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.


Studies - Eye Damage by Pd


New hope for eyes damaged by Parkinson's disease

Copied from The Northwest Parkinson’s Foundation Weekly News Update

Scientists have discovered a new avenue for the treatment of vision loss, one of the complications of Parkinson's disease.

Medical Press - Gentle, non-invasive treatment with a soft infra-red light can potentially protect and heal the damage that occurs to the human retina in Parkinson's disease, says Professor Jonathan Stone from The Vision Centre and the University of Sydney.

Near infra-red light treatment has long been known to promote the healing of wounds in soft tissues such as skin. Our recent studies are showing that it can also protect the retina of the eye from toxins which attack its nerve cells," Professor Stone said.

"We have been studying a mouse 'model' of Parkinson's disease, in which such a toxin is used to create a Parkinson-like condition. The toxin targets brain cells which use a particular signalling molecule called dopamine, and the infrared light - in the right dose and with the right timing - blocks the toxic effect."

The toxin also kills certain key retinal cells which are important in giving sharpness to the retina's coding of visual images. Infrared light also protects these retinal cells and reduces the damage.

The new results suggest that infra-red radiation will be effective in Parkinson's disease, Professor Stone said. Because the radiation is effective at low intensities, with no known toxicity, there are few barriers if any to trials in humans.

"As shown in these studies on mice, protection or rescue of neurons in the brain - and as we know now, in the retina - is better than the best established treatments for Parkinson's disease," Professor Stone said. "The challenge now is to translate these findings, made in mouse models, to human patients suffering from Parkinson's disease.

"Diseases such as Parkinson's are seriously debilitating; for the individual the need is immediate. There is every reason for clinical trials to be carried out as soon as possible."

As to the potential benefits for Parkinson's patients, he says: "Principally, we anticipate there would be a preservation of acuity, the clarity with which we can see detail and contours in the visual world. The same treatment should be protective for the brain as well, preventing or slowing the otherwise relentless progress of the disease. As always, we will need rigorous trials, to know what can be achieved."

It is no surprise, Professor Stone observed, that the same treatment works for both the brain and the retina. "The retina of the eye is really part of the brain - the only part outside the skull. It has to be outside the skull, so it can function as an eye. In many ways the retina is the most accessible part of the brain, and many discoveries about the brain have begun in the retina.

"Parkinson's is a double-whammy disease," says Professor Stone. "Our dream is turn back both the damage to the brain, and the damage to the retina. Increasingly, this seems possible."

The study 'Survival of Dopaminergic Amacrine Cells after Near-Infrared Light Treatment in MPTP-Treated Mice' by Cassandra Peoples, Victoria E Shaw, Jonathan Stone, Glen Jeffery, Gary E Baker and John Mitrofanis was published in ISRN Neurology in May.

More information: www.ncbi.nlm.nih.g… /PMC3369478/


Studies - Salubrinal


U of M Researchers Study Parkinson's Disease, Treatment

Copied from The Northwest Parkinson’s Foundation Weekly News Update

abc news - University of Minnesota researchers are attempting to slow the onset of Parkinson’s disease and understand more about how it affects people.

The researchers have published two different studies that are aimed at combating Parkinson’s disease and slowing neurodegeneration. They hope to develop a drug that will treat the underlying causes of the disease.

The first study looks at reasons behind the death of neurons in those who have Parkinson’s disease. The researchers believe that a specific protein can build up in the neuron cell that eventually kills it.

The second study looks at the process of how that protein kills the neurons. By targeting this pathway, researchers are learning how to delay the disease onset.

The researchers say that mice treated with Salubrinal had a longer lifespan and a delayed onset of Parkinson’s. Treated animals were also “significantly healthier” and their bodies functioned for longer periods of time.

An outcome of the studies is the conclusion that chronic stress on the endoplasmic reticulum contributes to the onset of Parkinson’s disease and that targeted therapies can help delay its progression.


Studies - Flavonoids


Study Finds Specific Antioxidants May Protect Men Against Parkinson’s Disease

Copied from The Northwest Parkinson’s Foundation Weekly News Update

John Phillip

Live in the - Past research bodies have confirmed the health-protective effect of a natural diet rich in flavonoids to protect against a wide range of diseases including heart disease, hypertension, some cancers and dementia. Researchers from Harvard University and the University of East Anglia have published the result of a study in the journal Neurology that demonstrates how these plant-based phytonutrients can significantly lower the risk of developing Parkinson’s disease, especially in men.

Flavonoids from healthy foods such as berries, tea, apples and red wine cross the delicate blood-brain barrier to protect neurons against neurologic diseases such as Parkinson’s. This large scale study included more than 130,000 men and women participants that were followed for a period of twenty years. During this time, more than 800 individuals developed Parkinson’s disease.

A Diet High in Flavonoids from Berries Lowers Parkinson’s Disease Risk by Forty Percent

After a detailed analysis of their diets and adjusting for age and lifestyle, male participants who ate the most flavonoids were shown to be forty per cent less likely to develop the disease than those who ate the least. No similar link was found for total flavonoid intake in women. Co-lead study author, Dr. Aedin Cassidy noted, “These exciting findings provide further confirmation that regular consumption of flavonoids can have potential health benefits.”

This was the first study to examine the connection between flavonoid consumption and the development of Parkinson’s disease. The findings suggest that a sub-class of flavonoids called anthocyanins may exhibit neuroprotective effects. Participants consuming one or more portions of berry fruits each week were around twenty-five per cent less likely to develop Parkinson’s disease, relative to those who did not eat berry fruits.

Eat 3 to 5 Servings from a Variety of Berries each day to Guard Against Parkinson’s Disease

Flavonoids are the bioactive, naturally occurring chemical compounds found in many plant-based foods and drinks. This study demonstrated the main protective effect was from the consumption of anthocyanins which are present in berries and other fruits and vegetables including aubergines, blackcurrants and blackberries. Strawberries and blueberries are the two most common sources of flavonoids in the US diet, contributing to a twenty-four percent lowered risk in this research.

Parkinson’s disease is among a group of chronic diseases presently affecting one in 500 people, with new cases on the rise. Drug therapies are ineffective and bear significant side effects. The result of this study provides yet another example of the power of a natural diet in the prevention of many debilitating and deadly conditions. Nutrition experts recommend adding a minimum of three to five servings of flavonoids to your diet each week. Include all varieties of berries, apples and green tea to guard against Parkinson’s disease and other neurodegenerative illnesses.

Sources for this article include:

Studies - Latripiridine


Rejected Drug Could Protect Against Parkinson's And Alzheimer's

Copied from The Northwest Parkinson’s Foundation Weekly News Update

Petra Rattue

Medical News Today - The journal Molecular Psychiatry recently featured two studies on latrepiridine, known as Dimebon, which revealed that the second study could be a new potential for the compound to treat Parkinson's, Alzheimer's disease, sleep disorders as well as other neurodegenerative conditions. The international study, which was led by researchers from Mount Sinai School of Medicine, discovered that latrepiridine reduced the level of at least two neurodegeneration-related proteins in mice.

Over 5 million people worldwide suffer from Alzheimer's disease, an incurable, progressive neurodegenerative disease that is the leading cause of dementia in the elderly, whilst around 1 million people in the U.S. suffer from Parkinson's disease, a progressive disorder that leads to muscle stiffness, tremors and slowed movements and gait.

Latrepiridine was approved in Russia in 1983 as an antihistamine. However, in the 90s, researchers discovered that the drug seemed to be effective in the earliest animal models of Alzheimer's disease. A high- profile Phase II clinical trial in Russia demonstrated that latrepiridine showed a considerable and sustained improvement in cognitive behavior in Alzheimer's patients with minimal side effects. A panel of U.S. clinical experts oversaw the trial. The panel included Mary Sano, PhD, Professor of Psychiatry and Director of the Mount Sinai Alzheimer's Disease Research Center. However, later tests of latripirdine in a U.S. Phase III trial failed to show any improvement in those affected by Alzheimer's, which prompted the sponsors to stop further clinical trials of the drug for Alzheimer's disease.

Prior to the failed trials Sam Gandy, MD, PhD, Professor of Neurology, and Psychiatry, and Director of the Mount Sinai Center for Cognitive Health and his team started investigating the way in which latrepirdine functions. Dr. Gandy declares:

"Despite the failure to replicate the positive Russian trial results in U.S. patients, we found unexpected evidence that latrepirdine had potential as a treatment for a number of neurodegenerative disorders. Our study shows that the compound prevents neurodegeneration in multiple ways and should remain a contender for battling these devastating diseases. The anti-amyloid approach - most recently exemplified by reports that a second bapineuzumab trial has failed - might only help patients if begun before the brain pathology begins to build up."

Their new study entailed administering the drug to three different systems, including yeast, mice and mammal cells that all showed a build-up of alpha-synuclein, i.e. a protein that is known to cause neurodegeneration.

They discovered determined that latrepiridine activated autophagy in all three systems, the "self-eating" process of cells that protects the brain from neurodegeneration, which targeted synuclein and protected against its toxicity. They discovered that the drug decreased the amount of synuclein accumulated in the brain of mice through autophagy.

This is the second study published in Molecular Psychiatry by Dr. Gandy's team. Their first study, which appeared in the July 31 issue, revealed that a mice study showed that latrepiridine stopped the toxicity of amyloid-beta protein accumulation by inducing autophagy in animals with Alzheimer's disease. The study entailed randomly administrating latrepirdine or placebo to mice with early stages of Alzheimer's disease, revealed that the drug improved memory through autophagy.

To his surprise, Dr. Petsko, an expert in protein structure, Professor of Neurology and Neuroscience at Weill Cornell Medical College, observed that latrepirdine protects yeast cells from the toxicity of alpha-synuclein and leaves the cells vulnerable so that they can be killed by either the Huntington's disease protein or by either of the two key proteins responsible for ALS-FTD. ALS-FTD is a range of diseases, including Lou Gehrig's disease and frontotemporal dementia.

Petsko stated: "The specificity of latrepirdine protection of yeast cells from alpha-synuclein poisoning was unexpected but highly specific and, we believe, occurs at doses of drug potentially relevant to the clinic."

Dr. Sano of the Mount Sinai Alzheimer's Disease Research Center, continued:

"We believe that the U.S. latrepirdine trial failed because of a lack of understanding of how latrepirdine works. Many of the patients in the Russian trial may have had a subtype of Alzheimer's disease that includes excess buildup of alpha-synuclein, making them more responsive to latrepirdine. We know that this occurs by chance in about one-third of Alzheimer's patients. The data indicating that latrepirdine both stimulates alpha-synuclein breakdown and protects cells from alpha-synuclein poisoning are highly intriguing."

Dr. Gandy and Dr. Yue are currently investigating potential benefits of latrepirdine for treating or preventing disorders linked to high levels of alpha-synuclein like Parkinson's disease, Lewy body dementia, and REM sleep disorder.


Studies - GMI Ganglioside


Promising drug slows down progression of Parkinson`s disease

Copied from The Northwest Parkinson’s Foundation Weekly News Update - Washington: Parkinson’s patients treated with the experimental drug GM1 ganglioside showed improved symptoms during a two and a half-year trial, according to Thomas Jefferson University researchers.

Although the precise mechanisms of action of this drug are still unclear, the drug may protect patients`` dopamine-producing neurons from dying and at least partially restore their function, thereby increasing levels of dopamine, the key neurochemical missing in the brain of Parkinson’s patients.

The research team, led by senior author Jay S. Schneider, Ph.D., Director of the Parkinson’s Disease Research Unit and Professor in the Department of Pathology, Anatomy and Cell Biology and the Department of Neurology at Jefferson, found that administration of GM1 ganglioside, a substance naturally enriched in the brain that may be diminished in Parkinson’s disease brains, acted as a "neuroprotective" and a "neurorestorative" agent to improve symptoms and over an extended period of time slow the progression of symptoms.

What’s more, once the study participants went off the drug, their disease worsened. The study enrolled 77 subjects and followed them over a 120-week period and also followed 17 subjects who received current standard of care treatment for comparison.

"The drugs currently available for Parkinson’s disease are designed to treat symptoms and to improve function, but at this time there is no drug that has been shown unequivocally to slow disease progression," said Dr. Schneider.

"Our data suggest that GM1 ganglioside has the potential to have symptomatic and disease-modifying effects on Parkinson’s disease. If this is substantiated in a larger clinical study, GM1 could provide significant benefit for Parkinson’s disease patients."

GM1 ganglioside is a chemical that is normally found in the brain and part of the outer covering of nerve cells. It plays important roles in neuron development and survival and modulates a wide variety of cell activities. GM1 has been found to rescue damaged neurons and increase dopamine levels in pre-clinical studies, and has been suggested to have beneficial effects in other neurodegenerative conditions.

Because GM1 has effects on many different cellular functions, it seemed a logical approach to try using a drug like GM1 ganglioside to modify the pathological processes occurring in Parkinson’s disease, rather than focusing on a specific potential disease mechanism, said Dr. Schneider.

"Instead of a magic bullet, we think of it like a magic shotgun," he said. "This study was truly a success of translational research."

The study has been published online in the Journal of the Neurological Sciences.


Studies - Focused Ultrasound Waves to Eliminate Tremors


Parkinson's Study Underway at UVA

Copied from The Northwest Parkinson’s Foundation Weekly News Update

Sandy Hausman

WVTF Public Radio - The University of Virginia will soon begin a study that could help people with Parkinson’s Disease. Doctors will use focused sound waves to modify the brain and – they hope – eliminate or reduce tremors.

The University of Virginia is one of many medical centers experimenting with the use of focused ultrasound. Doctors use soundwaves to destroy unwanted tumors and other tissue they can see using magnetic resonance imaging.

So far, they’ve shown that it’s possible to zap pathways in the brain that are causing unwanted movement or tremors. Fifteen patients underwent the bloodless, outpatient procedure and saw improvement in their condition.

Dr. Binit Shah says a second study, involving other medical centers, is planned for people with essential tremor, and another clinical trial – this one involving 30 patients from Virginia – will involve treatment for tremors associated with Parkinson’s Disease.

Already, doctors know that by burning or zapping some sections of the brain, they can reduce unwanted movement, but using focused ultrasound is less invasive.

“So unlike the other types of treatments which all involve making a small hole in the skull and then using a wire to go down into this deeper structure to either leave there and stimulate with electrical signals or to heat up and cause this burn lesion, we can focus these ultrasound beams, to heat up and cause that same lesion," says Dr. Shah.

And it’s possible, he says, that focused ultrasound could treat other problems linked to Parkinson’s.

“We can potentially make lesions in other parts of the brain. They can have different effects – benefits not just with tremor potentially but also some of the other features, like slowness and stiffness.”

Shah says it will take several years to establish the safety and effectiveness of this treatment, and it won’t be widely available until the Food and Drug Administration certifies that focused ultrasound reduces or eliminates tremors and is safe.

Sounds scary to me! John


Studies - Speech


Parkinson's Effect on Speech Fosters Isolation

Copied from The Northwest Parkinson’s Foundation Weekly News Update

Ed Susman

MedPage Today - A new study demonstrated that subtle changes in speech can impact the ability of Parkinson's patients to communicate and may result in further isolation from the community, researchers said here.

Patients participating in the Factors Affecting the Speech of People with Parkinson's Disease Study scored an average 14.8 percentage points lower in their ability to communicate intended emotions compared with controls (P=0.02), Maxwell Barnish, a PhD candidate at University of East Anglia in Norwich, England, and colleagues found.

In his poster presentation at the International Congress on Parkinson's Disease and Movement Disorders, Barnish noted that the communication and emotional conveyance were both predicted by patients' cognitive status as measured by the Montreal Cognitive Assessment.

"Cognitive impairment significantly affects speech and communication in Parkinson's disease," he said. "This leads to reduced communicative participation."

Parkinson's patients were stratified by the median score on the test, and those who scored lower than or equal to 23 also measured 16.7 percentage points lower, on average, in their ability to convey emotion, he told MedPage Today. Cognitive status predicted 19% of the variance in communicative participation, which was statistically significant (P<0.05), he said.

For the study, the researchers recruited 45 people with Parkinson's disease and 29 people who were friends or relatives of the patients. All were from various areas of the U.K. and all were white. The patients were about 70 years of age, and ranged from 48 to 93 years.

The group was not gender-balanced, with a predominance of men in the patients and a predominance of women among the controls. The difference was controlled for in the analysis, Barnish said.

"The majority of Parkinson's patients in this study had mild speech impairments, but this impairment had a substantial impact on everyday communication tasks," Barnish explained. "The qualitative analysis we performed indicated that patients were anxious about their speech and that voices sounded different."

Barnish suggested that their anxiety and perceived voice change might lead to them become less outgoing.

Previous research had not focused on the relationship between cognitive status and everyday communication, hence Barnish attempted to define these relationships.

"Further research is required to determine how these findings can be applied in speech and language therapy for Parkinson's disease," he added.

Alison Yarnall, MD, of the University of Newcastle in England, told MedPage Today, "This is an interesting area of study. Obviously speech and communication are important aspects of daily living that can be interrupted by Parkinson's disease."

"Drugs in Parkinson's disease are well studied with big randomized clinical trials, but things like speech therapy and physical therapy, which can make a massive difference to patients, are often not well studied," she said. Yarnall said she was interested in seeing how further research in the field could impact treatment decisions and resource implementation.

Studies - MSA, Multiple System Atrophy


Kalamazoo frog study yields promise for Atypical Parkinson's disease patients

Copied from The Northwest Parkinson’s Foundation Weekly News Update

Ursula Zerilli - What started as a study observing how contaminants in the Kalamazoo River affect frogs is evolving into Western Michigan University becoming a national leader in finding a cure for a rare human disease.

NFL football players have contributed to the cause and last month, $3,350 raised from an awareness walk attended by 200 people held in Fairborn, Ohio, was given to WMU’s research team because of its growing prominence in finding a cure for multiple system atrophy, a disease unknown to most doctors despite the severity of the symptoms.

The money could have gone anywhere, said donor Frank Cervone, who has accepted the fact that he will eventually die from MSA. But he trusts WMU’s research team will help others live.

Three-in-one killer

MSA is a three-in-one neurological disease, explained WMU biological sciences professor Charles Ide. He said it encompasses Parkinson’s disease, which is life-threatening on its own; cerebellar ataxia, which affects balance and movement abilities, and then autonomic failure sets in, which causes patients to lose control of their automatic body functions, such as breathing or swallowing.

The disease, often known as Atypical Parkinson's disease, affects about 100,000 people, with more than half being middle-aged men. There is no known cause or cure.

“You can’t even swallow your own saliva,” said Ide, who is also director of the Institute and the Great Lakes Environmental and Molecular Sciences Center. “It’s a nasty, terrible disease. Basically, no one knows much about it. Once you actually experience a MSA patient, it breaks your heart. They are paralyzed, can barely move their eyelids and they know exactly what is going on. So, they are totally locked into their bodies.”

“The drug company isn’t working on drugs that don’t have patients and that why it’s called an ‘orphan disease,’ and the government doesn’t fund research for orphan diseases,” he said.

While studying how contaminants in the Kalamazoo River were affecting frogs, Ide and his team found the amphibians developed of a Parkinson’s disease-like syndrome after being injected with PCBs.

The research was performed with new gene-based technology the university acquired, including a DNA microarray system that measures the expression of every coding gene in a genome and a machine that measures the expression of single genes with great accuracy. Ide’s research was highlighted in the Wall Street Journal.

“The idea was contaminants can cause a Parkinson’s like syndrome and they are in the Kalamazoo River, Great Lakes and Lake Michigan. A guy in New York read it and his wife had MSA, he begged me to come to New York and meet her doctor,” Ide said.

Patients step up

The man was Fernando Fajardo and although his wife died from losing her ability to swallow before any research began, he gave $82,500 to begin the MSA project.

While in New York, Ide connected with Dr. Anna Langerveld of Genemakers, LLC, and the Columbia University Medical Center Brain Bank, as well as Vanderbilt University Medical Center. The brain bank agreed to provide MSA and control brain tissue.

The MSA research project uses new genomic and protein-based methods to determine the molecular basis of the disease. Ide, his colleagues and several WMU students use results from testing the brain tissue of deceased MSA patients to identify and learn what gene changes take place in comparison to healthy brain tissue.

“I worked on mice and tissue culture, so we do work on mammals but this is my first human project,” Ide said. “We have two approaches: one is looking at how proteins we know are mis-folded and looking at how those that are mis-folded cause the death of cells. The other is to better understand what these immune cells that shouldn’t be in the brain are doing.”

Ide gives Bob Summers credit for fueling the movement to find a cure for his wife, Sue, who was diagnosed in 2002.

Dr. David Robertson of Vanderbilt University’s Medical School asked Ide to present his 2007 published study on the map of MSA gene expressions versus control brain expressions, an event in which Summers, of Murfreesboro, Tenn., attended.

Raising awareness

“Over the course of the last few years, there have been others who are beginning to step up and put a face on it,” Summers, 65, said. “Sue was in a wheelchair, in hospice and she hadn’t spoken since 2005. I was doing everything for her. She wanted people to see what MSA would do to you. When you experience adversity, you have two choices: to give up or to fight and we chose to fight.”

They decided to organize a Miracles for MSA fundraiser in 2009 and various other fundraisers. Summers is the former high school football coach of retired Pittsburgh Steelers quarterback Fernando Bryant, who also played for the Detroit Lions. Bryant agreed to sponsor their fundraiser and provided signed Steelers Super Bowl Championship footballs to raffle and the event raised $10,000.

“Dr. Ide needed the money. We directed the money that way and we have continued to. He is doing so many good things and when you got a winning horse you stick with it,” Summers said.

Bob’s wife, Sue, survived breast cancer but could not survive MSA, he said. She died on May 4, 2012 at the age of 64. They were married for 47 years. Bob asked that funds be donated in her memory to WMU to support MSA research.

Cervone, who donated the funds from a MSA walk he organized last month, was diagnosed in 2008.

The 50-year-old father of four and former city councilman used to weigh 304 pounds and repossessed semi-tractor trailers for a living, but he says nowadays he is “hugging a lot of carpet.”

“It’s rough. I’m in pain every day. I pass out a lot and am no longer able to drive,” he said. “I’m down to 160 pounds, I had to have a pacemaker implanted to keep my blood pressure up, I have trouble swallowing and my intestinal track became paralyzed.”

Cervone said he’s knows there is not enough awareness about MSA because he has informed doctors who have been practicing medicine for 38 years about his disease and it took two years for him to be diagnosed.

He writes about his experience on an online blog, is working to pass Ohio legislation to make research funds available through the National Institute of Health and he sees a death counselor weekly for a Kettering Medical School Master’s program research project. He hopes to create a MSA organization to provide more consistent funding for research, as well.

“We know it’s too late for us, but we can help them find a cure for newly diagnosed people, so other families don’t go through what we go through,” Cervone said. “I know Dr. Ide will put the time and energy into finding a cure.”

Cure in reach

When Cervone visited campus last month, Ide and his team shared three papers on MSA they will present at the annual meeting of the Society for Neuroscience later this year in New Orleans. Summers said he hopes to visit Kalamazoo to see Ide in the fall.

Ide said over the last decade, about $200,000 has been donated from private and public donors. Because environmental factors are linked to Parkinson’s disease, some of the Environmental Protection Agency’s grants can focus on MSA research, he said.

Donated funds are used to buy supplies instead of paying salaries, he said, and most of the time new money allows his team to purchase a new antibody for research. His team has already used about dozen antibodies for research and expects to look at another nine this summer.

“We buy molecules that help us recognize which proteins are different in MSA brains. Every time you hit on one that shows there’s a function in MSA, you get a better idea of what’s going on in the MSA brain,” he said. “I’m positive a cure is in reach.”

Contact Ursula Zerilli at or 269-254-5295. Follow her on twitter.


Studies - GABA May Explain Pd Puzzle


Harvard Mouse Study May Help Explain Parkinson’s Puzzle

Copied from The Northwest Parkinson’s Foundation Weekly News Update

Rick Nauert PHD - Researchers at Harvard Medical School may have solved the mystery of why the standard treatment for Parkinson’s disease is often effective for only a limited period of time.

Experts say their findings could lead to a better understanding of many brain disorders, from drug addiction to depression.

Investigators used mouse models to study dopamine neurons in the striatum, a region of the brain involved in both movement and learning.

In people, these neurons release dopamine, a neurotransmitter that allows us to perform tasks such as walking, speaking and even typing on a keyboard.

When a person has Parkinson’s the dopamine cells die and the ability to easily initiate movement is lost. Current Parkinson’s drugs are precursors of dopamine that are then converted into dopamine by cells in the brain.

On the other hand, dopamine hyperactivity is associated with drug-seeking behaviours as heroin, cocaine and amphetamines rev up or mimic dopamine neurons, ultimately reinforcing the learned reward of drug-taking. Conditions such as obsessive-compulsive disorder, Tourette syndrome and even schizophrenia may also be related to the misregulation of dopamine.

In a current issue of Nature, Bernardo Sabatini and co-authors Nicolas Tritsch and Jun Ding report that midbrain dopamine neurons release not only dopamine but also another neurotransmitter called GABA, which lowers neuronal activity.

This unsuspected presence of GABA could explain why restoring only dopamine could cause initial improvements in Parkinson’s patients to eventually wane, say the researchers. And if GABA is made by the same cells that produce other neurotransmitters, such as depression-linked serotonin, similar single-focus treatments could be less successful for the same reason.

“If what we found in the mouse applies to the human, then dopamine’s only half the story,” said Sabatini.

The surprising GABA story began in the Sabatini lab with a series of experiments designed to see what happens when cells release dopamine.

The scientists used optogenetics, a powerful technique that relies on genetic manipulation to selectively sensitize cells to light. In laboratory dishes, researchers tested brain tissue from mice engineered to show activity in dopamine neurons.

Typically in such experiments, other neurotransmitters would be blocked in order to highlight dopamine, but Tritsch, a postdoctoral fellow in the Sabatini lab, decided instead to keep the cell in as natural a state as possible.

When Tritsch activated the dopamine neurons and examined their effects on striatal neurons, he naturally expected to observe the effects of dopamine release.

Instead, he saw rapid inhibition of the striatal neurons, making it clear that another neurotransmitter — which turned out to be the quick-acting GABA — was at work.

This was so unusual that the team launched a series of experiments that confirmed GABA was being released directly by these dopamine neurons.

The researchers then tested other transporters, zeroing in on one protein that ferries dopamine and a variety of other neurotransmitters. For reasons they don’t yet understand, this protein — the vesicular monoamine transporter — also shuttles GABA.

“What makes this important now is that every manipulation that has targeted dopamine by targeting the vesicular monoamine transporter has altered GABA as well. And nobody’s paid any attention to it,” said Sabatini.

“Every Parkinsonian model that we have in which we’ve lost dopamine has actually lost GABA, too. So we really have to go back now and think: Which of these effects are due to loss of GABA and which are due to loss of dopamine?”

Anatol Kreitzer, an assistant investigator at the Gladstone Institute of Neurological Disease in San Francisco, who was not involved in the research, called the findings remarkable.

“It was totally unexpected,” said Kreitzer, who is also an assistant professor of physiology and neurology at the University of California, San Francisco.

“At the molecular level, nobody really expected dopamine neurons to be releasing significant amounts of GABA. At the functional level, it’s surprising that this major modulator of plasticity in the brain, which is so critical for Parkinson’s, for learning and rewards, and for other psychiatric illnesses, can also release GABA. That raises a question as to what role GABA has.”

GABA can very quickly change the electrical state of cells, inhibiting their activity by making them less excitable. Sabatini wonders if the loss of GABA in dopamine neurons could explain why hyperactivity is sometimes seen after chronic loss of these neurons.

The next challenge will be to explore whether other neurons that express the vesicular monoamine transporter also release GABA in addition to neurotransmitters such as serotonin and noradrenaline.

Researchers say the finding demonstrates our still infantile knowledge of brain physiology.

“These findings highlight how little we actually know about the most basic features of cell identity in the brain,” said Sabatini.

Tritsch said what started out as a straightforward project to understand dopamine quickly changed direction, with lots of starts and stops on the way to some exciting new findings.

“It can be nice to come up with a hypothesis, test it, verify it, and have everything fall into place,” he said. “But biology rarely works that way.”

Source: Harvard University


Studies - Genes Behid Pd Identified


Genes behind Parkinson’s disease identified

Copied from The Northwest Parkinson’s Foundation Weekly News Update - Washington: Boston University School of Medicine (BUSM) investigators have conducted the first genome-wide evaluation of genetic variants associated with Parkinson’s disease (PD).

The study points to the involvement of specific genes and alterations in their expression as influencing the risk for developing PD.

Jeanne Latourelle, DSc, assistant professor of neurology at BUSM, served as the study’s lead author and Richard H. Myers, PhD, professor of neurology at BUSM, served as the study’s principal investigator and senior author.

A recent paper by the PD Genome Wide Association Study Consortium (PDGC) confirmed that an increased risk for PD was seen in individuals with genetic variants in or near the genes SNCA, MAPT, GAK/DGKQ, HLA and RIT2, but the mechanism behind the increased risk was not determined.

“One possible effect of the variants would be to change the manner in which a gene is expressed in the brains, leading to increased risk of PD,” said Latourelle.

To investigate the theory, the researchers examined the relationship between PD-associated genetic variants and levels of gene expression in brain samples from the frontal cortex of 26 samples with known PD and 24 neurologically healthy control samples.

Gene expression was determined using a microarray that screened effects of genetic variants on the expression of genes located very close to the variant, called cis-effects, and genes that are far from the variant, such as those on a completely different chromosome, called trans-effects.

An analysis of the cis-effects showed that several genetic variants in the MAPT region showed a significant association to the expression of multiple nearby genes, including gene LOC644246, the duplicated genes LRRC37A and LRRC37A2 and the gene DCAKD.

Significant cis-effects were also observed between variants in the HLA region on chromosome 6 and two nearby genes HLA-DQA1 and HLA-DQA1. An examination of trans-effects revealed 23 DNA sequence variations that reached statistical significance involving variants from the SNCA, MAPT and RIT2 genes.

“The identification of the specific altered genes in PD opens opportunities to further study them in model organisms or cell lines with the goal of identifying drugs which may rectify the defects as treatment for PD,” said Myers.


Studies - Triterpenoids Target Nrf2 #


Animal Study Suggests New Class of Antioxidants May Be Beneficial for Parkinson’s

Copied from The Northwest Parkinson’s Foundation Weekly News Update

Rick Nauert

Psych Central - A new powerful class of antioxidants may provide relief from Parkinson’s in the future.

The medication, called synthetic triterpenoids, blocked development of Parkinson’s disease in an animal model.

The trial is discussed in the journal Antioxidants & Redox Signaling , as authored by Dr. Bobby Thomas, a neuroscientist at the Medical College of Georgia.

Thomas and his colleagues were able to block the death of dopamine-producing brain cells that occurs in Parkinson’s by using the drugs to bolster Nrf2, a natural antioxidant and inflammation fighter.

Researchers know that stressors from a variety of sources, be it trauma, insect bites or the simple aging process increases oxidative stress causing the body to respond with inflammation — as a part of the natural healing process.

“This creates an environment in your brain that is not conducive for normal function,” Thomas said.

“You can see the signs of oxidative damage in the brain long before the neurons actually degenerate in Parkinson’s.”

Nrf2, the master regulator of oxidative stress and inflammation, is – inexplicably – significantly decreased early in Parkinson’s. In fact, Nrf2 activity declines normally with age.

“In Parkinson’s patients you can clearly see a significant overload of oxidative stress, which is why we chose this target,” Thomas said. “We used drugs to selectively activate Nrf2.”

Researchers looked at a number of antioxidants already under study for a wide range of diseases from kidney failure to heart disease and diabetes, and found triterpenoids to be the most effective on Nrf2.

Co-author Dr. Michael Sporn, Professor of Pharmacology, Toxicology and Medicine at Dartmouth Medical School, chemically modified the agents so they could permeate the protective blood-brain barrier.

Researchers found that in both human neuroblastoma and mouse brain cells they were able to document an increase in Nrf2 in response to the synthetic triterpenoids.

Their preliminary evidence indicates the synthetic triterpenoids also increase Nrf2 activity in astrocytes, a brain cell type which nourishes neurons and hauls off some of their garbage.

The drugs didn’t protect brain cells in an animal where the Nrf2 gene was deleted, more proof that that Nrf2 is the drugs’ target.

Researchers are now studying the impact of synthetic triterpenoids in an animal model genetically programmed to acquire PD slowly, as humans do.




Studies - Stem Cells #


International Stem Cell Reports Parkinson's Research Advance Stem-Cell Therapy Aimed at Parkinson's Promising

Copied from The Northwest Parkinson’s Foundation weekly News Update

Animal trials by Carlsbad company show progress

Bradely Fikes - Signs of Parkinson’s disease have been relieved in a small animal study conducted by Carlsbad-based International Stem Cell Corp., which is developing its own kind of stem-cell therapy for various diseases.

The study used rats and monkeys to test the therapy’s ability to replace the kind of brain cells destroyed in Parkinson’s and relieve the disease’s movement disorders. The animals were given a neurotoxin to induce Parkinson’s symptoms. Rats showed improved movement, and the monkeys produced higher levels of dopamine, a neurotransmitter essential for movement.

Study results will be presented today at the annual meeting of the American Academy of Neurology at the San Diego Convention Center.

The results indicate the approach is worth pursuing, said study co-author Evan Snyder, who heads the stem-cell and regenerative biology program at Sanford-Burnham Medical Research Institute.

“Being able to show that the cells are there, and that they’re safe, certainly is the first step,” before human testing, Snyder said. “One needs to do monkeys before you can have a treatment.”

Carlsbad-based International Stem Cell is researching therapy with parthenogenetic stem cells, which are made from unfertilized human egg cells. The company says parthenogenetic stem cells present a less questionable approach to stem-cell therapy than using human embryonic stem cells, which are taken from human embryos. The company says parthenogenetic-derived cells are also less likely be rejected by the immune system.

Researchers transplanted the newly produced human brain cells into rats and African green monkeys. Months after treatment, the treated rats moved more normally, and the treated monkeys produced more dopamine. Controls were used in both groups. A total of eight green monkeys were used in the study. Four monkeys were treated, two given a sham treatment and two not given any treatment.

A related study published Friday, in which Snyder was also involved, provided evidence of a more-efficient way of turning human parthenogenetic stem cells into dopamine-producing neurons.

Researchers led by Jeanne Loring at The Scripps Research Institute in La Jolla are pursuing a similar treatment. Loring and colleagues are using induced pluripotent stem cells, artificially produced stem cells that also act like embryonic stem cells. These IPS cells can be produced from skin cells, making it possible to grow the cells directly from patients to be treated. (619) 293-1020 Twitter: sandiegoscience






Studies - Genetic Manipulation of Urate Alters Neurodegeneration


Genetic manipulation of urate alters neurodegeneration in mouse model of Parkinson's disease

Copied from The Northwest Parkinson’s Foundation Weekly News Update

Mike Morrison - A study by Massachusetts General Hospital researchers adds further support to the possibility that increasing levels of the antioxidant urate may protect against Parkinson's disease. In their report published in PNAS Early Edition, the investigators report that mice with a genetic mutation increasing urate levels were protected against the kind of neurodegeneration that underlies Parkinson's disease, while the damage was worse in animals with abnormally low urate.

A study by Massachusetts General Hospital researchers adds further support to the possibility that increasing levels of the antioxidant urate may protect against Parkinson's disease. In their report published in PNAS Early Edition, the investigators report that mice with a genetic mutation increasing urate levels were protected against the kind of neurodegeneration that underlies Parkinson's disease, while the damage was worse in animals with abnormally low urate.

"These results strengthen the rationale for investigating whether elevating urate in people with Parkinson's can slow progression of the disease," says Xiqun Chen, MD, PhD, of the MassGeneral Institute for Neurodegenerative Diseases (MGH-MIND) and lead author of the PNAS report. "Our study is the first demonstration in an animal model that genetic elevation of urate can protect dopamine neurons from degeneration and that lowering urate can conversely exacerbate neurodegeneration."

Characterized by tremors, rigidity, difficulty walking and other symptoms, Parkinson's disease is caused by destruction of brain cells that produce the neurotransmitter dopamine. Healthy people whose urate levels are at the high end of the normal range have been found to be at reduced risk of developing Parkinson's disease. Studies led by Michael Schwarzschild, MD, PhD, director of Molecular Neurobiology Laboratory at MGH-MIND, showed that, among Parkinson's patients, symptoms appear to progress more slowly in those with higher urate levels. These observations led Schwarzschild and his colleagues to develop the SURE-PD (Safety of URate Elevation in Parkinson's Disease) clinical trial, conducted at sites across the country through the support of the Michael J. Fox Foundation. Expected in early 2013, the results of SURE-PD will determine whether a medication that elevates urate levels should be tested further for its ability to slow the progression of disability in Parkinson's disease.

The current study by Schwarzschild's team was designed to improve understanding of how urate protects against neurodegeneration. As in most animals, mice normally have very low levels of the antioxidant because it is broken down by the enzyme urate oxidase or uricase. The higher urate levels seen in humans and great apes were caused by inactivation of the uricase gene during primate evolution. The MGH-MIND team used two strains of genetically altered mice. In one, the gene for uricase is knocked out as it is in humans, increasing urate levels in the blood and brain; in the other strain, the gene is overexpressed, reducing urate levels even lower than usual for mice. Animals from both strains were used in a standard Parkinson's modeling procedure in which a neurotoxin is injected into the dopamine-producing brain cells on one side of the brain.

As expected, the brains of animals with genetically elevated urate levels showed significantly less damage from the neurotoxin injection than did the brains of genetically normal mice. The damage was increased even more in the mice with genetically reduced urate levels, which also exhibited reduced dopamine production and worsened movement abnormalities. The researchers confirmed that genetically altering uricase expression did not affect levels of other molecules in the metabolic pathway that includes urate, supporting attribution of the protective role to urate alone.

"The biology of urate in the brain is largely unexplored," says Schwarzschild, an associate professor of Neurology at Harvard Medical School. "Understanding both urate's mechanisms of protection and the way its levels are regulated in the body will help us determine how to better harness its protective effects, if they are substantiated. We now are searching for the mediators of urate's neuroprotection and beginning to explore how it is generated and transported in different brain cells."

Additional co-authors are Thomas Burdett, Cody Desjardins, Robert Logan, Sara Cipriani, PhD, and Yuehang Xu all of MGH-MIND. The study was supported by grants from the RJG Foundation, the Michael J. Fox Foundation, the American Federation for Aging Research Beeson Collaborative Program, by National Institutes of Health grants R21NS058324 and K24NS060991, and Department of Defense grant W81XWH-11-1-0150.

Studies - Immune Defences Amplify PD Damage

Study finds proof that immune defences amplify Parkinson’s disease damage

Copied from The Northwest Parkinson’s Foundation Weekly News Update

Greg Williams

UAB News - The same mechanism that lets the immune system mount a massive attack against invading bacteria contributes to the destruction of brain cells as part of Parkinson’s disease, according to a study published online today in the Journal of Neuroscience.

Researchers from the University of Alabama at Birmingham (UAB) found that shutting down production of a key group of immune proteins, major histocompatibility complex II (MHCII), completely protected mice that displayed a “human version” of the disease from related nerve cell death.

The MHCII protein complex enables cells that first respond to infections to display pieces of bacteria or viruses on their surfaces for notice by a second part of the immune system. These displayed pieces of invaders trigger a massive, second wave of immune reactions led by T cells and B cells. While vital to body’s ability to combat infectious disease, full-scale immune responses cause disease-related inflammation and cell death when unleashed in the wrong place.

“We were surprised to find that blocking MHCII action rescued nerve cells from Parkinson’s disease mechanisms so quickly and completely,” said Ashley Harms, Ph.D, a postdoctoral scholar in the UAB Department of Neurology within the UAB School of Medicine, and lead author of the study. “The completeness of the rescue argues that this mechanism is at the heart of the immune-mediated aspect of Parkinson’s disease.”

The idea that the immune system plays a major role in Parkinson’s disease has been gaining momentum since September 2010, when a paper published by another group in Nature Genetics found that small changes in the gene for human leukocyte antigen, one piece of the MHCII complex, occurred much more often in patients with Parkinson’s disease.

Parkinson’s disease is the most common neurodegenerative movement disorder, with the steady loss of nerve cells eventually causing patients’ limbs to shake or become rigid. While much about its cause is still unknown, researchers agree than an early step in the disease is the build-up of a protein called alpha-synuclein in nerve cells, which causes them to self-destruct.

Once alpha-synuclein builds up, the question becomes whether immune cells in a given person’s brain will handle the build-up well or ramp up a misplaced, cell-killing immune response. The current study suggests that genes in microglia, the first-responder immune cells of the brain, are triggered to make many more MHCII complexes on their surfaces. This, in turn, enables more T cells to release chemicals called cytokines designed to kill bacteria, but that also destroy nearby human cells.

Conversely, mice genetically engineered to have alpha-synuclein build-up were protected against Parkinsonian nerve cell death when the current study authors shut down their gene coding for the MHCII complex in microglia.

Moving forward Harms and colleagues will seek to learn more about the relationship between MHCII and alpha-synuclein in hopes of informing drug design efforts. The team will, for instance, seek to learn whether it is a piece of alpha-synuclein, or of some related protein, which MHCII displays to trigger a larger immune reaction. They will also shut down the function of each protein in the MHCII complex to see which is most involved in the immune escalation.

“Alpha-synuclein may light the fire, but it appears that inflammation keeps it burning and may be responsible for the progression of Parkinson’s disease from year to year,” said David Standaert, M.D., Ph.D., chair of the UAB Department of Neurology and the study’s corresponding author.

He added that understanding the role of the immune system in Parkinson’s disease is a major research focus with the UAB Department of Neurology. Along with the work on the MHCII complex, another team is looking at whether interfering with an enzyme called leucine-rich repeat kinase 2 or LRRK2 can stop disease progression. LRRK2, like MCHII, is a critical player in the body’s immune response to alpha-synuclein build-up.

Along with Harms and Standaert, Shuwen Cao, Aaron Thome and Xinru Li in the UAB Center for Neurodegeneration and Experimental Therapeutics, Amber Rowse in the UAB Department of Microbiology, Leandra Mangieri and John Shacka in the UAB Department of Pathology, Chander Raman in the UAB Department of Medicine, and Randy Cron in the Division of Rheumatology, part of the Department of Pediatrics at Children’s Hospital of Alabama, made important contributions to the study. The work was supported by the RJG Foundation and the National Institutes of Health.


Studies - 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.

In 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.


Studies - Glutathione

Parkinson Disease: Avoiding glutathione


On April 11, 2012, in Living with Parkinson's, Medicine, NCF in the News, Parkinson People, Uncategorized, by Dr._Sutherland

Like any serious disease, a diagnosis of Parkinson Disease often makes people desperate for anything that will halt the progress or even reverse it.  Extensive scientific studies over many years have shown that several medications and treatments help to relieve the symptoms of PD.  None of these treatments have been shown to effectively slow it down, though several very good, well-designed placebo-controlled studies have been conducted at great expense of time and money.  Some of these studies have been driven by the pharmaceutical industry, some by university research centers, and some by private physician clinics.  The unifying feature of the treatments currently offered by Parkinson’s Disease Clinics and specialists is that they are based on scientific evidence.

Several unapproved, unproven, and potentially harmful treatments have been offered over the years; unfortunately they continue to be offered.  Glutathione is a small molecule, made up of three peptides, that has anti-oxidant properties in the test-tube.

Theoretically, it could reduce oxidation in brain cells, which might help preserve the power-producing organelles called mitochondria.  If one could reduce oxidative damage to mitochondria, brain cells could potentially live longer and be healthier.  If one follows this line of reasoning, neurodegenerative diseases could be slowed down.  An effect such as this would take many years to investigate and hundreds or even thousands of human subjects.  It certainly would not cause an immediate improvement or reversal of symptoms.  To date, there is no good evidence whatsoever that glutathione either treats or slows the progression of PD.  In fact, there is good evidence that GLUTATHIONE DOES NOT WORK.  See the following review

Dramatic videos of immediate improvement in PD signs and symptoms within 20 minutes of infusion demonstrate a placebo effect that is well-known in PD studies.  Just reviewing the proposed mechanism for treatment (anti-oxidation), one can see that dramatic improvement makes no sense; the best one could hope for would be slowed progression.  As they are currently marketed and provided, treatments with IV glutathione should be avoided.

All patients should be very cautious about starting any treatments that have not been studied scientifically, unless they are part of a bonafide scientific trial.  There is an excellent way to get involved in PD studies by going the Michael J. Fox Foundation website and entering information into the Trial Finder portal at




2 Responses to “Parkinson Disease: Avoiding glutathione”

Passia says:

April 12, 2012 at 10:33 am


Your article makes the statement that glutathione doesn’t help Parkinson’s patients. One thing that is not made clear is that you are discussing IV glutathione treatments.

Glutathione that is given intravenously is not able to be transported inside the cell where it is primarily needed by the body. Therefore, the problem lies with the delivery system of the glutathione, and not necessarily with the glutathione itself. There are new products that offer delivery systems for glutathione that support the body to make glutathione inside the cell.

Before making conclusions about glutathione and Parkinson’s, please review the studies that focus on intra-cellular glutathione. It would be a shame to make a conclusion on incomplete information.




2.    Sally says:

October 19, 2012 at 10:46 am


I agree with the previous post by Passia. But, I have a few things I would like to add.

We all can watch the YouTube videos of Parkinson’s patients before and after IV Glutathione. I do not believe this is a placebo effect…or a terrible hoax on the Parkinson’s community.


*Oral Glutathione is a protein and will be broken down in the GI tract.

*The IV Glutathione molecule is too large to penetrate the cell wall.

*If the body is given the correct components to make Glutathione, the body will.

How do we increase Glutathione:

*We can use Whey protein and increase our Glutathione about 35%.

*Cold showers daily will raise Glutathione about 20-25%.

*Lipoic acid increases Glutathione about 30-50%.

*Milk Thistle will raise Glutathione about 35%.

*N-Acetyl Cysteine will raise Glutathione about 85%, but requires 8,000 milligrams a day.

*We can educate ourselves on the research on supplements that is being done to enable our bodies to make more Glutathione…up to 300% more.

Don’t take my word for it… Go to and search Parkinsons (or any other disease) and Glutathione. You will find over 103,000 studies have been done on the benifits of increasing Glutathione in our bodies.

Educate yourself and make your own best decision.





Studies - Melatonin

Melatonin: May Help More Than Just Your Sleep

Copied from The Northwest Parkinson’s Foundation Weekly News Update

Julie Chen M.D. - Most of you have heard of melatonin before, but it's likely that you usually only hear about it in regards to insomnia or sleep issues. What you may not know is that it seems to play a role in other health concerns we frequently hear about, including cancers, hypertension, Alzheimer's disease, and Parkinson's disease, just to name a few.

Melatonin is a compound in our body that helps to regulate sleep as well as other physiological rhythms in our body. It is secreted by the pineal gland and is a hormone that is affected by light. Light suppresses levels of melatonin, while darkness helps to trigger our body to secrete more of this compound. What's interesting about melatonin is that its levels start to wane as we age and certain medications seem to alter its levels in our body as well.

While the long-term side effects of frequently altering our natural melatonin secretion is not completely well understood, there is some concern that long-term alterations to normal secretion patterns can have other negative health effects. That is why sometimes you may hear from the medical community about concerns for night workers and their overall health.

Because melatonin has antioxidant effects in our body, there is growing interest in its benefits for patients with neurodegenerative diseases such as Parkinson's disease or Alzheimer's disease.[1-3] There is even growing interest in using melatonin for stroke patients and those with high blood pressure.[1-4]

Early studies suggest that there may be some benefit from melatonin use in patients with cancer. Some of these studies suggest that patients on melatonin had better response to chemotherapy in breast cancer patients, and some of the side effects and anxiety associated with therapy were somewhat mitigated -- more so in the melatonin users compared to those not on melatonin.[7-12]

There was a meta-analysis of randomized, controlled trials using melatonin as adjuvant therapy or alone for cancer patients, and researchers found that there was a 34 percent relative risk reduction in death in the melatonin user group.[11]

Another study looked at patients who had advanced cancer in the breast, lung, gastrointestinal tract, head or neck. When given chemotherapy either alone or with 20 mg/day of melatonin, there was a reduction in side effects of low platelet count, fatigue, mouth sores, heart complications, and neurotoxicity in the melatonin group, and higher rate of survival.[7-9],[12]

There is even some indication that melatonin may be helpful with migraines. There was a study that looked at migraine sufferers who were given 3mg of melatonin about 30 minutes before bedtime every night for three months. Of the patients who finished the study, two-thirds of the patients seemed to have a 50 percent reduction, and the severity and duration of migraines were less severe.[13]

While these early studies suggest some exciting benefits from regular melatonin therapy, I want to caution you from going out and buying large quantities or dosages of melatonin without first running the idea by your physician. The fact is that these are early studies and that further studies are warranted to help us really get a better understanding of melatonin's comprehensive role in our health. For now, if you are interested in trying out melatonin, make sure to ask your physician about it and whether it is right or safe for you.

Once you have the go-ahead from your doctor, the general rule on dosing is that for those of you looking for help with sleep, a dosage of about 0.5-3mg at bedtime is what you would need for insomnia or sleep issues. You may consider 5-6mg for time zone changes or jetlag but for daily usage, the lower dosages are ideal at about 0.5-3mg at bedtime.

For those looking for help in more complicated health issues such as migraines or cancers, make sure you get clearance from your treating physician first and make sure to take it separately from your prescription medications once you have the clearance to take it. The dosages for these therapeutic goals are usually higher at around 5-20mg. If you would like to utilize higher dosages, my recommendation is to first consult your physician but also seek the guidance of an integrative physician or naturopathic doctor.

While these early studies are truly exciting and indicate a potential wide array of health benefits, I am just as excited as you are to see further studies that will help to clarify more of the intricacies of therapeutic indications as well as safety and side effect profiles above and beyond what we currently already know.


1. Suzen S. Recent developments of melatonin related antioxidant compounds. Comb Chem High Throughput Screen. 2006 Jul;9(6):409-19.

2. Cardinali DP, Furio AM, Reyes MP. Clinical perspectives for the use of melatonin as a chronobiotic and cytoprotective agent. Ann NY Acad Sci. 2005 Dec;1057:327-36.

3. Srinivasan V, Pandi-Perumal S, Cardinali D, Poeggeler B, Hardeland R. Melatonin in Alzheimer's disease and other neurodegenerative disorders. Behav Brain Funct. 2006;2(1):15.

4. Reiter RJ, Tan DX, Leon J, Kilic U, Kilic E. When melatonin gets on your nerves: its beneficial actions in experimental models of stroke. Exp Biol Med (Maywood.). 2005 Feb;230(2):104-17.

5. Scheer FA, Van Montfrans GA, van Someren EJ, Mairuhu G, Buijs RM. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension. 2004 Feb;43(2):192-7.

6. Cagnacci A, Cannoletta M, Renzi A, et al. Prolonged melatonin administration decreases nocturnal blood pressure in women. Am J Hypertens. 2005 Dec;18(12 Pt 1):1614-8.

7. Lissoni P, Barni S, Meregalli S, et al. Modulation of cancer endocrine therapy by melatonin: a phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progressing under tamoxifen alone. Br J Cancer.1995 Apr;71(4):854-6.

8. Cos S, Gonzalez A, Martinez-Campa C, et al. Estrogen-signaling pathway: a link between breast cancer and melatonin oncostatic actions. Cancer Detect Prev. 2006;30(2):118-28.

9. Sanchez-Barcelo EJ, Cos S, Mediavilla D, et al. Melatonin-estrogen interactions in breast cancer. J Pineal Res. 2005 May;38(4):217-22.

10. Sainz RM, Mayo JC, Tan DX, Leon J, Manchester L, Reiter RJ. Melatonin reduces prostate cancer cell growth leading to neuroendocrine differentiation via a receptor and PKA independent mechanism. Prostate. 2005 Apr 1;63(1):29-43.

11. Mills E, Wu P, Seely D, Guyatt G. Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis. J Pineal Res. 2005 Nov;39(4):360-6.

12. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer. 1999 Nov;35(12):1688-92.

13. Peres MF, Zukerman E, da Cunha TF, Moreira FR, Cipolla-Neto J. Melatonin, 3 mg, is effective for migraine prevention. Neurology. 2004 Aug 24;63(4):757.

14. Drake MJ, Mills IW, Noble JG. Melatonin pharmacotherapy for nocturia in men with benign prostatic enlargement. J Urol. 2004 Mar;171(3):1199-202.

15. Brzezinski A, Vangel MG, Wurtman RJ, et al. Effects of exogenous melatonin on sleep: a meta-analysis. Sleep Med Rev. 2005 Feb;9(1):41-50.


Studies - LCIG (Levodopa-carbidopa Intestinal Gel)

Five abstracts evaluating Abbott's LCIG presented at Parkinson's disease congress

Copied from The Northwest Parkinson’s Foundation Weekly Newsletter

News Medical - Today Abbott (NYSE: ABT) announced results from five abstracts evaluating levodopa-carbidopa intestinal gel (LCIG), its investigational compound for advanced Parkinson's disease. The abstracts include the results from the second interim analysis of a long-term safety and tolerability trial, as well as secondary endpoint analyses from the Phase 3 pivotal trial. All of the abstracts were presented at The 16th International Congress of Parkinson's Disease and Movement Disorders, June 17-21 in Dublin, Ireland.

LCIG is currently approved in 40 countries. In the U.S., LCIG is an investigational therapy that is currently being evaluated in patients with advanced Parkinson's disease in additional Phase 3 clinical trials. In these trials, levodopa-carbidopa is administered in gel form, directly into the small intestine via a procedurally-implanted tube connected to a portable pump that delivers continuous supply of LCIG during awake hours.

Long-Term Safety and Tolerability
In a 54 week open-label safety and tolerability study of 354 patients with advanced Parkinson's disease, the primary endpoint of safety showed adverse events (AEs) were mostly mild to moderate, were generally associated with the Percutaneous Endoscopic Gastrostomy (PEG) tube placement procedure and its complications, were transient, and resolved over time.

In the secondary endpoint analysis from the open-label study, patients experienced an average daily "off" time of 6.7 hours, and 7.7 hours of "on" time without troublesome dyskinesia at baseline. "Off" time refers to periods of poor mobility, slowness and stiffness experienced by patients with Parkinson's disease, while "on" time refers to periods of good motor symptom control. At week 54, mean daily "off" time had decreased an average of 4.5 hours, and "on" time without troublesome dyskinesia had increased by 5.1 hours. "On" time with troublesome dyskinesia decreased an average of 0.6 hours.

"Despite the many advances that have been made over the years in treating patients with Parkinson's disease, managing motor complications such as wearing off in the advanced stages of the condition continues to be challenging for physicians, patients and their caregivers," said Dr. C.W. Olanow, M.D., Professor of Neurology and Neuroscience at the Mount Sinai School of Medicine in New York City. "Data from the various clinical trials evaluating LCIG suggest that patients with advanced Parkinson's disease may benefit from continuous intestinal infusion of levodopa and carbidopa."

The most common treatment emergent AEs were complication of device insertion (33.1 percent), abdominal pain (30.0 percent), procedural pain (21.7 percent) and nausea (16.1 percent). The most common serious treatment emergent AEs were complication of device insertion (6.5 percent), abdominal pain (3.1 percent) peritonitis (2.8 percent) and polyneuropathy (2.8 percent). Twenty-six patients (7.3 percent) withdrew due to at least one AE; 17 of these patients withdrew due to at least one serious AE. Gastrointestinal- and PEG-related issues were the most common cause of withdrawal from the study.

Phase 3 Efficacy
Functional and quality of life secondary endpoint analyses from a twelve-week double-blind, double-dummy pivotal trial of 71 patients comparing LCIG to standard levodopa-carbidopa immediate release (LC-IR) tablets were also presented. The primary endpoint of this study showed a reduction in mean daily "off" time of 4.0 hours, a statistically significant difference of 1.91 fewer hours spent in "off" time with LCIG compared to LC-IR tablets. These data were previously presented at the American Academy of Neurology Annual Meeting (April 21-28, 2012, New Orleans, Louisiana). The most common adverse events were complication of device insertion (51 percent), abdominal pain (42 percent), procedural pain (32 percent), nausea (25 percent), constipation (21 percent), orthostatic hypotension (18 percent), post-operative wound infection (17 percent), and incision site erythema (16 percent).

"We are pleased to showcase the clinical trial results being presented for LCIG in patients with advanced Parkinson's disease," said Robert Lenz, M.D., divisional vice president, Global Pharmaceutical Research and Development, Abbott. "Obtaining pivotal and supportive clinical data is a critical stage in the overall development process of LCIG and further supports our efforts to develop LCIG for advanced PD patients in the U.S. who are in need of alternative therapies."

It is estimated that at least three million people worldwide have been diagnosed with Parkinson's disease. As the disease progresses, the effect of oral medications may not last as long and can cause increasing side effects. Patients with advanced Parkinson's disease may experience fluctuations between bradykinetic (slowness of movement) and hyperdyskinetic (involuntary movement) states.

Other abstracts presented were:

Abstract 385: "Randomized, Double-blind, Double-dummy Study of Continuous Infusion of Levodopa-carbidopa Intestinal Gel in Patients with Advanced Parkinson's Disease: Functional and Quality-of-Life Outcomes."

Kiebertz K, et al.; Monday, June 18, 12:45 - 14:15 CET / 6:45 - 8:15 a.m. CDT.
Abstract 436: "Levodopa-carbidopa Intestinal Gel in Parkinson's Disease Patients with Severe Motor Fluctuations: Interim Quality-of-Life Endpoints in an Ongoing, Open-label Study."

Standaert DG, et al.; Monday, June 18, 12:45 - 14:15 CET / 6:45 - 8:15 a.m. CDT.
Abstract 410: "Stable Levodopa Plasma Levels with Jejunal Infusion of Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson's Disease Patients."

Nyholm D, et al.; Monday, June 18, 12:45 - 14:15 CET / 6:45 - 8:15 a.m. CDT.


Studies - Football, Brain Damage

And what of football, the game we love?

Copied from The Northwest Parkinson’s Foundation Weekly News Update

It won't be changed easily, not with its public and personal histories.
Paul Zerby

Star Tribune - Is pro football about to go the way of the gladiators and the lions?

A new study of more than 3,400 National Football League players who played at least five seasons between 1959 and 1988 published in the journal "Neurology" reports a combined death rate from Alzheimer's, Parkinson's and Lou Gehrig's diseases in that cohort of about three times the rate for the general population of American men.

The study didn't deal with a disease known as CTE (for chronic traumatic encephalopathy), and of the 334 of the group who had died by the end of 2007, it is thought some may have died from CTE.

Now the NFL has pledged a $30 million grant to the National Institutes of Health to study the brain, specifically CTE, concussion management and treatment, and the relationship between traumatic brain injury and late-life neurodegenerative disorders, especially Alzheimer's.

The league's commissioner, Roger Goodell, has been quoted as saying, "We hope this grant will help accelerate the medical community's pursuit of pioneering research to enhance the health of athletes past, present and future," and observing that the NIH study is designed to help not only athletes but the general population, especially the military.

The Vikings' former great All-Pro defensive end, Carl Eller -- one of the anchors, along with Jim Marshall, of the Purple People Eaters, and now the board chair for the NFL Retired Players Association -- argues that the money will benefit current and future players and should be more focused on retired players.

One hopes that no generation of players will end up being compared to the tragic Tuskegee experiment. George Will, with whom I seldom agree, recently wrote: "Football is entertainment in which the audience is expected to delight in gladiatorial action that a growing portion of the audience knows may cause the players degenerative brain disease. Not even football fans, a tribe not known for savouring nuance, can forever block that fact from their excited brains."

All my life I've been a football guy, playing on grassy yards from Fargo to Duluth to St. Paul to Minneapolis and the suburbs, with no equipment at all other than a neighbourhood football. In late grade school, I weighed more than 100 pounds, but not more than 112, and played fullback for the Randolph-Snelling Midgets.

We wore shiny red-and-white jerseys furnished by a kindly drug store owner and won many of our games. We were scared to death of the Hallie Q. Brown team, reputed to be the super athletes that all black kids were, but managed to stumble to a tie with them. I even got my name in the paper for plunging for the extra point.

By the time I played offensive and defensive guard for the Cretin B-squad football team, I was up to around 125 pounds and stood over 5-foot-9. My B-squad football letter turned out to be the apex of my athletic career. Still, when years later my wife, unbeknownst to me, gave away my letter sweater, it was the nearly the end of a beautiful marriage.

I have also been an ardent fan since I can remember. I am often not so gently ridiculed at family gatherings when I share my memories of, as a small child held in my father's arms, watching the college all-stars play the Chicago Bears. I came close to death by appendicitis while listening to the Army-Notre Dame game when Army had Mr. Inside, Doc Blanchard, and Mr. Outside, Glen Davis, and clobbered my beloved Irish.

As a Boy Scout, I was privileged to usher for Gopher games at the old Memorial Stadium. (It was a lot like the TCF Bank Stadium, but with the seats farther from the field.) I got to watch Bud Grant, Leo Nomellini, Clayton Tonnemaker, Billy Bye and others who have faded into the obscurity of my failing memory.

Later, as a student at the U, I traveled down to Iowa City to watch some guy named Paul Giel, who eventually was instrumental in getting Memorial Stadium torn down in favor of the Metrodome, an awful baseball venue where I saw a couple of World Series, but a perfectly fine stadium for football.

A lot more comfortable than the old Met Stadium, where I purchased season tickets for the Vikings in 1962 that are still in my name, and where we bundled up in sleeping bags to watch Eller and Marshall and the Vikes play the game outdoors, where God intended.

Mr. Will doesn't seem to understand that watching football is an addiction; I will most likely continue to see some games as long as I can turn on the television and now and then get to a stadium. This week the competition wasn't only between the Cowboys and the Giants, but between the game and Bill Clinton at the Democratic National Convention. But I'm afraid Will is right about the heart of the matter.

Oh, well -- there's always politics, for those of us who love contact sports. html