglan, one of the researchers, said in a telephone interview.
"Then it becomes more of an individual decision in terms of short-term issues and individual preferences about some of these complications, potentially," he said.
Mirapex is in a class of drugs called dopamine agonists that also includes GlaxoSmithKline's (GSK.L) (GSK.N) Requip, or ropinirole.
The researchers tracked 222 patients in the study published in the journal Archives of Neurology.
Of those who started on Mirapex, 90 percent of them ended up also taking levodopa, a drug that has been around for more than four decades, Biglan said. But the side effects differed depending on which drug they started on, he added.
"There's been all this research trying to address what's the better initial treatment strategy. And patients have struggled with whether they were making the right decision in terms of what treatment to go with initially," Biglan said.
"So they could probably make a decision regarding either treatment without being overly worried about the long-term implications," he added. Boehringer funded the study. (Editing by Julie Steenhuysen)
WASHINGTON, March 9 (Reuters) - People with Parkinson's disease may worry over which of two kinds of medications to use when first starting treatment, but a study published on Monday indicates the results are similar either way.
Researchers compared disability levels and quality of life after six years for people who started out taking either the standard generic drug levodopa or privately held German drug maker Boehringer Ingelheim's Mirapex, also called pramipexole.
The two drugs are generally employed as the first line of treatment for Parkinson's disease. In different ways, they address the decline in production of the brain chemical dopamine that occurs with the disease.
Parkinson's undermines control over movements and speech. Patients can have stiffness or rigidity of the arms and legs, slowness or lack of movement, and walking difficulties, along with tremors in their hands, arms, legs, jaw or face.
Levodopa is seen as better to deal with mobility issues and tremors. But it can cause involuntary movements known as dyskinesia, and its effectiveness also may wear off over time.
Mirapex may be less effective at handling motor control symptoms and can cause sleepiness. But it is less likely to cause involuntary movements or lose effectiveness over time.
"Despite a little bit of variations in how people were doing in specific areas, in terms of overall quality of life and disability measurements, the two groups looked the same," University of Rochester Medical Center neurologist Dr. Kevin Biglan, one of the researchers, said in a telephone interview.
"Then it becomes more of an individual decision in terms of short-term issues and individual preferences about some of these complications, potentially," he said.
Mirapex is in a class of drugs called dopamine agonists that also includes GlaxoSmithKline's (GSK.L) (GSK.N) Requip, or ropinirole.
The researchers tracked 222 patients in the study published in the journal Archives of Neurology.
Of those who started on Mirapex, 90 percent of them ended up also taking levodopa, a drug that has been around for more than four decades, Biglan said. But the side effects differed depending on which drug they started on, he added.
"There's been all this research trying to address what's the better initial treatment strategy. And patients have struggled with whether they were making the right decision in terms of what treatment to go with initially," Biglan said.
"So they could probably make a decision regarding either treatment without being overly worried about the long-term implications," he added. Boehringer funded the study. (Editing by Julie Steenhuysen)
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