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 experiments. Show all posts
Showing posts with label experiments. Show all posts
Tuesday, October 19, 2010
Thursday, August 12, 2010
Parkinson's Disease Placebo Response Increases with Expectations
Individuals with Parkinson's disease were more likely to have a neurochemical response to a placebo medication if they were told they had higher odds of receiving an active drug.
Chicago, IL - infoZine - "The promise of symptom improvement that is elicited by a placebo is a powerful modulator of brain neurochemistry," the authors write as background information to a report in the August issue of Archives of General Psychiatry, one of the JAMA/Archives journals. "Understanding the factors that modify the strength of the placebo effect is of major clinical as well as fundamental scientific significance." In patients with Parkinson's disease, the expectation of symptom improvement is associated with the release of the neurotransmitter dopamine, and the manipulation of this expectation has been shown to affect the motor performance of patients with the condition.
Sarah C. Lidstone, Ph.D., of Pacific Parkinson's Research Centre at Vancouver Coastal Health and the University of British Columbia, Vancouver, Canada, and colleagues studied 35 patients with mild to moderate Parkinson's disease undergoing treatment with the medication levodopa. On the first day of the study, a baseline positron emission tomographic (PET) scan was performed, participants were given levodopa and a second scan was performed one hour later to assess dopamine response. On the second day, patients were randomly assigned to one of four groups, during which they were told they had either a 25-percent, 50-percent, 75-percent or 100-percent chance of receiving active medication before the third scan; however, all patients were given placebo.
Patients who were told they had a 75-percent chance of receiving active medication demonstrated a significant release of dopamine in response to the placebo, whereas those in the other groups did not.
Patients' reactions to the active medication before the first scan was also correlated with their response to placebo. "Importantly, whereas prior medication experience (i.e., the dopaminergic response to levodopa) was the major determinant of dopamine release in the dorsal striatum, expectation of clinical improvement (i.e., the probability determined by group allocation) was additionally required to drive dopamine release in the ventral striatum," the authors write. Both areas have been shown to be involved with reward processing; in patients with a chronic debilitating illness who have responded to therapy in the past, expectation of therapeutic benefit in response to placebo has been likened to the expectation of receiving a reward.
"Our findings may have important implications for the design of clinical trials, as we have shown that both the probability of receiving active treatment—which varies in clinical trials depending on the study design and the information provided to the patient—as well as the treatment history of the patient influence dopamine system activity and consequently clinical outcome," the authors conclude. "While our finding of a biochemical placebo response restricted to a 75 percent likelihood of receiving active treatment may not generalize to diseases other than Parkinson's disease, it is extremely likely that both probability and prior experience have similarly profound effects in those conditions."
This study was funded by the Michael Smith Foundation for Health Research, the Canadian Institutes for Health Research and a TRIUMF Life Sciences Grant. Dr. Stoessl is supported by the Canada Research Chairs Program.
Chicago, IL - infoZine - "The promise of symptom improvement that is elicited by a placebo is a powerful modulator of brain neurochemistry," the authors write as background information to a report in the August issue of Archives of General Psychiatry, one of the JAMA/Archives journals. "Understanding the factors that modify the strength of the placebo effect is of major clinical as well as fundamental scientific significance." In patients with Parkinson's disease, the expectation of symptom improvement is associated with the release of the neurotransmitter dopamine, and the manipulation of this expectation has been shown to affect the motor performance of patients with the condition.
Sarah C. Lidstone, Ph.D., of Pacific Parkinson's Research Centre at Vancouver Coastal Health and the University of British Columbia, Vancouver, Canada, and colleagues studied 35 patients with mild to moderate Parkinson's disease undergoing treatment with the medication levodopa. On the first day of the study, a baseline positron emission tomographic (PET) scan was performed, participants were given levodopa and a second scan was performed one hour later to assess dopamine response. On the second day, patients were randomly assigned to one of four groups, during which they were told they had either a 25-percent, 50-percent, 75-percent or 100-percent chance of receiving active medication before the third scan; however, all patients were given placebo.
Patients who were told they had a 75-percent chance of receiving active medication demonstrated a significant release of dopamine in response to the placebo, whereas those in the other groups did not.
Patients' reactions to the active medication before the first scan was also correlated with their response to placebo. "Importantly, whereas prior medication experience (i.e., the dopaminergic response to levodopa) was the major determinant of dopamine release in the dorsal striatum, expectation of clinical improvement (i.e., the probability determined by group allocation) was additionally required to drive dopamine release in the ventral striatum," the authors write. Both areas have been shown to be involved with reward processing; in patients with a chronic debilitating illness who have responded to therapy in the past, expectation of therapeutic benefit in response to placebo has been likened to the expectation of receiving a reward.
"Our findings may have important implications for the design of clinical trials, as we have shown that both the probability of receiving active treatment—which varies in clinical trials depending on the study design and the information provided to the patient—as well as the treatment history of the patient influence dopamine system activity and consequently clinical outcome," the authors conclude. "While our finding of a biochemical placebo response restricted to a 75 percent likelihood of receiving active treatment may not generalize to diseases other than Parkinson's disease, it is extremely likely that both probability and prior experience have similarly profound effects in those conditions."
This study was funded by the Michael Smith Foundation for Health Research, the Canadian Institutes for Health Research and a TRIUMF Life Sciences Grant. Dr. Stoessl is supported by the Canada Research Chairs Program.
Saturday, July 24, 2010
UCSF Gene Therapy Method Allays Parkinson’s Symptoms
by Lauren Hammit
A novel technique created at UCSF to deliver a growth factor directly to brain cells has shown promising results in treating Parkinson’s symptoms and could enter human clinical trials as early as next year.
The technique is part of an experimental treatment called gene therapy, which is considered a hopeful medical advance for neurodegenerative diseases such as Parkinson’s. Gene therapy involves introducing genetic material into a cell to cause the expression of a particular protein that can replace a missing or defective protein responsible for disease.
The UCSF team demonstrated for the first time that the infusion system they designed successfully spread a targeted protein to critical regions in the primate brain. This resulted, on average, in a 50 percent improvement of symptoms that continued out to two years.
“The approach is among the first shown to be beneficial to animals after they have already developed signs of Parkinson’s,” said Krystof Bankiewicz, MD, PhD, Kinetics Foundation Chair in Translational Research and professor of Neurological Surgery at UCSF. “Our ultimate goal is to reverse this disease in patients, and we hope this method will enable doctors to do exactly that.”
Findings are published online and in the July 14, 2010, issue of the Journal of Neuroscience.
In addition to an improvement in Parkinson’s symptoms, the treated animals also maintained a higher density of neurons that produce the brain chemical dopamine – the same neurons that disappear in Parkinson’s disease. Live imaging of the brain by positron emission tomography (PET) scanning, which has been used to gauge treatment effects in clinical studies of Parkinson’s, showed that those neurons remained active.
“The scans enabled us to see where the protein went – and just as hoped, it had been taken up by neurons and transported along nerve fibers to where it was needed, the substantia nigra.” Bankiewicz said. Parkinson’s disease attacks the substantia nigra, which is a part of the brain that controls movement.
A clinical trial is planned to test the safety of the method, according to the National Institutes of Neurological Disorders and Stroke, which funded this research. In a workup for the trial, the National Institutes of Health Rapid Access to Interventional Development (NIH RAID) program is supporting additional toxicity studies, as well as the production of clinical grade virus.
A novel technique created at UCSF to deliver a growth factor directly to brain cells has shown promising results in treating Parkinson’s symptoms and could enter human clinical trials as early as next year.
The technique is part of an experimental treatment called gene therapy, which is considered a hopeful medical advance for neurodegenerative diseases such as Parkinson’s. Gene therapy involves introducing genetic material into a cell to cause the expression of a particular protein that can replace a missing or defective protein responsible for disease.
The UCSF team demonstrated for the first time that the infusion system they designed successfully spread a targeted protein to critical regions in the primate brain. This resulted, on average, in a 50 percent improvement of symptoms that continued out to two years.
“The approach is among the first shown to be beneficial to animals after they have already developed signs of Parkinson’s,” said Krystof Bankiewicz, MD, PhD, Kinetics Foundation Chair in Translational Research and professor of Neurological Surgery at UCSF. “Our ultimate goal is to reverse this disease in patients, and we hope this method will enable doctors to do exactly that.”
Findings are published online and in the July 14, 2010, issue of the Journal of Neuroscience.
In addition to an improvement in Parkinson’s symptoms, the treated animals also maintained a higher density of neurons that produce the brain chemical dopamine – the same neurons that disappear in Parkinson’s disease. Live imaging of the brain by positron emission tomography (PET) scanning, which has been used to gauge treatment effects in clinical studies of Parkinson’s, showed that those neurons remained active.
“The scans enabled us to see where the protein went – and just as hoped, it had been taken up by neurons and transported along nerve fibers to where it was needed, the substantia nigra.” Bankiewicz said. Parkinson’s disease attacks the substantia nigra, which is a part of the brain that controls movement.
A clinical trial is planned to test the safety of the method, according to the National Institutes of Neurological Disorders and Stroke, which funded this research. In a workup for the trial, the National Institutes of Health Rapid Access to Interventional Development (NIH RAID) program is supporting additional toxicity studies, as well as the production of clinical grade virus.
Saturday, July 17, 2010
Treatments and drugs
By Mayo Clinic staff
There's no cure for Parkinson's disease, but medications can help control some of the symptoms of Parkinson's disease, and in some case, surgery may be helpful. Your doctor may recommend lifestyle changes, such as physical therapy, a healthy diet and exercise, in addition to medications.
Medications
Medications can help manage problems with walking, movement and tremor by increasing the brain's supply of dopamine. However, taking dopamine itself is not helpful, because it's unable to enter your brain.
Your initial response to Parkinson's treatment can be dramatic. Over time, however, the benefits of drugs frequently diminish or become less consistent, although symptoms can usually still be fairly well controlled.
Examples of medication your doctor may prescribe include:
Levodopa. The most effective Parkinson's drug is levodopa, which is a natural substance in the body. When taken by mouth in pill form, it passes into the brain and is converted to dopamine. Levodopa is combined with carbidopa to create the combination drug, Sinemet. The carbidopa protects levodopa from premature conversion to dopamine outside the brain; in doing that, it also prevents nausea. In Europe, levodopa is combined with a similar substance, benserazide, and is marketed as Madopar.
As the disease progresses, the benefit from levodopa may become less stable, with a tendency to wax and wane ("wearing off"). This then requires medication adjustments. Levodopa side effects include involuntary movements called dyskinesia. These resolve with dose reduction, but sometimes at the expense of reduced parkinsonism control. Like other Parkinson's drugs, it may also lower your blood pressure when standing.
Dopamine agonists. Unlike levodopa, these drugs aren't changed into dopamine. Instead, they mimic the effects of dopamine in the brain and cause neurons to react as though dopamine is present. They are not nearly as effective in treating the symptoms of Parkinson's disease. However, they last longer and are often used to smooth the sometimes off-and-on effect of levodopa.
This class includes pill forms of dopamine agonists, such as pramipexole (Mirapex) and ropinirole (Requip). A short-acting injectable dopamine agonist, apomorphine (Apokyn), is used for quick relief.
The side effects of dopamine agonists include hallucinations, sleepiness, water retention and low blood pressure when standing. These medications may also increase your risk of compulsive behaviors such as hypersexuality, compulsive gambling and compulsive overeating. If you are taking these medications and start behaving in a way that's out of character for you, talk to your doctor.
* MAO B inhibitors. These types of drugs, including selegiline (Eldepryl) and rasagiline (Azilect), help prevent the breakdown of both naturally occurring dopamine and dopamine formed from levodopa. They do this by inhibiting the activity of the enzyme monoamine oxidase B (MAO B) — an enzyme that metabolizes dopamine in the brain. Side effects are rare but may include confusion, headache, hallucinations and dizziness. These medications can't be used in combination with other antidepressants, the antibiotic ciprofloxacin (Cipro), the herb St. John's wort or certain narcotics. Check with your doctor before taking any additional medications with an MAO inhibitor.
* Catechol O-methyltransferase (COMT) inhibitors. These drugs prolong the effect of carbidopa-levodopa therapy by blocking an enzyme that breaks down levodopa. Tolcapone (Tasmar) has been linked to liver damage and liver failure, so it's normally used only in people who aren't responding to other therapies. Entacapone (Comtan) doesn't cause liver problems and is now combined with carbidopa and levodopa in a medication called Stalevo. However, it may worsen other levodopa side effects, such as involuntary movements (dyskinesias), nausea, confusion or hallucinations. It may cause urine discoloration.
* Anticholinergics. These drugs have been used for many years to help control the tremor associated with Parkinson's disease. A number of anticholinergic drugs, such as benztropine (Cogentin) and trihexyphenidyl, are available. However, their modest benefits are often offset by side effects such as impaired memory, confusion, constipation, dry mouth and eyes, and impaired urination.
* Glutamate (NMDA) blocking drugs. Doctors may prescribe amantadine (Symmetrel) alone to provide short-term relief of mild, early-stage Parkinson's disease. It also may be added to carbidopa-levodopa therapy for people in the later stages of Parkinson's disease, especially if they have problems with involuntary movements (dyskinesia) induced by carbidopa-levodopa. Side effects include a purple mottling of the skin and, sometimes, hallucinations.
Physical therapy
Exercise is important for general health, but especially for maintaining function in Parkinson's disease. Physical therapy may be advisable and can help improve your mobility, range of motion and muscle tone. Although specific exercises can't stop the progress of the disease, maintaining muscle strength and agility can help counter some of the progressive tendencies of the disease and also allow you to feel more confident and capable. A physical therapist can also work with you to improve your gait and balance. A speech therapist or speech pathologist can improve problems with speaking and swallowing.
Surgery
Deep brain stimulation is a surgical procedure used to treat Parkinson's disease. It involves implanting an electrode deep within the parts of your brain that control movement. The amount of stimulation delivered by the electrode is controlled by a pacemaker-like device placed under the skin in your upper chest. A wire that travels under your skin connects the device, called a pulse generator, to the electrodes.
Deep brain stimulation is most often used for people with advanced Parkinson's disease who have unstable medication (levodopa) responses. It can stabilize medication fluctuations and reduce or eliminate involuntary movements (dyskinesia). Tremor is especially responsive to this therapy.
Serious risks of this procedure are uncommon, but include brain hemorrhage or stroke. Infection is also a risk, and sometimes requires parts of the device to be replaced. Deep brain stimulation isn't beneficial for people who don't respond to carbidopa-levodopa.
There's no cure for Parkinson's disease, but medications can help control some of the symptoms of Parkinson's disease, and in some case, surgery may be helpful. Your doctor may recommend lifestyle changes, such as physical therapy, a healthy diet and exercise, in addition to medications.
Medications
Medications can help manage problems with walking, movement and tremor by increasing the brain's supply of dopamine. However, taking dopamine itself is not helpful, because it's unable to enter your brain.
Your initial response to Parkinson's treatment can be dramatic. Over time, however, the benefits of drugs frequently diminish or become less consistent, although symptoms can usually still be fairly well controlled.
Examples of medication your doctor may prescribe include:
Levodopa. The most effective Parkinson's drug is levodopa, which is a natural substance in the body. When taken by mouth in pill form, it passes into the brain and is converted to dopamine. Levodopa is combined with carbidopa to create the combination drug, Sinemet. The carbidopa protects levodopa from premature conversion to dopamine outside the brain; in doing that, it also prevents nausea. In Europe, levodopa is combined with a similar substance, benserazide, and is marketed as Madopar.
As the disease progresses, the benefit from levodopa may become less stable, with a tendency to wax and wane ("wearing off"). This then requires medication adjustments. Levodopa side effects include involuntary movements called dyskinesia. These resolve with dose reduction, but sometimes at the expense of reduced parkinsonism control. Like other Parkinson's drugs, it may also lower your blood pressure when standing.
Dopamine agonists. Unlike levodopa, these drugs aren't changed into dopamine. Instead, they mimic the effects of dopamine in the brain and cause neurons to react as though dopamine is present. They are not nearly as effective in treating the symptoms of Parkinson's disease. However, they last longer and are often used to smooth the sometimes off-and-on effect of levodopa.
This class includes pill forms of dopamine agonists, such as pramipexole (Mirapex) and ropinirole (Requip). A short-acting injectable dopamine agonist, apomorphine (Apokyn), is used for quick relief.
The side effects of dopamine agonists include hallucinations, sleepiness, water retention and low blood pressure when standing. These medications may also increase your risk of compulsive behaviors such as hypersexuality, compulsive gambling and compulsive overeating. If you are taking these medications and start behaving in a way that's out of character for you, talk to your doctor.
* MAO B inhibitors. These types of drugs, including selegiline (Eldepryl) and rasagiline (Azilect), help prevent the breakdown of both naturally occurring dopamine and dopamine formed from levodopa. They do this by inhibiting the activity of the enzyme monoamine oxidase B (MAO B) — an enzyme that metabolizes dopamine in the brain. Side effects are rare but may include confusion, headache, hallucinations and dizziness. These medications can't be used in combination with other antidepressants, the antibiotic ciprofloxacin (Cipro), the herb St. John's wort or certain narcotics. Check with your doctor before taking any additional medications with an MAO inhibitor.
* Catechol O-methyltransferase (COMT) inhibitors. These drugs prolong the effect of carbidopa-levodopa therapy by blocking an enzyme that breaks down levodopa. Tolcapone (Tasmar) has been linked to liver damage and liver failure, so it's normally used only in people who aren't responding to other therapies. Entacapone (Comtan) doesn't cause liver problems and is now combined with carbidopa and levodopa in a medication called Stalevo. However, it may worsen other levodopa side effects, such as involuntary movements (dyskinesias), nausea, confusion or hallucinations. It may cause urine discoloration.
* Anticholinergics. These drugs have been used for many years to help control the tremor associated with Parkinson's disease. A number of anticholinergic drugs, such as benztropine (Cogentin) and trihexyphenidyl, are available. However, their modest benefits are often offset by side effects such as impaired memory, confusion, constipation, dry mouth and eyes, and impaired urination.
* Glutamate (NMDA) blocking drugs. Doctors may prescribe amantadine (Symmetrel) alone to provide short-term relief of mild, early-stage Parkinson's disease. It also may be added to carbidopa-levodopa therapy for people in the later stages of Parkinson's disease, especially if they have problems with involuntary movements (dyskinesia) induced by carbidopa-levodopa. Side effects include a purple mottling of the skin and, sometimes, hallucinations.
Physical therapy
Exercise is important for general health, but especially for maintaining function in Parkinson's disease. Physical therapy may be advisable and can help improve your mobility, range of motion and muscle tone. Although specific exercises can't stop the progress of the disease, maintaining muscle strength and agility can help counter some of the progressive tendencies of the disease and also allow you to feel more confident and capable. A physical therapist can also work with you to improve your gait and balance. A speech therapist or speech pathologist can improve problems with speaking and swallowing.
Surgery
Deep brain stimulation is a surgical procedure used to treat Parkinson's disease. It involves implanting an electrode deep within the parts of your brain that control movement. The amount of stimulation delivered by the electrode is controlled by a pacemaker-like device placed under the skin in your upper chest. A wire that travels under your skin connects the device, called a pulse generator, to the electrodes.
Deep brain stimulation is most often used for people with advanced Parkinson's disease who have unstable medication (levodopa) responses. It can stabilize medication fluctuations and reduce or eliminate involuntary movements (dyskinesia). Tremor is especially responsive to this therapy.
Serious risks of this procedure are uncommon, but include brain hemorrhage or stroke. Infection is also a risk, and sometimes requires parts of the device to be replaced. Deep brain stimulation isn't beneficial for people who don't respond to carbidopa-levodopa.
Saturday, July 10, 2010
Top Ten Things to Know About Stem Cell Treatments
by Juan Munevar
There are different types of stem cells—each with their own purpose.
There are many different types of stem cells that come from different places in the body or are formed at different times in our lives. These include embryonic stem cells that exist only at the earliest stages of development and various types of ‘tissue-specific’ or ‘adult’ stem cells that appear during fetal development and remain in our bodies throughout life.
Our bodies use different types of tissue-specific stem cells to fit a particular purpose. Tissue-specific stem cells are limited in their potential and largely make the cell types found in the tissue from which they are derived. For example, the blood-forming stem cells (or hematopoietic stem cells) in the bone marrow regenerate the blood, while neural stem cells in the brain make brain cells. A neural stem cell won’t spontaneously make a blood cell and likewise a hematopoietic stem cell won’t spontaneously make a brain cell. Thus, it is unlikely that a single cell type could be used to treat a multitude of unrelated diseases that involve different tissues or organs. Be wary of clinics that offer treatments with stem cells that originate from a part of the body that is different from the part being treated.
2. A single stem cell treatment will not work on a multitude of unrelated diseases or conditions.
As described above, each type of stem cell fulfills a specific function in the body and cannot be expected to make cell types from other tissues. Thus, it is unlikely that a single type of stem cell treatment can treat multiple unrelated conditions, such as diabetes and Parkinson’s disease. The underlying causes are very different and different cell types would need to be replaced to treat each condition. It is critical that the cell type used as a treatment be appropriate to the specific disease or condition.
Embryonic stem cells may one day be used to generate treatments for a range of human diseases. However, embryonic stem cells themselves cannot directly be used for therapies as they would likely cause tumors and are unlikely to become the cells needed to regenerate a tissue on their own. They would first need to be coaxed to develop into specialized cell types before transplantation. A major warning sign that a clinic may not be credible is when treatments are offered for a wide variety of conditions but rely on a single cell type.
3. Currently, there are very few widely accepted stem cell therapies.
The range of diseases where stem cell treatments have been shown to be beneficial in responsibly conducted clinical trials is still extremely restricted. The best defined and most extensively used is blood stem cell transplantation to treat diseases and conditions of the blood and immune system, or to restore the blood system after treatments for specific cancers. Some bone, skin and corneal diseases or injuries can be treated with grafting of tissue that depends upon stem cells from these organs. These therapies are also generally accepted as safe and effective by the medical community.
4. Just because people say stem cells helped them doesn’t mean they did.
There are three main reasons why a person might feel better that are unrelated to the actual stem cell treatment: the ‘placebo effect’, accompanying treatments, and natural fluctuations of the disease or condition. The intense desire or belief that a treatment will work can cause a person to feel like it has and to even experience positive physical changes, such as improved movement or less pain. This phenomenon is called the placebo effect. Even having a positive conversation with a doctor can cause a person to feel improvement. Likewise, other techniques offered along with stem cell treatment—such as changes to diet, relaxation, physical therapy, medication, etc.—may make a person feel better in a way that is unrelated to the stem cells. Also, the severity of symptoms of many conditions can change over time, resulting in either temporary improvement or decline, which can complicate the interpretation of the effectiveness of treatments. These factors are so widespread that without testing in a controlled clinical study, where a group that receives a treatment is carefully compared against a group that does not receive this treatment, it is very difficult to determine the real effect of any therapy. Be wary of clinics that measure or advertise their results primarily through patient testimonials.
5. A large part of why it takes time to develop new therapies is that science itself is a long and difficult process.
Science, in general, is a long and involved process. Understanding what goes wrong in disease or injury and how to fix it takes time. New ideas have to be tested first in a research laboratory, and many times the new ideas don’t work. Even once the basic science has been established, translating it into an effective medical treatment is a long and difficult process. Something that looks promising in cultured cells may fail as a therapy in an animal model and something that works in an animal model may fail when it is tried on humans. Once therapies are tested in humans, ensuring patient safety becomes a critical issue and this means starting with very few people until the safety and side effects are better understood.
6. To be used in treatments, stem cells will have to be instructed to behave in specific ways.
Bone marrow transplantation is typically successful because we are asking the cells to do exactly what they were designed to do, make more blood. For other conditions, we may want the cells to behave in ways that are different from how they would ordinarily work in the body. One of the greatest barriers to the development of successful stem cell therapies is to get the cells to behave in the desired way. Also, once transplanted inside the body the cells need to integrate and function in concert with the body’s other cells. For example, to treat many neurological conditions the cells we implant will need to grow into specific types of neurons, and to work they will also have to know which other neurons to make connections with and how to make these connections. We are still learning about how to direct stem cells to become the right cell type, to grow only as much as we need them to, and the best ways to transplant them. Discovering how to do all this will take time. Be wary of claims that stem cells will somehow just know where to go and what to do to treat a specific condition.
7. Just because stem cells came from your body doesn’t mean they are safe.
Every medical procedure has risks. While you are unlikely to have an immune response to your own cells, the procedures used to acquire, grow and deliver them are potentially risky. As soon as the cells leave your body they may be subjected to a number of manipulations that could change the characteristics of the cells. If they are grown in culture (a process called expansion), the cells may lose the normal mechanisms that control growth or may lose the ability to specialize into the cell types you need. The cells may become contaminated with bacteria, viruses or other pathogens that could cause disease. The procedure to either remove or inject the cells also carries risk, from introducing an infection to damaging the tissue into which they are injected.
8. There is something to lose by trying an unproven treatment.
Some of the conditions that clinics claim are treatable with stem cells are considered incurable by other means. It is easy to understand why people might feel they have nothing to lose from trying something even if it is unproven. However, there are very real risks of developing complications, both immediate and long-term, while the chance of experiencing a benefit is likely very low. In one publicized case, a young boy developed brain tumors as a result of a stem cell treatment. Participating in an unproven treatment may make a person ineligible to participate in upcoming clinical trials (see also number 9). Where cost is high, there may be long-term financial implications for patients, their families and communities. If travel is involved there are additional considerations, not the least of which is being away from family and friends.
9. An experimental treatment offered for sale is not the same as a clinical trial.
The fact that a procedure is experimental does not automatically mean that it is part of a research study or clinical trial. A responsible clinical trial can be characterized by a number of key features. There is preclinical data supporting that the treatment being tested is likely to be safe and effective. Before starting, there is oversight by an independent group such as an Institutional Review Board or medical ethics committee that protect patients’ rights, and in many countries the trial is assessed and approved by a national regulatory agency, such as the European Medicines Agency (EMA) or the U.S. Food and Drug Administration (FDA). The study itself is designed to answer specific questions about a new treatment or a new way of using current treatments, often with a control group to which the group of people receiving the new treatment is compared. Typically, the cost of the new treatment and trial monitoring is defrayed by the company developing the treatment or by local or national government funding. Beware of expensive treatments that have not passed successfully through clinical trials.
Responsibly-conducted clinical trials are critical to the development of new treatments as they allow us to learn whether these treatments are safe and effective. The ISSCR supports participation in responsible clinical trials after careful consideration of the issues highlighted on this site and in discussion with a trusted physician.
10. Stem cell science is constantly moving forward.
Stem cell science is extraordinarily promising. There have been great advances in treating diseases and conditions of the blood system using blood-forming stem cells, and these show us just how powerful stem cell therapies can be. Scientists all over the world are researching ways to harness stem cells and use them to learn more about, to diagnose, and to treat various diseases and conditions. Every day scientists are working on new ways to shape and control different types of stem cells in ways that are bringing us closer to developing new treatments. Many potential treatments are currently being tested in animal models and some have already been brought to clinical trials. In February 2010 the British company ReNeuron announced it had been approved to conduct a Phase I clinical trial of a neural stem cell treatment for stroke. The first embryonic stem cell-based treatment for acute spinal cord injury is currently under review by the U.S. Food and Drug Administration (FDA) and will hopefully move into clinical trials soon. Although it is sometimes hard to see, stem cell science is moving forward. We are tremendously optimistic that stem cell therapies will someday be available to treat a wide range of human diseases and conditions.
There are different types of stem cells—each with their own purpose.
There are many different types of stem cells that come from different places in the body or are formed at different times in our lives. These include embryonic stem cells that exist only at the earliest stages of development and various types of ‘tissue-specific’ or ‘adult’ stem cells that appear during fetal development and remain in our bodies throughout life.
Our bodies use different types of tissue-specific stem cells to fit a particular purpose. Tissue-specific stem cells are limited in their potential and largely make the cell types found in the tissue from which they are derived. For example, the blood-forming stem cells (or hematopoietic stem cells) in the bone marrow regenerate the blood, while neural stem cells in the brain make brain cells. A neural stem cell won’t spontaneously make a blood cell and likewise a hematopoietic stem cell won’t spontaneously make a brain cell. Thus, it is unlikely that a single cell type could be used to treat a multitude of unrelated diseases that involve different tissues or organs. Be wary of clinics that offer treatments with stem cells that originate from a part of the body that is different from the part being treated.
2. A single stem cell treatment will not work on a multitude of unrelated diseases or conditions.
As described above, each type of stem cell fulfills a specific function in the body and cannot be expected to make cell types from other tissues. Thus, it is unlikely that a single type of stem cell treatment can treat multiple unrelated conditions, such as diabetes and Parkinson’s disease. The underlying causes are very different and different cell types would need to be replaced to treat each condition. It is critical that the cell type used as a treatment be appropriate to the specific disease or condition.
Embryonic stem cells may one day be used to generate treatments for a range of human diseases. However, embryonic stem cells themselves cannot directly be used for therapies as they would likely cause tumors and are unlikely to become the cells needed to regenerate a tissue on their own. They would first need to be coaxed to develop into specialized cell types before transplantation. A major warning sign that a clinic may not be credible is when treatments are offered for a wide variety of conditions but rely on a single cell type.
3. Currently, there are very few widely accepted stem cell therapies.
The range of diseases where stem cell treatments have been shown to be beneficial in responsibly conducted clinical trials is still extremely restricted. The best defined and most extensively used is blood stem cell transplantation to treat diseases and conditions of the blood and immune system, or to restore the blood system after treatments for specific cancers. Some bone, skin and corneal diseases or injuries can be treated with grafting of tissue that depends upon stem cells from these organs. These therapies are also generally accepted as safe and effective by the medical community.
4. Just because people say stem cells helped them doesn’t mean they did.
There are three main reasons why a person might feel better that are unrelated to the actual stem cell treatment: the ‘placebo effect’, accompanying treatments, and natural fluctuations of the disease or condition. The intense desire or belief that a treatment will work can cause a person to feel like it has and to even experience positive physical changes, such as improved movement or less pain. This phenomenon is called the placebo effect. Even having a positive conversation with a doctor can cause a person to feel improvement. Likewise, other techniques offered along with stem cell treatment—such as changes to diet, relaxation, physical therapy, medication, etc.—may make a person feel better in a way that is unrelated to the stem cells. Also, the severity of symptoms of many conditions can change over time, resulting in either temporary improvement or decline, which can complicate the interpretation of the effectiveness of treatments. These factors are so widespread that without testing in a controlled clinical study, where a group that receives a treatment is carefully compared against a group that does not receive this treatment, it is very difficult to determine the real effect of any therapy. Be wary of clinics that measure or advertise their results primarily through patient testimonials.
5. A large part of why it takes time to develop new therapies is that science itself is a long and difficult process.
Science, in general, is a long and involved process. Understanding what goes wrong in disease or injury and how to fix it takes time. New ideas have to be tested first in a research laboratory, and many times the new ideas don’t work. Even once the basic science has been established, translating it into an effective medical treatment is a long and difficult process. Something that looks promising in cultured cells may fail as a therapy in an animal model and something that works in an animal model may fail when it is tried on humans. Once therapies are tested in humans, ensuring patient safety becomes a critical issue and this means starting with very few people until the safety and side effects are better understood.
6. To be used in treatments, stem cells will have to be instructed to behave in specific ways.
Bone marrow transplantation is typically successful because we are asking the cells to do exactly what they were designed to do, make more blood. For other conditions, we may want the cells to behave in ways that are different from how they would ordinarily work in the body. One of the greatest barriers to the development of successful stem cell therapies is to get the cells to behave in the desired way. Also, once transplanted inside the body the cells need to integrate and function in concert with the body’s other cells. For example, to treat many neurological conditions the cells we implant will need to grow into specific types of neurons, and to work they will also have to know which other neurons to make connections with and how to make these connections. We are still learning about how to direct stem cells to become the right cell type, to grow only as much as we need them to, and the best ways to transplant them. Discovering how to do all this will take time. Be wary of claims that stem cells will somehow just know where to go and what to do to treat a specific condition.
7. Just because stem cells came from your body doesn’t mean they are safe.
Every medical procedure has risks. While you are unlikely to have an immune response to your own cells, the procedures used to acquire, grow and deliver them are potentially risky. As soon as the cells leave your body they may be subjected to a number of manipulations that could change the characteristics of the cells. If they are grown in culture (a process called expansion), the cells may lose the normal mechanisms that control growth or may lose the ability to specialize into the cell types you need. The cells may become contaminated with bacteria, viruses or other pathogens that could cause disease. The procedure to either remove or inject the cells also carries risk, from introducing an infection to damaging the tissue into which they are injected.
8. There is something to lose by trying an unproven treatment.
Some of the conditions that clinics claim are treatable with stem cells are considered incurable by other means. It is easy to understand why people might feel they have nothing to lose from trying something even if it is unproven. However, there are very real risks of developing complications, both immediate and long-term, while the chance of experiencing a benefit is likely very low. In one publicized case, a young boy developed brain tumors as a result of a stem cell treatment. Participating in an unproven treatment may make a person ineligible to participate in upcoming clinical trials (see also number 9). Where cost is high, there may be long-term financial implications for patients, their families and communities. If travel is involved there are additional considerations, not the least of which is being away from family and friends.
9. An experimental treatment offered for sale is not the same as a clinical trial.
The fact that a procedure is experimental does not automatically mean that it is part of a research study or clinical trial. A responsible clinical trial can be characterized by a number of key features. There is preclinical data supporting that the treatment being tested is likely to be safe and effective. Before starting, there is oversight by an independent group such as an Institutional Review Board or medical ethics committee that protect patients’ rights, and in many countries the trial is assessed and approved by a national regulatory agency, such as the European Medicines Agency (EMA) or the U.S. Food and Drug Administration (FDA). The study itself is designed to answer specific questions about a new treatment or a new way of using current treatments, often with a control group to which the group of people receiving the new treatment is compared. Typically, the cost of the new treatment and trial monitoring is defrayed by the company developing the treatment or by local or national government funding. Beware of expensive treatments that have not passed successfully through clinical trials.
Responsibly-conducted clinical trials are critical to the development of new treatments as they allow us to learn whether these treatments are safe and effective. The ISSCR supports participation in responsible clinical trials after careful consideration of the issues highlighted on this site and in discussion with a trusted physician.
10. Stem cell science is constantly moving forward.
Stem cell science is extraordinarily promising. There have been great advances in treating diseases and conditions of the blood system using blood-forming stem cells, and these show us just how powerful stem cell therapies can be. Scientists all over the world are researching ways to harness stem cells and use them to learn more about, to diagnose, and to treat various diseases and conditions. Every day scientists are working on new ways to shape and control different types of stem cells in ways that are bringing us closer to developing new treatments. Many potential treatments are currently being tested in animal models and some have already been brought to clinical trials. In February 2010 the British company ReNeuron announced it had been approved to conduct a Phase I clinical trial of a neural stem cell treatment for stroke. The first embryonic stem cell-based treatment for acute spinal cord injury is currently under review by the U.S. Food and Drug Administration (FDA) and will hopefully move into clinical trials soon. Although it is sometimes hard to see, stem cell science is moving forward. We are tremendously optimistic that stem cell therapies will someday be available to treat a wide range of human diseases and conditions.
Tuesday, June 22, 2010
Report: Spine Stimulation May Benefit Parkinson’s Disease Patients
By Steven Marsh
Patients who have been diagnosed with Parkinson’s disease (PD) may have relief from symptoms associated with the condition in the near future, according to a study presented at the 2010 American Society for Stereotactical and Functional Neurosurgery.
In an effort to find potential treatments for individuals with the nervous system disorder, a team of researchers at Rhode Island Hospital conducted a series of exercises that stimulated the spinal cord on an animal model, which showed signs of PD. Because the findings displayed better motor function in the animal, the investigators tested the treatment with spinal cord simulation on a male patient aged 82 years.
While the individual wasn’t receiving any form of medication as treatment for the disorder, researchers used different frequencies of stimulation to determine if a human would experience similar results compared to the animal model.
The researchers discovered that high stimulation frequencies made it easier for the patient to walk, while low frequencies worsened PD side effects.
While the results of the study did give investigators some insight as to how to treat PD patients, clinical trials with a larger group of patients would be more beneficial to developing treatment.
Finding therapies for this disorder is growing in interest throughout the medical world, as QR Pharma and Massachusetts General Hospital have launched research to determine a way to block a protein associated the development of PD.ADNFCR-1960-ID-19845071-ADNFCR
Patients who have been diagnosed with Parkinson’s disease (PD) may have relief from symptoms associated with the condition in the near future, according to a study presented at the 2010 American Society for Stereotactical and Functional Neurosurgery.
In an effort to find potential treatments for individuals with the nervous system disorder, a team of researchers at Rhode Island Hospital conducted a series of exercises that stimulated the spinal cord on an animal model, which showed signs of PD. Because the findings displayed better motor function in the animal, the investigators tested the treatment with spinal cord simulation on a male patient aged 82 years.
While the individual wasn’t receiving any form of medication as treatment for the disorder, researchers used different frequencies of stimulation to determine if a human would experience similar results compared to the animal model.
The researchers discovered that high stimulation frequencies made it easier for the patient to walk, while low frequencies worsened PD side effects.
While the results of the study did give investigators some insight as to how to treat PD patients, clinical trials with a larger group of patients would be more beneficial to developing treatment.
Finding therapies for this disorder is growing in interest throughout the medical world, as QR Pharma and Massachusetts General Hospital have launched research to determine a way to block a protein associated the development of PD.ADNFCR-1960-ID-19845071-ADNFCR
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)
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