Research - Stem Cells from Patient's Own Skin #


Procedure Could Help Local Patients Beat Parkinson's Disease

Copied from The Northwest Parkinson’s Foundation Weekly News Update

Chris Chan

NBC 7 San Diego - Researchers hope a procedure using patients' own stem cells will cure Parkinson's Disease, or at least eliminate symptoms for decades.

Eight patients have joined the project at Scripps Research Institute in La Jolla to take part in the initial trial. Before they are able to proceed, they must get funding and obtain approval from the Food and Drug Administration.

"We're all treading water until the funds can be found and the hoops that the FDA give us can be jumped through," said Cassandra Peters, who was a paralegal at a law firm until 2005, when the symptoms of Parkinson's made it too difficult to work. She was diagnosed at age 44, 13 years ago.

The planned procedure entails taking a skin sample from the patients, then creating pluripotent stem cells with the genetic material. Millions of stem cells will then be injected into the brain to create dopamine neurons, which are destroyed by Parkinson's disease.

It's a technique discovered by Japanese researcher Shinya Yamanaka who won the Nobel Prize in Medicine in 2012.
Jeanne Loring, Ph.D., Director of the Center of Stem Cell Research at the Scripps Research Institute said similar work has been done in the past.

"There was work done in the 1980s and early 1990s in which fetal tissue was transplanted into the brains of people with Parkinson's disease," Loring said.

She said the problem was that fetal tissue produced inconsistent results.Loring believes using pluripotent stem cells derived from the same patient in which the cells will be transplanted will be much more reliable.

"The thing about Parkinson's Disease is there's really only one nerve cell type that needs to be replaced, and we know exactly where to put it," Loring said.

That confidence has been passed to the patients in this project who, unlike many other research projects, have been very involved in the process-- meeting with scientists and researchers in the laboratory.

"If this procedure works, and I know that it will, it will be the answer to so many people's prayers," Peters said.

Funding for the procedure remains a challenge as the government has not provided any grants for the project. Patients have been taking matters into their own hands, raising money for the non-profit Summit 4 Stem Cell, which hopes that Parkinson's victims' hike to Mount Everest base camp can help raise money for this initial procedure.

Edward Fitzpatrick, who was diagnosed with Parkinson's nearly seven years ago, said the group has raised nearly one million dollars and needs to raise $1.5 million more to perform the procedure on the initial test group.

The Food and Drug Administration must also give its approval. Dr. Loring said there were no set requirements from the regulatory group, but researchers are working closely with the FDA to reach a solution.


Treatment - Sunlight #


‘Sunlight’ found to lower blood pressure

By Dr John Briffa on 8 May 2013 in Sunlight

There’s abundant evidence linking sunlight exposure with a reduced risk of chronic diseases including heart disease, several forms of cancer, multiple sclerosis and diabetes. If the sun is bright enough and high enough in the sky, sunlight can stimulate the product of vitamin D (actually, a hormone) in the skin. Higher levels of vitamin D in the body are also associated with a reduced risk of chronic disease. This supports the idea that sunlight’s apparent benefits are mediated through the production of vitamin D.

However, the nature of such so-called ‘epidemiological’ evidence proves little. All it tells us is that both higher levels of sunlight exposure and higher levels of vitamin D are associated with better health. None of this actually tells us whether sunlight is beneficial to health and even if it is, that these benefits are brought through higher levels of vitamin D.

However, it’s perhaps worth considering the fact that vitamin D receptors exist widely around the body including fat tissue, the adrenal gland, bone, brain, breast, cartilage, colon, hair follicles, intestine, skeletal muscle (muscles connected to bones such as those in the legs and arms), cardiac (heart) muscle, kidney, liver, ovary, pituitary gland, retina, sperm, thyroid and uterus (womb). The presence of a receptor for a substance can be taken as a sign that this substance exerts some influence over the structure and/or function of that tissue.

Another piece of evidence which points to a direct effect of vitamin D on health is the fact that vitamin D has been found to have the capacity to bind to about 3,000 sites within DNA [1]. This research also found that vitamin D could affect the activity of 229 genes, including several the influence conditions that are linked to vitamin D.

However even if vitamin D directly affects health, this does not mean that the benefits attributed to sunlight are necessarily only related to its ability to boost vitamin D levels. We know, for instance, that light exposure can have a profound influence on mood and sleep during months when no vitamin D will be made in the skin at all.

Also, in an animal model, light exposure has be found to help multiple sclerosis and that this benefit could not really be explained by changes in vitamin D levels. .

I was interested to read about a piece of research announced today in which the impact of light and vitamin D on blood pressure was assessed. You can read a report of this research here.

This research, conducted in Edinburgh, UK, involved exposing individuals to a 20-minute session under lamps that gave off ultraviolet light as well as heat. The impact on blood pressure was compared to another session in which the individuals were exposed to similar lamps that gave off heat but no UV light.

According to the report, the UV light exposure led to a significant reduction in blood pressure compared to exposure to heat alone. And, it seems, there was no appreciable change in vitamin D that might explain the difference in effects. The benefits appear to have been put down to an increased production of nitric oxide, which has blood vessel relaxant and blood pressure lowering effects.

Without access to the actual paper (due to be presented at a scientific meeting on Friday) it’s difficult to say much more about this research. But it adds to the idea that the benefits of sunlight are likely to come from mechanisms that go beyond vitamin D. Also, it was interesting to note recognition from the authors of this study that whatever impact sunlight has on skin cancer risk needs to be balanced with whatever benefits may be had in terms of improved cardiovascular health. And that’s before we begin to consider any other benefits sunlight has in terms of chronic diseases such as cancer, diabetes and multiple sclerosis.


1. Ramagopalan SV, et al. A ChIP-seq defined genome-wide map of vitamin D receptor binding: Associations with disease and evolution. Genome Res. 2010 Aug 24. [Epub ahead of print]


Treatment - Psychiatric Treatment Crucial for Many Pd Patients


Psychiatric Treatment Crucial for Many Parkinson’s Patients

Copied from Northwest Parkinson’s Foundation Weekly News Update

Joan Arehart-Treichel

Psychiatric News - A decade or so ago, psychiatrists would have been hard pressed to provide evidence-based psychiatric treatments to Parkinson’s patients. Thanks to research advances, that situation has improved considerably.

Not just the public, but many clinicians, believe that Parkinson’s disease is exclusively a neurological disorder—that is, that it only entails tremors, stiffness, and difficulty with balance.

Yet there are many psychiatric aspects to the illness as well, psychiatrists who specialize in Parkinson’s disease stressed during recent interviews with Psychiatric News.

Parkinson’s patients can experience a raft of psychiatric symptoms, Daniel Weintraub, M.D., an associate professor of psychiatry and neurology at the University of Pennsylvania and a psychiatrist with the Parkinson’s Disease Research, Education, and Clinical Center at the Philadelphia Veterans Affairs Medical Center, reported. These symptoms include anxiety, depression, personality changes, memory problems, sleep problems, impulse control difficulties, psychosis, and dementia.

And these symptoms can occur at different stages of the disease and have different causes, Parkinson’s researcher Laura Marsh, M.D., pointed out. She is a professor of psychiatry and neurology at Baylor College of Medicine and director of the Mental Health Care Line at the Michael E. DeBakey Veterans Affairs Medical Center.

Among individuals with Parkinson’s, anxiety disorders develop at a higher rate than in the general population, Marsh indicated, and can have their onset up to 20 years or so before tremors and other motor aspects of the disease are apparent. Also, several studies show a high rate of a family history of anxiety conditions in such individuals. Thus it looks as if there could be genetic links between anxiety and Parkinson’s in some individuals.

As for depressive symptoms, they can also occur before the motor symptoms of Parkinson’s surface, Marsh noted, but closer than anxiety symptoms to the time that the motor symptoms appear. “I have seen a number of patients who had never had a mood disorder earlier in their life, but who developed a depressive disorder around age 55, followed by the motor symptoms of Parkinson’s three years later,” she said. And here too, it looks as if the depression may be an early sign of the parkinsonian disease process, not a reaction to the motor symptoms of the disease.

According to psychiatrist and Parkinson’s expert Laura Marsh, M.D., even though Parkinson’s is a chronic, progressive disease with no cure, actor Michael J. Fox is an example of how people with it can still live rich lives.

Indeed, “patients with depression will often say, ‘Why wouldn’t I be depressed? I have Parkinson’s,’ when in fact disability due to Parkinson’s motor symptoms is not correlated with depressive symptoms,” William McDonald, M.D., a professor of psychiatry at Emory University and a Parkinson’s researcher, told Psychiatric News. “Clinically we have found that some of the most disabled Parkinson’s patients are not depressed, and some of the most depressed Parkinson’s patients have only minor motor disabilities.”

The reason that anxiety and depression may be precursors of the appearance of Parkinson’s motor symptoms, Marsh suggested, may be due to the discovery, a few years ago, that the parkinsonian disease process starts in the brainstem and then advances to the midbrain. The brainstem contains serotonin and adrenergic neurons that could contribute to anxiety and depression, whereas the midbrain contains dopaminergic neurons that contribute to the motor symptoms of Parkinson’s, she explained.

The pathological gambling or hypersexuality that some Parkinson’s patients experience appears to be due, however, largely to the dopaminergic medications that patients are prescribed for their motor symptoms—not to the disease process itself, Marsh noted.

And the same is true for the hallucinations or delusions that some Parkinson’s patients experience, Weintraub added. However, as Marsh noted, “the evidence suggests that they are due not just to dopaminergic medications, but also to the disease process.”

Since psychiatric problems can be a significant part of Parkinson’s disease, what can psychiatrists do to help Parkinson’s patients? “Until relatively recently I couldn’t have answered this question very definitively,” Matthew Menza, M.D., chair of psychiatry at the Robert Wood Johnson Medical School and a Parkinson’s expert, said during an interview. “But I think that over the past decade, there have been a number of reasonably good studies that have begun to address the question.”

Regarding anxiety, for example, “One of the more interesting things that has been demonstrated recently is that exercise, which is a well-validated treatment for anxiety disorders in general, also appears to benefit Parkinson’s patients who are anxious,” Menza said.

Several randomized, double-blind, placebo-controlled trials have shown that antidepressants can help Parkinson’s patients who are depressed, Menza also pointed out. One of these was conducted by McDonald and his colleagues and is in press with Neurology. The trial has demonstrated that “Parkinson’s depression is very treatable using standard antidepressants and [these medications] can be remarkably effective in improving quality of life and even motor symptoms, with few adverse effects,” McDonald said.

Cognitive-behavioral therapy (CBT) can also benefit depressed Parkinson’s patients, Roseanne Dobkin, Ph.D., along with Menza and other colleagues at the Robert Wood Johnson Medical School, reported in the October 2011 American Journal of Psychiatry. Eighty depressed Parkinson’s subjects participated in a randomized controlled trial in which CBT was compared with clinical monitoring. CBT was modified to meet unique needs of the Parkinson’s population and was provided for 10 weeks. Assessments were completed by blind raters at baseline, midway through treatment, at the end of treatment, and finally four weeks later. The CBT group experienced significantly less depression by the end of treatment than the control group did, and these gains were maintained four weeks later.

Most people with Parkinson’s have some sleep problems. “It looks as if many of the drugs that we psychiatrists use for sleep disorders probably have some [positive] effect in people with Parkinson’s disease,” Menza observed.

Regarding the memory problems that are common later in Parkinson’s disease, the drugs available to treat Alzheimer’s disease “can help a bit,” he said.

“So psychiatrists, I think, have available to them a variety of medications and nonmedication therapies that may be useful for people with Parkinson’s,” he noted.

And still more psychiatric tools to help Parkinson’s patients may be emerging in the near future, Marsh indicated. For example, when most antipsychotic medications are given to Parkinson’s patients for hallucinations or delusions, the antipsychotics may eliminate the symptoms, but they may also block the action of the dopaminergic drugs given to control motor symptoms. As a result, the patients’ motor symptoms can get worse. New antipsychotics in the development pipeline might be able to treat psychotic symptoms successfully without increasing the patients’ motor symptoms.

“One of the great things about taking care of individuals with Parkinson’s disease, of all the neurodegenerative disorders, is that it has very effective treatments,” Marsh declared. “So even though it is a chronic, progressive, neurodegenerative disease, and even though it has no cure, people can live with it and do well despite its challenges, especially if the psychiatric problems are treated.”

How Many Psychiatrists See Parkinson’s Patients?

Not that many, Laura Marsh, M.D., a professor of psychiatry and neurology at Baylor College of Medicine and a Parkinson’s researcher, told Psychiatric News. “And when they do, it is often because the problems have gotten out of hand—say, someone is really depressed or suicidal.”

And do neurologists ever seek out psychiatrists to help them with Parkinson’s patients’ psychiatric problems? “It really depends,” said Daniel Weintraub, M.D., an associate professor of psychiatry and neurology at the University of Pennsylvania. “If you are in a place such as I am, which is a large academic medical center, I do work closely with neurologists…. At other places where there may not be the same access to psychiatrists, where Parkinson’s care may not even be provided by movement-disorders neurologists but by a general neurologist, then I think that the collaboration is less likely to exist.”

Thus “in Parkinson’s disease, the psychiatric complications remain underrecognized or undertreated,” Marsh asserted.
So how might psychiatrists reach out to help Parkinson’s patients?

One way is to become involved in interdisciplinary care teams and learn about the motor and other somatic and cognitive features of the disease, Marsh suggested. “It is a rewarding condition to treat psychiatrically because treatment works.”

Also, psychiatrists should stay alert for Parkinson’s in older adults who are depressed, George Grossberg, M.D., a professor of psychiatry and neurology at St. Louis University and a geriatric psychiatrist with an interest in Parkinson’s, advised during an interview. “Often we psychiatrists may be the first ones to suspect Parkinson’s in such patients,” he said.

Moreover, psychiatrists who consult to assisted-living facilities or nursing homes should be especially vigilant for Parkinson’s disease in patients, Grossberg said, since neurologists who specialize in Parkinson’s rarely provide such consultation.

Search Is On for New Treatments

“There is an energetic effort right now to find treatments that slow the progression of Parkinson’s,” Matthew Menza, M.D., chair of psychiatry at the Robert Wood Johnson Medical School and a Parkinson’s expert, said during an interview. The effort is focused on neuroprotective treatments such as nonsteroidal inflammatory drugs, since there is substantial evidence that inflammation is involved in the Parkinson’s disease process.

“Many of the disorders that we deal with in psychiatry start early in life—in childhood or adolescence—and some of them appear to get worse over the years,” he said. “So if we had a treatment that was neuroprotective, it might have application in psychiatric disorders. True, nothing is ready for prime time right now. But it is certainly something that people are thinking about.”

“Parkinson’s disease is in many ways the prototypical neuropsychiatric disorder in that it causes clear damage to the brain, but also has many psychiatric aspects to it,” Menza observed. “The hope of those of us who work in this interface between psychiatry and neurology is that if we understand more about Parkinson’s, it’s going to lead to a better understanding of many other diseases that we believe are based in the brain, such as attention-deficit/hyperactivity disorder, bipolar depression, and schizophrenia….[And] if we understood Parkinson’s better, we might have better insights into how to treat these other purely psychiatric disorders.


Treatment - Lee Silverman Voice Treatment


Parkinson’s patients live large in a new program

Copied from The Northwest Parkinson’s Foundation Weekly News Update

Dierdre Cox Baker

quad-city - The ravages of Parkinson’s disease are described as making a person seem smaller.

The individual, probably an older man, grows hunched, speaks softly, and has difficulty walking and doing regular daily activities.

Identified in 1817 by British Dr. James Parkinson, the disorder has been studied for almost two full centuries. However, new therapies have been introduced because it is one of the most common neurological conditions in aging adults.

Parkinson’s is confirmed in about 1 million people each year, and the majority of them are male. The cause has been traced to low levels of the organic chemical dopamine in the brain, but it is not fully understood. There is no cure, and most patients are diagnosed after they turn 50 years old.

All of these realities help explain the excitement of Genesis Medical Center therapists involved in the LSVT outpatient program, which stands for Lee Silverman Voice Treatment. There are voice, occupational and physical therapists involved in the program, originally developed during the 1980s and named after an Arizona woman.

Genesis offers two aspects of LSVT: One is called “Loud” for the voice therapy aspect and one is called “Big” for the physical therapy.

A highly successful program

“With Parkinson’s disease, the people start to get small,” explained Barb Vanderlinden, a speech therapist. She then drew a picture of how the disease affects an individual. “Their speech gets small, they hunch over and look small, and they walk small. Every motion is decreased.”

Physical therapist Pat Glasgow agreed. “Often, as they become smaller and smaller, they still see themselves as normal. And what looks normal to us looks to them as huge,” she said.

The LSVT therapists try to teach — and preach — the concept of living big. They aim for patients to feel that “big” is a new normal level of life.

A month-long series of repeated exercises has paid off with visible success for every patient in the program, the four therapists agreed.

“I’ve never, ever really seen this program not work,” Glasgow said. “That’s exciting to me. We, and patients and their families, see improvements. It ranges from fairly good to dramatic changes in mobility.”

Dr. Ergun Uc, a neurologist, warns that treatments such as LSVT generally require a strong commitment, and compliance, from patients and caregivers and may not suit all who have Parkinson's disease. "For example, those would be the frail patients and those who have dementia," he said. Uc is a specialist in Parkinson's disease at the University of Iowa .He also works at the Veterans Administration Medical Center in Iowa City.

Patient says it works, too

As a young man, Ed Stolley of Bettendorf fought in the Vietnam War and was exposed to Agent Orange, a herbicide used to clear foliage in the jungles of Vietnam and later linked to several health issues in veterans of the Asian war. Stolley, 69, explained that his exposure led to a Parkinson’s disease diagnosis six years ago.

“It affects me quite a bit,” he said. For one thing, family members and friends have noticed that he speaks too softly.

But Stolley’s daughter is a nurse who learned about the LSVT program at Genesis and urged him to get involved.

He found it difficult to complete the therapy exercises, but he’s very thankful that he did. Stolley participated in two types of therapy at the same time, working on both on his voice and his movement. The regimen was complicated by recovery from a ruptured appendix and the mix of prescription medicines that he takes.

“I didn’t think I could make it. It can be a difficult program,” he said.

Improved approach from past

Past therapies for Parkinson’s were to treat patients where there were deficits, said Mickey Owens, an occupational therapist with the LSVT program. “It was kind of like one and done,” she added.

Owens works with patients on their daily activities such as bathing, dressing and living in the home.

The program has specific protocols and exercises, and it’s a lifelong process, said Susan Bode, a physical therapist.

“It’s unique because of the intensity and frequency. Both are modeled to change the movement patterns,” she said.

The therapists agreed that traditional programs ended in less-successful recovery rates. That led to their professional frustration and is why they sought out a programming change.

“We’ve had great success with this,” Bode said.

Stolley, the Parkinson’s patient, agreed.

“I’m glad I stuck it out. It was the best thing I’ve done,” he said, adding, “I would recommend this program to any person with Parkinson’s. I’m that happy about it.”

Treatment - Acupuncture


Acupuncture Slows Parkinson’s Disease - New Discovery

Copied from The Northwest Parkinson’s Foundation Weekly News Update - New research reveals how acupuncture protects the brain in areas damaged by Parkinson’s disease. Scientists at the World Health Organization Collaborating Center for Traditional Medicine have discovered two acupuncture points that prevent the breakdown of an important brain protecting enzyme, tyrosine hydroxylase. This enzyme helps the body to create L-DOPA, an important dopamine precursor and drug used in the treatment of Parkinson’s disease. It is now known that acupuncture prevents decreases of the L-DOPA creating enzyme in the thalamic portions of the brain thereby improving the motor function that is destroyed by Parkinson’s disease.

Loss of dopamine neurons in the substantia nigra portion of the brain is a key pathology in Parkinson’s disease and tardive dyskinesia. The World Health Organization (WHO) scientists have discovered that acupuncture inhibits decreases of tyrosine hydroxylase in nigrostriatal dopaminergic neurons thereby protecting dopamine neuron levels in the substantia nigra portion of the brain. Depletion of these neurons leads to Parkinson’s disease and acupuncture stimulation of acupoints GB34 and LV3 prevents depletion by sustaining tyrosine hydroxylase levels.

About the Acupoints
Acupuncture point LV3 has been historically used to treat tremors such as those associated with Parkinson’s disease. It is located on the dorsum of the foot in the fossa between the first and second metatarsal bones. Its traditional classifications in Chinese medicine theory include: shu-stream point, source point, earth point, heavenly star point. Traditional functions of the point include: move Liver Qi, quell Liver Yang and wind, nourish the Liver, regulate menstruation, stop pain and clear the head and eyes. Common applications for the use of LV3 (Great Rushing, Taichong) include the treatment of menstrual disorders, headaches, dizziness, epilepsy, tremors, high blood pressure, insomnia and blurry vision.

Acupuncture point GB34 has been historically used to treat a variety of conditions including hemiplegia, total paralysis of the arm, leg and trunk on one side of the body. Common usage by licensed acupuncturists includes the treatment of tendon, ligament and joint disorders. Traditional classifications for this acupoint are: He-Sea, earth point, influential point of the tendons, heavenly star point. GB34 is indicated for the treatment of pain related conditions such as sciatica, hip pain, joint pain, muscle pain, tendon pain and knee pain.

According to Chinese medicine theory, both acupuncture points harmonize the Shaoyang channel. This makes both points well suited to treat disorders associated with tremors and other symptoms associated with Parkinson’s disease. Further research is required to determine whether or not other acupoints that harmonize the Shaoyang channel prevent decreases of tyrosine hydroxylase in the brain.

Treatment - Telemedicine, Virtual House Calls


Virtual’ House Calls for Parkinson’s Patients Effective

Copied from The Northwest Parkinson’s Foundation Weekly Newsletter - A study out today in the journal JAMA Neurology shows that telemedicine check-ups for people with Parkinson’s disease can not only provide effective care but also generate a significant economic benefit. These ‘virtual’ visits with physicians – in which the patient participates from the comfort of their own home – demonstrate that quality specialized care can be effectively delivered to individuals in remote locations.

“This study shows that providing specialty care to people with Parkinson’s disease directly into their homes is feasible, saves patients substantial time and travel, and may offer comparable clinical benefits to in-person care,” said University of Rochester Medical Center neurologist Kevin Biglan, M.D., M.P.H., the senior author of the study.

One of the major challenges in providing care to Parkinson’s patients is geography. The multifaceted nature of the disease with its complex combination of behavioral, cognitive, and physical symptoms often demands that patients receive care from a physician who focuses on treating neurological disorders. In fact, studies have shown that access to specialized neurological care improves outcomes. For example, Medicare beneficiaries with Parkinson’s who do NOT see a neurologist are 14 percent more likely to fracture a hip, 21 percent more likely to be placed in a nursing home, and 22 percent more likely to die. Parkinson’s patients who see a neurologist are also three times more likely to be satisfied with their care.

However, specialists who treat movement disorders such as Parkinson’s tend to be found at larger medical centers. Individuals with the disease who live in rural or underserved areas are less likely to have access to a neurologist nearby. Furthermore, the nature of the disease – particularly the impact on muscle control and coordination – can make it difficult to travel long distances to see a specialist.

The study recruited 20 patients from upstate New York and Maryland who were seen by Biglan and E. Ray Dorsey, M.D., M.B.A. with Johns Hopkins University, respectively. Over the next seven months, half of the patients received in-person care, meaning they visited the doctor’s office for their check-ups. The other half of the participants received care in their homes using a secure internet video technology akin to Skype.

While video-based evaluations can have limitations, the researchers have found that Parkinson’s disease is an ideal candidate for telemedicine. “Parkinson’s is a very visual disease,” said Biglan. “You don’t necessarily have to physically touch patients to understand how they are doing.”

At the end of the seven months, the researchers measured the patients' perception of their quality of life and the level of care they were receiving. They found that the patients who received virtual house calls did as well as those who received in-person care.

The researchers also measure the economic value of allowing individuals to receive care in their own homes. They found that the average telemedicine visit lasted 53 minutes from beginning to end. In contrast, patients who received in-person care spent an average of 255 minutes per visit when factoring in the trip to and from the doctor’s office for a total of 100 miles and 3 hours of travel time over the seven months duration of the study.

While the study demonstrates the potential of providing care to remote patients with chronic conditions such as Parkinson’s, the researchers point out that barriers to the widespread adoption of this model exist. Specifically, licensing and reimbursement requirements make it difficult – if not impossible – to provide care across state lines and for physicians to be reimbursed for telemedicine-based care provided to patients in their homes.

“While policy changes will be necessary to fully implement this model of care, this study shows that quality in-home care is feasible,” said Biglan.

Additional co-authors include Matthew Grana, Micheal Bull, Benjamin George, Christopher Beck, Balaraman Rajan, and Abraham Seidmann with the University of Rochester, and Vinayak Venkataraman and Cynthia Boyd with Johns Hopkins University. The study was supported by grants from Google and Excellus BlueCross BlueShield.

Treatment - MEG Scan


Rare Glimpse Into Parkinson’s Disease Using Neuroimaging Technology


Copied from The Northwest Parkinson’s Foundation Weekly News Update

Staff Editor - A University of Nebraska Medical Center research team has found a way to monitor brain injuries that occur in Parkinson's disease providing clinicians a rare glimpse into the disease process.

By using magnetoencephalography (MEG) imaging Tony Wilson, Ph.D., an assistant professor in the UNMC Department of Pharmacology and Experimental Neuroscience and lead study investigator, was able to pinpoint the regions of the brain affected by this debilitating disease.

The results of Dr. Wilson's research were published in the Journal Cerebral Cortex, one of the top ranked neuroscience journals.

In the year-long study, Dr. Wilson and colleagues scanned the brains of 19 patients with Parkinson's and 16 without to see how different regions of the brain were involved in the initiation of basic movements.

Using MEG imaging, the investigative team identified the regions of the brain that became engaged when the person performed a simple hand movement.

"The scans revealed that patients with Parkinson's disease had clear deficits in critical brain centers during the movements," Dr. Wilson said.

Now that the specific regions of the brain affected by Parkinson's have been identified, the next step is to develop medications designed to slow the disease's progression.

"Up to this point, we have not had a foolproof way of diagnosing or monitoring Parkinson's. The hope is that this will become a biomarker that will aid clinicians in determining the best therapeutic methods to use for their patients," he said.

"This research provides an exciting new avenue for translational research," said Howard Gendelman, M.D., chairman of the UNMC Department of Pharmacology and Experimental Neuroscience and co-investigator on the study.

Gendelman and his team have, for more than 12 years, worked to not only understand Parkinson's disease progression but also to slow it through immune therapy. The work would not have been possible without a vigorous collaboration between neurologists, statisticians, psychologists and neuroscientists.

"Nebraska is perhaps one of the few research centers worldwide that boasts of so many people with divergent interests able to work together so effectively," Dr. Gendelman said.

He said this new technique will aid his research team's work into a novel therapy that has been proven in mouse models to reverse the neurodegenerative effects of the disease by changing the body's immune response.

"The technique offers opportunities to accurately diagnose the disease and gauge its progression in ways that are not possible with the standard neurological exam performed in the clinic," he said.

No other test provides that kind of accuracy with the relative ease and safety that this one does, said R. Lee Mosley, Ph.D., a study collaborator and associate professor in the PEN department adding that UNMC is one of a few places in the United States that has a MEG system.

Parkinson's disease is caused by the loss of neurons that produce dopamine, a nerve signaling chemical that controls movement and balance. Dr. Gendelman said the diagnosis and treatment of Parkinson's disease is of critical importance, not just nationwide, but in Nebraska where the incidence is so high.

The Parkinson's Disease Foundation estimates that about 1 million people in the United States and more than 4 million people worldwide have the disease. The incidence rate of Parkinson's disease is higher in Nebraska than in any other state in the country.

"Dr. Wilson has become an indispensible part of the research team providing new and important ways to better diagnosis this disease in a way that ensures patients are not harmed in any way, while still showing that they are responding appropriately to therapy," Dr. Gendelman said.

The participating authors of this study included: Elizabeth Heinrichs-Graham, a Ph.D. trainee and student inthe neuroscience and behavior program at the University of Nebraska at Omaha; UNMC neurologists, Pamela Santamaria, M.D., and Diego Torres-Russotto, M.D.; and UNMC statistician Jane Meza, Ph.D.

Treatment - Leukemia Drug May Benefit PD


Leukemia drug may benefit, Parkinson’s, Alzheimer’s disease patients


Copied from The Northwest Parkinson’s Foundation Weekly News Update



Robin Wulffson, MD - A drug that is currently used to treat leukemia has been found to slow the production of toxic proteins in the brain. These proteins have been linked to Parkinson’s disease, Alzheimer’s disease, and other forms of dementia. Researchers affiliated with Georgetown University in Washington, DC published their findings on May 10 in the journal Human Molecular Genetics.

The investigators treated mice with small doses of the drug nilotinib, which is used to treat chronic myelogenous leukemia; they found that it eliminated abnormal protein build-up in their brains. They focused on the alpha-Synuclein and tau proteins, which have been implicated in the development of Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Huntington’s disease, Lewy body dementia, and other neurodegenerative conditions. In these diseases, these proteins accumulate in brain cells and destroy them. Nilitonib works by removing these toxic proteins from brain cells.

When they began their research, the investigators were not sure whether nilitonib could cross the blood-brain barrier. The blood–brain barrier is a separation of circulating blood from the brain extracellular fluid in the brain and spinal cord. It restricts the passage of microscopic objects such as bacteria and large molecules, while allowing the passage of small molecules such as oxygen and carbon dioxide as well as hormones and glucose. However, they found that it could pass this barrier; thus, the same form of the drug used to treat leukemia patients could be used to treat patients with neurodegenerative diseases. The only difference was that they used much lower doses of nilotinib than the amount used to treat leukemia. They estimated that humans would only need 1% of the dose typically used in chemotherapy to see neurological benefits. This finding is likely to decrease the already minimal side-effects of nilotinib, such as dizziness.

Mice treated with nilotinib experienced an improvement in cognitive (thinking) and motor functions (muscle control). In addition, they also lived longer compared to mice treated with a placebo. Thus, the investigators are optimistic that the drug will quickly enter phase two clinical trials, provided they are able to secure funding. They note that the drug is also FDA-approved to treat leukemia; it is well tolerated in humans and toxicity studies have been done. This situation is likely to speed up the approval process.

The researchers are particularly anxious to use nilotinib to treat Lewy body dementia, which is a condition in which patients develop Alzheimer’s and Parkinson’s simultaneously. Currently, there is no treatment for the disorder. Although exploring this drug as a treatment for Lewy body dementia will be the researcher’s main priority going into clinical trials, they hope to expand to clinical trials on Parkinson’s and Alzheimer’s patients as well.

Treatment - New Way to Get Medication directly Into The Brain


Medical researchers close in on new pathway into brain


Copied from The Northwest Parkinson’s Foundation Weekly News Update



Daniel Chang

The Miami Herald - Stumped for years by a natural filter in the body that allows few substances, including lifesaving drugs, to enter the brain through the bloodstream, physicians who treat neurological diseases may soon have a new pathway to the organ via a technique developed by a physicist and an immunologist working together at Florida International University’s Herbert Wertheim College of Medicine.

The FIU researchers developed the technique to deliver and fully release the anti-HIV drug AZTTP into the brain, but their finding has the potential to also help patients who suffer from neurological diseases such as Alzheimer’s, Parkinson’s and epilepsy, as well as cancer.

“Anything where you have trouble getting drugs to the brain and releasing it, this opens so many opportunities,” said Madhavan Nair, an FIU professor and chair of the medical school’s immunology department.

In an in-vitro laboratory test with HIV-infected cells, Nair and a colleague, Sakhrat Khizroev, a professor of immunology and electrical engineering, attached the antiretroviral drug AZTTP to tiny, magneto-electric nanoparticles. Then, using magnetic energy, they guided the drug across a cell membrane created in the lab to mimic the blood-brain barrier found in the human body.

Once the drug reached its target, researchers triggered its release from the nanoparticle by zapping it with a low-energy electrical current. The drug remained functional and structurally sound after the release, according to the experiment findings.

“We learned to control electrical forces in the brain using magnetics,” said Khizroev, who designed, oversaw and supervised the entire project. “We pretty much opened a pathway to the brain.”

The test findings were published in April in the online peer-reviewed journal Nature Communications. Researchers believe that using this method will allow physicians to send a higher level of AZTTP — up to 97 percent more — to HIV-infected cells in the brain.

Currently, more than 99 percent of the antiretroviral therapies used to treat HIV (human immunodeficiency virus), such as AZTTP, are deposited in the liver, lungs and other organs before they reach the brain.

While anti-viral drugs have helped HIV patients live longer by reducing their viral loads, the drugs cannot pass the blood-brain barrier in significant amounts, which allows the virus to lurk unchecked in the brain and can lead to neurological damage, said Dr. Cheryl Holder, a practicing physician and FIU professor who specializes in treating patients with HIV.

“We know that even though the viral load is undetectable in the blood, we don’t know what’s going on in the brain fully,” Holder said.

HIV causes constant inflammation, she said, and the virus can pool in areas of the brain where medicine cannot reach, potentially causing damage.

“It’s important to get the drug to the brain,” she said, “to help prevent dementia in older patients, and inflammation.”

But the ability to target drug delivery and release it on demand in the brain has been impossible without opening the skull, Nair and Khizroev said.

Nair, an immunologist who specializes in HIV research, and Khizroev, an electrical engineer and physicist, began collaborating on the project about 18 months ago after winning a National Institutes of Health grant to study the use of magnetic particles.

One of the keys to success was controlling the release of the drug without adversely affecting the brain.

The researchers found their solution in the magneto-electric nanoparticles, which are uniquely suited to deliver and release drugs in the brain, Khizroev said. These nanoparticles can convert magnetic energy into the electrical energy needed to release the drugs without creating heat, which could potentially harm the brain.

The development of a new, less-invasive pathway to the brain would open the door to many new medical uses.

Khizroev said he recently returned from a trip to the University of Southern California, where he briefed physicians at the medical school on the technique and its potential for cancer treatment. And Nair said he received a letter recently on behalf of a 91-year-old man suffering from Parkinson’s, asking when the technique might become available for use in people.

That may take a while. With the first phase of testing successfully completed using in-vitro experiments, the second will take place at Emory University in Georgia, where researchers will test the technique on monkeys infected with HIV.

If researchers complete the second phase successfully, clinical trials on humans could follow, Nair said. Approval from the Food and Drug Administration would be required before the technique becomes commercially available, he said.

FIU researchers have applied for a patent and would receive royalties, they said, though the university would benefit the most, in part because a successful research project could open opportunities for more grant funding on other topics.

For Khizroev, who had previously done research on quantum computing and information processing, the project has offered a way to put his scientific knowledge to use in a way that could have a direct affect on people’s health.

“I wanted to apply my knowledge of nanoparticles to something important,” he said.

Treatment - Tai Chi Helps Balance in PD


AAN: Tai Chi Helps Balance in Parkinson's

Copied from The Northwest Parkinson’s Foundation Weekly News Update


Cole Petrochko, - Parkinson's disease patients who practiced tai chi had larger limits of stability and better sensory organization scores than those in a control group, researchers reported here.

Tai chi training was significantly associated with improvements in scores on the Sensory Organization Test from baseline (mean change 7.28, 95% CI 5.75 to 8.80, P<0.001), according to Fuzhong Li, PhD, of Oregon Research Institute in Eugene, and colleagues.

And, compared with patients who were taught only stretching exercises, those who had tai chi training had significantly improved limits of stability from baseline (mean change 9.41, 95% CI 6.75 to 10.74), Li noted during a poster session at the meeting of the American Academy of Neurology.

"Tai chi originated as a martial art, but it's very focused on being centered," Li told MedPage Today. A slow, meditative, physical practice, tai chi requires participants to extend and reach from their center of gravity, and then return to that center.

Previous studies have shown a correlation between tai chi participation and improved sensory organization, but these studies have not looked at how the "training results in positive change in sensory integration of balance responses," according to the authors.

The study measured the sensory integration of balance responses and changes in limits of stability after a tai chi training intervention in a sample of 130 mild-to-moderate Parkinson's disease patients. Participants had a mean age of 69 and had a disease stage of 1 to 4 on the Hoehn and Yahr staging scale.

Patients were evenly randomized to a tai chi training intervention or a stretching exercise control group, which each met twice a week for 24 weeks.

Outcomes of the study included scoring on the Sensory Organization Test, which tested participants in a variety of conditions such as with eyes closed. Participants' limits of stability included posture excursions in eight directions. Measures for these outcomes were taken at baseline and at 3 months and 6 months.

In addition to the significant changes in sensory organization and improvements to limits of stability, Li also noted that participants in the tai chi training saw modest gains in lower-body strength, although he did not report figures for this outcome.

Li noted that retention of participants in the tai chi intervention was high -- roughly 85% -- at 6 months. He added that the intervention improved outcomes at low cost, requiring no equipment and with minimal supervision.

He also noted that future research should use a larger patient population, measure fall risk and prevention, and include measures of patient-oriented outcomes.

Limitations of the study included the small size sample and the lack of specific measures for patients when they were on or off their medications.


Treatment - Peptides


Peptides helping researchers in search for Parkinson's disease treatment

Copied from The Northwest Parkinson’s Foundation Weekly News Update


Australian researchers have taken the first step in using bioactive peptides as the building blocks to help 'build a new brain' to treat degenerative brain disease. - Deakin University biomedical scientist Dr Richard Williams is working in a team with Dr David Nisbet from the Australian National University and Dr Clare Parish at the Florey Neuroscience Institute to develop a way to repair the damaged parts of the brain that cause Parkinson's disease.

Parkinson's disease develops when the brain cells (or neurons) that produce the chemical dopamine die or are damaged. Dopamine neurons produce a lubricant that helps the brain transmit signals to the body that control muscles and movement. When these cells die or are damaged the result is the shaking and muscle stiffness that are among the common symptoms of the disease.

"We are looking at a way of helping the brain to regenerate the dead or damaged cells that transport dopamine throughout the body," Dr Williams said.

"Peptides help the body heal itself, providing many positive benefits for health, particularly in regenerative medicine; this is why the sports people were using them to recover more quickly in the current doping scandal."

Peptides are both the building blocks and the messengers of the body; the team has used them to mimic the normal brain environment and provide the chemical signals needed to help the brain function.

"Peptides stick together like Lego blocks, so in the first stage of the project we have been able to make a three dimensional material or tissue scaffold that provides the networks cells need to grow; but the peptides also carry instructions in the form of chemical signals which tell the cells to grow into new neurons," Dr Williams explained.

"Importantly, this material has the same consistency as the brain, does not cause chronic inflammation and is non-toxic to the body.

"Our aim is to use this scaffold material to support the patient's own stem cells that could be turned into dopamine neurons and implanted back into the brain. We expect that when implanted the material and stem cells would be accepted by the brain as normal tissue and grow to replace the damaged or dead cells."

While the research is not yet complete, Dr Williams is excited by the possibilities this work offers to the treatment of degenerative conditions.

"It is no secret that we are living longer, and with this we are seeing an increase in many conditions that come about because of ageing such Parkinson's. By developing biomaterials, like the ones we are working on, it could be possible to help the body to regenerate and provide an improved quality of life to the older members of our community," he said.

"This work can also be adapted to other parts of the body which struggle to repair themselves, such as new cartilage for joints, muscle and heart cells, bones and teeth. Ultimately, it will be like taking your car to the garage to have new parts fitted to replace the worn out ones."

The results of the first stage of this Australian Research Council funded project will be published in the international journal Soft Matter.


Treatment - New Drugs May Improve Quality of Life for PD Patients


New Drugs May Improve Quality of Life for Parkinson’s Patients

Copied from The Northwest Parkinson’s Foundation Weekly News Update


Rick Nauert - New research presented at the American Academy of Neurology’s Annual meeting could lead to improved management of Parkinson’s disease.

Experts reported on new medications that mitigate blood pressure problems, address reduced efficacy of the widely used drug levodopa, and provide an option when traditional therapy fails.

“All of these treatments are promising news for people with Parkinson’s disease, which is the second most common neurodegenerative disease after Alzheimer’s disease,” said Robert A. Hauser, M.D., M.B.A., an author of all three studies.

The first study dealt with the rapid drop in blood pressure that people with Parkinson’s can experience when standing up, which can lead to dizziness, fainting and falls.

The problem, which affects about 18 percent of people with the disease, occurs because the autonomic nervous system fails to respond to changes in posture by releasing enough of the chemical norepinephrine.

Researchers randomized 225 people to receive either eight weeks of stable dose treatment with a placebo or the drug droxidopa, which converts to norepinephrine.

After one week of stable treatment, those who received the drug had a clinically meaningful, two-fold decrease in the symptoms of dizziness and lightheadedness, when compared to placebo. They also had fewer falls, or 0.38 falls per patient per week, compared to 1.73 for those receiving a placebo on average over the entire 10-week study duration.

The second study looked at treatment with a new drug for “wearing-off” that occurs with people who have been taking levodopa for several years. As each dose wears off, people experience longer periods of time where the motor symptoms do not respond to levodopa.

In this study, 420 people who were experiencing an average of six hours of “off” time per day received a placebo or one of four dosages of the drug tozadenant in addition to their levodopa for 12 weeks.

People receiving two of the dosages of the drug had slightly more than an hour less off time per day at the end of 12 weeks than they had at the start of the study. They also did not have more troublesome involuntary movements, called dyskinesia, during their “on” time.

The final study involved 321 people with early Parkinson’s disease whose symptoms were not well-controlled by dopamine agonist drugs like levodopa that activate receptors of the neurotransmitter.

For the 18-week study, the participants took either the drug rasagiline or a placebo in addition to their dopamine agonist. Rasagiline also increases levels of dopamine but through a different neural mechanism.

At the end of the study, those taking rasagiline had improved on a Parkinson’s disease rating scale. In addition, rasagiline was well-tolerated with adverse events similar to placebo.

Source: American Academy of Neurology


Treatment - Stem Cell-derived Neurons Renew Cognitive Function: Study #


Parkinson’s: Stem Cell-Derived Neurons Renew Cognitive Function: Study

Copied from The Northwest Parkinson’s Foundation Weekly News Update - Sanford-Burnham researchers convince transplanted stem cell-derived neurons to direct cognitive function—getting us a step closer to using these cells to treat Parkinson’s disease, Alzheimer’s disease and other neurodegenerative conditions.

Researchers and patients look forward to the day when stem cells might be used to replace dying brain cells in Alzheimer’s disease and other neurodegenerative conditions. Scientists are currently able to make neurons and other brain cells from stem cells, but getting these neurons to properly function when transplanted to the host has proven to be more difficult. Now, researchers at Sanford-Burnham Medical Research Institute have found a way to stimulate stem cell-derived neurons to direct cognitive function after transplantation to an existing neural network. The study was published in the Journal of Neuroscience.

“We showed for the first time that embryonic stem cells that we’ve programmed to become neurons can integrate into existing brain circuits and fire patterns of electrical activity that are critical for consciousness and neural network activity,” said Stuart A. Lipton, M.D., Ph.D., senior author of the study. Lipton is director of Sanford-Burnham’s Del E. Webb Neuroscience, Aging, and Stem Cell Research Center and a clinical neurologist.

The trick turned out to be light. Lipton and his team—including Juan Piña-Crespo, Ph.D., D.V.M., Maria Talantova, M.D., Ph.D., and other colleagues at Sanford-Burnham and Stanford University—transplanted human stem cell-derived neurons into a rodent hippocampus, the brain’s information-processing center. Then they specifically activated the transplanted neurons with optogenetic stimulation, a relatively new technique that combines light and genetics to precisely control cellular behavior in living tissues or animals.

To determine if the newly transplanted, light-stimulated human neurons were actually working, Lipton and his team measured high-frequency oscillations in existing neurons at a distance from the transplanted ones. They found that the transplanted neurons triggered the existing neurons to fire high-frequency oscillations. Faster neuronal oscillations are usually better—they’re associated with enhanced performance in sensory-motor and cognitive tasks.

To sum it up, the transplanted human neurons not only conducted electrical impulses, they also roused neighboring neuronal networks into firing—at roughly the same rate they would in a normal, functioning hippocampus.

The therapeutic outlook for this technology looks promising. “Based on these results, we might be able to restore brain activity—and thus restore motor and cognitive function—by transplanting easily manipulated neuronal cells derived from embryonic stem cells,” Lipton said.

The research for this study was funded by the California Institute for Regenerative Medicine (Comprehensive Grant RC1-00125-1) and the U.S. National Institutes of Health (Eunice Kennedy Shriver National Institute of Child Health & Human Development grant P01 HD29587; National Institute of Environmental Health Sciences grant P01 ES016738; National Institute of Neurological Disorders and Stroke grant P30 NS076411; National Eye Institute grants R01 EY05477, and R01 EY09024).

Study Authors are; Piña-Crespo JC, Talantova M, Cho EG, Soussou W, Dolatabadi N, Ryan SD, Ambasudhan R, McKercher S, Deisseroth K, & Lipton SA (2012). High-Frequency Hippocampal Oscillations Activated by Optogenetic Stimulation of Transplanted Human ESC-Derived Neurons. The Journal of Neuroscience, 32 (45), 15837-42 PMID: 23136422

Guest Author Dr. Heather Buschman, Ph.D., is the Scientific Communications Manager at Sanford-Burnham Medical Research Institute in La Jolla, Calif., where she writes about research news in cancer, stem cells, diabetes, obesity and more.

Jim Donahue


Treatment - Northwestern Researchers Develop Milestone Parkinson's Treatment


Northwestern Researchers Develop Milestone Parkinson's Treatment

Copied from The Northwest Parkinson’s Foundation Weekly News Update


Ally Mutnick, Assistant Campus Editor

The Daily Northwestern - Northwestern researchers are continuing tests on their breakthrough development in the fight against Parkinson’s disease, a degenerative disorder that affects movement and coordination.

Toward the end of last year, chemistry Prof. Richard Silverman, and Dalton James Surmeier, chair of physiology at the Feinberg School of Medicine, created with their team a new family of compounds that could slow the progression of the disease.

So far, the compound has only been tested on animals, but experiments have produced successful results. However, researchers are now doing additional animal testing and working on turning the compound into a pill form, according to a Feb. 6 Chicago Tribune article.

The researchers believe their work can slow the disease without any serious side effects. Current treatment for Parkinson’s only targets the symptoms.

The new compound targets a rare faulty membrane protein that allows calcium to flood the dopamine neurons in the brain. These neurons control movement, and calcium interaction from Parkinson’s causes the cells to die, possibly leading to aging and premature death.

The researchers’ compound will selectively target the faulty protein and block calcium entry to stop cells from dying.

Surmeier and Silverman published their findings in the scientific journal Nature Communications on Oct. 23.




Northwestern Researchers Develop Milestone Parkinson's Treatment

Copied from The Northwest Parkinson’s Foundation Weekly News Update


Ally Mutnick, Assistant Campus Editor

The Daily Northwestern - Northwestern researchers are continuing tests on their breakthrough development in the fight against Parkinson’s disease, a degenerative disorder that affects movement and coordination.

Toward the end of last year, chemistry Prof. Richard Silverman, and Dalton James Surmeier, chair of physiology at the Feinberg School of Medicine, created with their team a new family of compounds that could slow the progression of the disease.

So far, the compound has only been tested on animals, but experiments have produced successful results. However, researchers are now doing additional animal testing and working on turning the compound into a pill form, according to a Feb. 6 Chicago Tribune article.

The researchers believe their work can slow the disease without any serious side effects. Current treatment for Parkinson’s only targets the symptoms.

The new compound targets a rare faulty membrane protein that allows calcium to flood the dopamine neurons in the brain. These neurons control movement, and calcium interaction from Parkinson’s causes the cells to die, possibly leading to aging and premature death.

The researchers’ compound will selectively target the faulty protein and block calcium entry to stop cells from dying.

Surmeier and Silverman published their findings in the scientific journal Nature Communications on Oct. 23.




Treatment - Team Support Aids Parkinson's Patients


Team support aids Parkinson’s patients

Copied from The Northwest Parkinson’s Foundation Weekly News Update


Eleanor McDermid - A randomized controlled trial demonstrates improved outcomes if patients with Parkinson's disease (PD) are cared for by a multidisciplinary team.

Researchers compared quality of life and motor functioning in patients cared for by a general neurologist and those cared for by a multidisciplinary team comprising a movement disorders specialist, PD nurses, and a social worker.

"Because the multidisciplinary team included a movement disorders specialist, we cannot be certain whether the group difference in outcome was the result of the 'team' aspect or the 'specialist' aspect of the intervention," say study author Mark Guttman (University of Toronto, Ontario, Canada) and co-workers.

They suggest that the next step should be to compare outcomes for patients treated by a general neurologist with and without a team. "Studying a movement disorders specialist plus a team versus a movement disorders specialist risks the possibility of a ceiling effect," they note, also observing that movement disorder specialists are often in short supply and may be best reserved for the most challenging cases.

During the 8 months of the intervention, quality of life on the Parkinson's Disease Questionnaire (PDQ-39) worsened slightly among the 49 patients receiving usual care from a neurologist, by an average of 1.4 points. By contrast, scores improved by 2.5 points among the 51 patients assigned to multidisciplinary care, creating a significant 3.4-point difference between the groups.

"Such an improvement will be clinically meaningful to patients," the researchers write in Movement Disorders.

The patients were unavoidably aware of their group allocation, but were asked not to reveal it to any clinician, and the researchers who assessed the patients were not aware of which group they were in.

Multidisciplinary care was associated with significant improvements in the PDQ-39 subscales assessing mobility, activities of daily living, and emotional wellbeing, but not in those measuring stigma, social support, cognition, communication, and bodily discomfort.

The secondary outcome of change on the Unified Parkinson's Disease Rating Scale was also significantly influenced by group allocation, with patients in the multidisciplinary care group having a 2.7-point improvement compared with a 1.6-point deterioration in the control group.

"This improvement falls within the range of effect sizes reported in several clinical trials of dopaminergic medication," say Guttman et al. "Although direct comparisons with drug trials are difficult, the observed change in motor functioning appears clinically relevant for patients."

Tertiary outcomes covering depression and psychosocial functioning were also improved in patients assigned to multidisciplinary rather than usual care.

Licensed from medwireNews with permission from Springer Healthcare Ltd. ©Springer Healthcare Ltd. All rights reserved. Neither of these parties endorse or recommend any commercial products, services, or equipment.


Treatmant - Glutathione and Parkinson's


Glutathione and Parkinson's



Glutathione is a molecule and potent antioxidant found in our cells. Glutathione is produced by our bodies and levels decrease with aging, many diseases and Parkinson’s disease. Glutathione is a potent antioxidant in the brain, and the loss of glutathione is one of the earliest reported changes in Parkinson’s disease (PD). In all of us, the brain, like other tissues, is constantly producing free radicals, negative by-products of metabolism that need to be eliminated in order to maintain optimum health. The role of glutathione is to eliminate these free radicals; in essence, putting out a fire. It is unclear whether the low glutathione content in the PD substantia nigra is due to impaired production, or because the burden of free-radicals is excessive. Regardless, clinicians and researchers are asking the question, “Can we treat Parkinson’s disease by replenishing brain glutathione levels?”


The first study was published in 1996 by Italian researchers who administered intravenous (IV) glutathione twice daily to 9 individuals with early, untreated PD. There was a 42% reduction in PD symptoms at the end of the 30-day study, and the therapeutic effect was observed to last for 2-4 months. (Sechi G, et al. 1996) The study has had little impact on PD care because it was small and no placebo was used, but this promising preliminary data has not gone unnoticed.

Since the publication of this study, IV glutathione has gained popularity among complementary and alternative medicine (CAM) providers. Dr. David Perlmutter, a neurologist in Florida and an avid proponent of the therapy, claims that 1400 mg IV glutathione administered 3x/ week is able to reduce PD symptoms. 

In 2009, researchers in Florida conducted a preliminary study to determine whether Dr. Perlmutter’s IV protocol showed benefit compared to placebo. Over the four weeks of the study, individuals receiving IV glutathione had a mild improvement in symptoms, while those receiving the placebo did not. When glutathione was stopped, the individuals receiving glutathione lost the symptomatic improvement, and returned to their baseline level of symptoms. (Hauser RA, et al. 2009) It is important to note that the differences between these two groups were not significant. While the study is small and only provides preliminary data, it is promising non-the-less.

Mechanism of Action

Both of the studies published thus far ask the question, “Does glutathione improve symptoms in PD?” This is a topic of debate in the medical community, because no one has been able to propose a mechanism by which glutathione might offer symptomatic relief.   Continued interest in glutathione  explores this molecules anti-oxidant properties.   The loss of glutathione in the substantia nigra precedes PD symptoms by more than a decade, and occurs prior to the formation of Lewy bodies, considered a PD precursor. Just because low glutathione levels correlate with PD severity, doesn’t mean that the loss of glutathione causes the disease. This is highlighted by the fact that glutathione is decreased in many diseases including cancer, vascular disease and other diseases of aging. We have no idea whether glutathione has the potential to retard disease progression, as the study has not yet been done.

Future Research

More information is needed to determine if glutathione is helpful in Parkinson’s disease. Although studies to date showed no significant difference between placebo treatments in glutathione many questions are still unanswered such as the optimal dose, timing of treatment in relation to disease severity, and duration of treatment. This author has received NIH funding to study glutathione in PD patients, using an intranasal delivery system. Spraying fluid into the nostrils provides a delivery mechanism that is less invasive, less expensive, can be administered at home, with the hopes of more direct access to the brain.   Because of the novelty of the approach, the first step is to ask, “Is intranasal glutathione safe and tolerable in individuals with PD


Oral GSH is available over the counter at most health food stores. However, since glutathione is made up of amino acid precursors (similar to proteins),it is broken down in the gut prior to absorption and therefore little is available for use. It is for this reason that treatments focus on intravenous or IV (administered directly into the bloodstream through the vein

Intravenous glutathione is readily available in most cities, and most providers are using the dosing schedule recommended by Dr. Perlmutter.   IV administration requires frequent trips to your provider’s office and the treatment takes about 20 minutes.  

The therapy is experimental and therefore not covered by most insurance plans.   The estimated cost for IV glutathione therapy runs between $40-$75/ injection, approximately $7,800 per year. The cost for intranasal glutathione is $30-45 per month, approximately $400 per year.   Glutathione is purchased from compounding pharmacies and requires a prescription from a licensed health care provider.


Glutathione is the most abundant antioxidant in the human body, numerous studies have demonstrated its safety when given as a supplement (oral or IV), and the FDA classifies glutathione as “Generally Regarded as Safe.” (GRAS)   Reported side effects are few and far between, and typically have more to do with the administration of glutathione than the medicine itself, i.e. bruising at the IV site or nasal irritation from the spray. Recently, a group of physicians reported a case of severe liver injury in a Japanese man with PD who was receiving 1,200 mg intravenous glutathione daily for 5 months.   The patient discontinued use of IV glutathione, and gradually recovered. (Naito Y, et al. 2010)


Might glutathione be that long-sought ticket to neuroprotection? Will we find a way to measure glutathione levels in the brain a decade before the first signs of disease occur? If so, can we supplement glutathione and stave off the disease? Might we be able to slow or stop disease progression in those already diagnosed with PD? Well controlled clinical research trials are the first step in answering these questions. The next decade holds tremendous promise for this and other therapies targeting protection of neurons. It’s exciting that this small, inexpensive, naturally occurring molecule is paving the way, and that some of this research is happening locally.

Author: By Laurie K Mischley, ND

Comment by Dr. Giroux: Glutathione is a powerful antioxidant that protects our cells from the damaging effects of free radicals or highly reactive oxidative species produced by our cells. There are theoretical reasons to believe that this molecule can protect cells from damage. Research does not yet support the statement that glutathione is neuroprotective in people with Parkinson’s disease. Intravenous glutathione treatments are expensive, often marketed as neuroprotective yet without scientific support. Dr. Mischley and other scientists are researching this molecule and only through their continued diligence will we understand its true effect. Participation in well designed clinical trials is one way to advance our knowledge of this interesting molecule.  


Treatment - Parkinson's Treatment May Boost Creativity #


Parkinson's Treatment may Boost Creativity

Copied from The Northwest Parkinson’s Foundation Weekly News Update


Abigal Klein Leichman - An Israeli neurologist compiled studies on patients who suddenly started drawing, sculpting or writing while on dopamine-stimulating drugs.

Israeli neurologist Dr. Rivka Inzelberg noticed for years that patients taking dopamine-stimulating medication to control symptoms of Parkinson’s disease didn’t bring her the customary box of chocolates at holiday time. Instead they brought drawings, sculptures or poems they’d created despite never having been artistically inclined before.

“I saw it was becoming such a phenomenon, and I looked in the literature to see if anyone ever worked on this,” she tells ISRAEL21c. “I found many articles about patients who have become artists in the context of being Parkinsonian.”

Inzelberg has now written her own article, soon to be published in the journal Behavioral Neuroscience, which reviews and summarizes all the knowledge thus far accumulated about this phenomenon. In the article, she also brings up related questions about the role of dopamine – a brain neurotransmitter that is lacking in people with Parkinson’s – on human creativity.

Inzelberg, who treats patients at the Joseph Sagol Neuroscience Center at Sheba Medical Center and teaches at the medical school of Tel Aviv University, says the connection between dopamine and artistic tendencies has been observed for years.

The artist Vincent Van Gogh suffered from schizophrenia, which is characterized by the overproduction of dopamine. And psycho-stimulants such as cocaine and Ecstasy increase activity of dopamine in the brain.

“People think these drugs help them become more creative, but there is no systematic study that checked this, except anecdotal studies among addicts showing creativity or a high self-measure of talent,” cautions Inzelberg.

Dopamine’s dark side

Too much dopamine may also cause impulsive behaviors, because this brain chemical is responsible for reward-driven behavior and pleasure seeking.

“The feeling of happiness from rewarding activities is transferred by dopamine in the brain,” she explains. “It is possible that in patients with Parkinson’s, when they take these drugs to ease their muscle disability, a side effect can be a need to do things that bring pleasure in a hyper way such as hobbyism or gambling.”

One of the case studies she read involved a medicated Parkinson’s patient who painted compulsively around the clock, but stopped when the dosage was reduced.

Inzelberg stresses that not all Parkinson’s patients on dopamine-stimulating drugs develop creativity or impulsiveness. She and several colleagues are currently building a battery of tests to measure creative skills and impulse control in order to figure out why some patients on dopamine stimulants develop these traits while others do not.

“This is important for a better understanding of the neurological basis of creativity in ‘normal’ humans. Is it possible something else aside from dopamine is influencing this?” asks Inzelberg.

Her main area of interest over the past 25 years of her medical practice has been diseases of the aging brain, including both Parkinson’s and Alzheimer’s. Each of these conditions affects millions of people worldwide.

“I’m interested in the epidemiology of the disease, what changes its onset and course; genetic factors that influence the course of the disease; and also concomitant diseases.”

She explains that people with Parkinson’s disease seem to be protected from all kinds of cancer except for skin cancer; they actually have a higher risk of developing skin cancer. “If we can find why they have such low rates of almost every cancer, this would be significant for saving lives,” Inzelberg says.


Note from John Pepper

As I have only ever taken a Levodopa medication for only a period of three months, and as I have only started painting and writing over the last ten years, I don’t think that, in my case, it was caused by the medication, but has probably got more to do with the Parkinson’s disease itself.



Treatment - No Parkinson's Zone
Treatment - Potential New Class of Drugs Blocks Nerve Cell Death


Potential new class of drugs blocks nerve cell death

Copied from The Northwest Parkinson’s Foundation Weekly News Update


science codex - Diseases that progressively destroy nerve cells in the brain or spinal cord, such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), are devastating conditions with no cures.

Now, a team that includes a University of Iowa researcher has identified a new class of small molecules, called the P7C3 series, which block cell death in animal models of these forms of neurodegenerative disease. The P7C3 series could be a starting point for developing drugs that might help treat patients with these diseases. These findings are reported in two new studies published the week of Oct. 1 in PNAS Early Edition.

"We believe that our strategy for identifying and testing these molecules in animal models of disease gives us a rational way to develop a new class of neuroprotective drugs, for which there is a great, unmet need," says Andrew Pieper, M.D., Ph.D., associate professor of psychiatry at the UI Carver College of Medicine, and senior author of the two studies.

About six years ago, Pieper, then at the University of Texas Southwestern Medical Center, and his colleagues screened thousands of compounds in living mice in search of small, drug-like molecules that could boost production of neurons in a region of the brain called the hippocampus. They found one compound that appeared to be particularly successful and called it P7C3.

"We were interested in the hippocampus because new neurons are born there every day. But, this neurogenesis is dampened by certain diseases and also by normal aging," Pieper explains. "We were looking for small drug-like molecules that might enhance production of new neurons and help maintain proper functioning in the hippocampus."

However, when the researchers looked more closely at P7C3, they found that it worked by protecting the newborn neurons from cell death. That finding prompted them to ask whether P7C3 might also protect existing, mature neurons in other regions of the nervous system from dying as well, as occurs in neurodegenerative disease.

Using mouse and worm models of PD and a mouse model of ALS, the research team has now shown that P7C3 and a related, more active compound, P7C3A20, do in fact potently protect the neurons that normally are destroyed by these diseases. Their studies also showed that protection of the neurons correlates with improvement of some disease symptoms, including maintaining normal movement in PD worms, and coordination and strength in ALS mice.

Of mice and worms

In the ALS mouse model, a highly active variant of the original P7C3 molecule, known as P7C3A20, which the investigators synthesized, largely prevented death of the nerve cells within the spinal cord that are normally destroyed by this disease. The P7C3 molecule also worked, but was not as effective at protecting neurons in this model.

As cell survival increased in the ALS model, coordination and strength of the mice improved as well. Mice that were given P7C3A20 were able to stay on a rotating rod much longer than untreated animals or animals that received the less active compounds. Animals receiving P7C3A20 also performed better in analysis of their walking gait, which typically worsens in these animals as the disease progresses.

In PD, dopamine-producing neurons necessary for normal movement are gradually destroyed. In patients, loss of these brain cells leads to tremors, stiffness, and difficulty walking. The study again showed that P7C3 protects these neurons from cell death and the more active analogue, P7C3A20, provided even greater protection.

The two compounds also potently blocked cell death of dopaminergic neurons in a C. elegans worm model of PD. Moreover, reduced cell death in this model was associated with improved movement in the worms.

Healthy C. elegans worms have a very characteristic swimming motion. This movement is disrupted in the PD worm. Hector De Jesus-Cortes, a graduate student of neuroscience at UT Southwestern Medical Center and lead author of the Parkinson's study, videotaped and analyzed the PD worms' mobility with and without treatment. Normal swimming was almost completely preserved with P7C3A20, and was also fairly well preserved with P7C3.

Tweaking the molecule

The research team compared the activity of several new P7C3-related compounds that they synthesized, in both the hippocampal neurogenesis screen and the mouse model of PD.

"Every variation of our P7C3 molecule that works in the neurogenesis assay also works in the PD model," Pieper says. "As we continue to refine the molecule, our hope is that the results from the neurogenesis assay will accurately predict the neuroprotective potency of the compound, and thus aid in more rapidly optimizing a new neuroprotective agent."

The team plans to continue tweaking the structure of the P7C3 molecule to improve its neuroprotective ability while eliminating potential side effects.

"Our hope is that this work will form the basis for designing a neuroprotective drug that could eventually help patients," Pieper says.

Source: University of Iowa Health Care

The article abstract is here:

The full open-access article is here:


Treatment - Personalized Medicine Closer to Reality


Personalized medicine closer to reality

Copied from The Northwest Parkinson’s Foundation Weekly News Update


Study uses stem cells to study variants of Parkinson’s disease
B.D. Colen

Harvard Gazette - A nationwide consortium of scientists at 20 institutions, led by a principal faculty member at the Harvard Stem Cell Institute (HSCI), has used stem cells to take a major step toward developing personalized medicine to treat Parkinson’s disease.

n part supported by the Harvard Miller Consortium for the Development of Nervous System Therapies, the team of scientists created induced pluripotent stem cells (iPS cells) from the skin cells of patients and at-risk individuals carrying genetic mutations implicated in Parkinson’s disease, and used those cells to derive neural cells, providing a platform for studying the disease in human cells outside of patients.

In a paper published in the journal Science Translational Medicine, the researchers report that although approximately 15 genetic mutations are linked to forms of Parkinson’s, many seem to affect the mitochondria, the cell unit that produces most of its energy.

“This is the first comprehensive study of how human neuronal cells can be models of Parkinson’s, and how it might be treated,” said Ole Isacson, a leader of the study, an HSCI principal faculty member, and a Harvard Medical School professor of neurology, based at McLean Hospital’s Neuroregeneration Laboratory.

The researchers determined that certain compounds or drugs could reverse some signs of disease in the cultured cells with specific genetic mutations, and not in cells with other types of mutations, making real the concept of developing drugs that would be prescribed to patients or individuals at risk for Parkinson’s.

The study was launched with federal stimulus funding provided by the National Institutes of Health (NIH) and was continued with funding from HSCI.

“These findings suggest new opportunities for clinical trials of Parkinson’s disease, wherein cell reprogramming technology could be used to identify the patients most likely to respond to a particular intervention,” said Margaret Sutherland, a program director at NIH’s National Institute of Neurological Disorders and Stroke, in a press release.

The new research indicates that compounds that previously have shown promise in treating Parkinson’s in animal studies, including the antioxidant coenzyme Q10, together with the immunosuppressant rapamycin, have differing levels of effectiveness on various genetic forms of Parkinson’s. Researchers hope that such findings can provide the basis for more specific drugs for individuals with sporadic forms of Parkinson’s.

As Isacson explained in an interview, this study points the way to screening patients with Parkinson’s for their particular variation of the disease, and then treating them with drugs shown effective to work on that variation, rather than trying to treat all patients with the same drugs, as is generally done now.

“We believe that using human stem cells to study the disease is the correct way to go,” Isacson said. “We have the cell type most vulnerable to the disease in a dish. We can study the most vulnerable cells and compare them to the least vulnerable cells. Traditionally, in neurology,” he said, “all patients with the same disease get the same drugs. But they may have the disease for different reasons. This gives us a way to tease out those different reasons, and find different ways to treat them.”

Isacson’s colleagues in the consortium are stem cell scientists Kevin Eggan, Paola Arlotta, and Lee Rubin.