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Wednesday, June 8, 2016

Augusta University research seeks better drug for Parkinson's

Researchers aim for reduced side effects


Dr. Bobby Thomas, a neuroscientist at AU, said the treatment being researched appears to be "much safer" than a multiple sclerosis drug.

June 7, 2016

As a longtime member of South Ca­ro­lina’s boxing commission and a friend to many great athletes and boxers, Paul Kennemore can tell a lot of stories, such as what Joe Frazier told him about Muhammad Ali and their historic battles.

“Joe said, ‘He never shut up, all three fights,’” Kennemore said, cracking up his neurologist John Mor­gan and the staff in a room at the Move­ment Disorders Clinic at AU Medi­cal Center. Like Ali, Kennemore has Parkinson’s disease, but he is doing pretty well. 
“The biggest thing is getting around now when the medicine wears off and you get tied up,” said Ken­nemore, 68, of Waterloo, S.C. “Overall I’ve been doing good, just blessed.”
Despite “millions” in research over the years, doctors still rely on medications to essentially try and replace the dopamine that dying nerves are no longer producing and have yet to find anything that slows the progression of the disease, Morgan said.
But in a study published today in the Journal of Neuroscience, Morgan and fellow Augusta University researchers are looking at a metabolite similar to established drugs that might have the protective effects on nerve cells without the significant side effects of the established drugs.
The researchers are looking at a metabolite called monomethylfumarate, which is very similar but slightly different than what is in Tecfidera, a drug used in patients with multiple sclerosis. Both drugs appear to stimulate a key protein that can trigger genes involved in antioxidant, anti-inflammatory and cell protective pathways, but the experimental metabolite appears to do it without having some of the significant side effects of the MS drug, which can cause constipation and flushing. Con­sti­pation is already a problem in Parkinson’s disease.
“You don’t want to intervene with a drug that would have these complications,” said Dr. Bobby Thomas, a neuroscientist at AU. “That’s why our study is a little bit more important because we find that the (new) metabolite appears to be much safer.”
Morgan said he was “very excited because NIH and other funders are always looking for new possibilities to treat Parkinson’s, Alzhei­mer’s, other neurodegenerative diseases where we don’t have any kind of treatment that modifies the disease.”
The metabolite is also part of a drug that has already been approved by the Food and Drug Administra­tion to treat psoriasis and is similar to the MS drug, so that might help if it is to be developed as a new drug, Morgan said.
“Repurposing of drugs is a classic mechanism because often if the patient population is the same, in the same age range, you have a lot of data there,” he said.
Antioxidants such as vitamin E have been tried in Par­kin­son’s disease clinical trials and failed, but targeting a mechanism in that same gene pathway might be a way to get a better response, Tho­mas said.
“We believe that this may be a better approach,” he said.
The next step might be to pursue clinical trials, but the Augusta researchers said there is more basic science to be done on other metabolites that act in the same pathways but might work a little better. Morgan cautions that the work was done in mice and that many drugs that appear promising in animals fail to produce in human clinical trials.
“Translation into humans is a whole, bigger ball of wax,” he said.
But Morgan told Kenne­more he hoped their work might be helpful down the road and, in the meantime, Ken­nemore is doing “really, really good.”
A boxer himself at one time, Kennemore said he has seen the toll the boxing greats like Frazier and Ali paid for their historic bouts.
“You can go through a lot of battles,” he said, “but you can’t go through a lot of wars.”
http://health.einnews.com/article/329900452/a8fg83uxr8W2FrdX

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