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Research casts doubt on Parkinson's disease treatment
Wednesday September 04, 2013
Recent study finds that increase in a brain protein can worsen symptoms, opposite what doctors have long believed
Chicago Tribune - A recent study questions long-held assumptions about the way a brain protein affects the progression of Parkinson's disease.
Researchers in 1997 linked Parkinson's with the protein alpha-synuclein. They began looking for ways to block it to slow the progression of the disease, which is characterized by such symptoms as tremors, rigidity, trouble walking and slowness of movement and affects more than a million Americans.
Demetrius Maraganore, a neurologist at NorthShore University HealthSystem in Evanston, has been working with Mayo Clinic researchers to study that brain protein, focusing on its relationship to two key effects of Parkinson's disease: motor and cognitive impairment and dementia.
Maraganore said the recently released study of 1,098 Mayo patients over 15 years suggests that lowering alpha-synuclein may have the opposite effect of what doctors have long thought. Rather than help, that treatment may increase the risk of Parkinson's patients becoming physically incapacitated and demented, he said.
The study found that patients with a lower amount of alpha-synuclein had a 23 percent greater risk of becoming wheelchair dependent or developing dementia, Maraganore said. The finding runs counter to a clinical trial underway in Vienna that's designed to reduce alpha synuclein in Parkinson's patients.
Maraganore said it appears that alpha-synuclein has a dual and opposite effect. His study suggests that before a person develops Parkinson's, less alpha-synuclein is good and reduces the risk for developing the disease. But it seems that once the disease is contracted, less of the protein is bad, posing a greater risk for motor impairment or dementia, he said.
Katerina Markopoulou, a neurologist at NorthShore and an author of the study, said this is the first time they observed that more alpha-synuclein increased the risk for developing Parkinson's disease and less alpha-synuclein resulted in worse motor and cognitive skills.
"This raises concerns about the efficacy and safety of therapies designed to reduce alpha-synuclein expression in Parkinson's disease," Markopoulou said.
Todd Sherer, a doctor and CEO of The Michael J. Fox Foundation for Parkinson's research, said that although this study may be an important contribution in the field, it does not change his view of the importance of the Vienna clinical trial.
The Vienna study "hasn't changed our view of the importance of targeting alpha-synuclein as a therapeutic strategy," Sherer said. "There are studies that show the opposite of what Dr. Maraganore is showing. The jury is out. This is a scientific process playing out, and we are really excited by this area of research around alpha-synuclein for developing treatment. We hope to learn a lot from it and move forward with alpha-synuclein as a strategy."
Parkinson's is a degenerative disease of the nervous system. Approximately 20 percent of people who have it will develop Parkinson's disease dementia. There are an estimated 7 million to 10 million people with the disease worldwide, and about 60,000 are diagnosed each year. There is no cure, although medications can treat symptoms.
Maraganore has discussed the new study with colleagues, learning that they have anecdotal evidence from their patients that support his findings.
"This is the first large genetic association study of alpha-synuclein and longitudinal outcomes in Parkinson's disease," said Eric Ahlskog, a Mayo author on the study. "If replicated, this research may change the treatment paradigm focused on alpha-synuclein reduction for Parkinson's disease."
Maraganore thinks more trials and observational studies are needed, as they can provide information for much longer periods of follow up than clinical trials, at a fraction of the cost.
Paul Ruby, of Geneva, was diagnosed with early-onset Parkinson's disease in 2006 and is the founder of the Paul Ruby Foundation for Parkinson's Research. Since its inception, the foundation has raised more than $500,000.
Ruby remains optimistic about finding a cure, saying that even small grants for research make a difference. His foundation funded a project at Northwestern University's Parkinson's Disease and Movement Disorders Center having to do with sleep and Parkinson's disease.
But Ruby cautions about where to direct research funding in light of what this new study found.
"It's critical they don't spend time, money or energy on therapies that may not be working," Ruby said. "Especially if there is more anecdotal evidence; it's counterproductive."-
Anne Cohn Donnelly, 68, of Winnetka, was diagnosed with Parkinson's disease more than two years ago. Donnelly, a doctor of public health, said her handwriting became tiny, her voice got quiet and her toes curled. A visit to her regular doctor suggested she have further tests.
Donnelly is frustrated that there is no proven way of slowing or preventing the disease.
"There is a lot of money put into finding what is wrong, but there are still no definitive answers," she said.
Funding agencies have invested hundreds of millions of dollars on research studies of alpha-synuclein, Maraganore said. By January 2012, The Michael J. Fox Foundation had invested more than $47 million in projects targeting alpha-synuclein.
"In my 20 years, if this finding proves to be correct, it is the single most important contribution that I have made in my career. It would rank up there with the 1997 discovery of the importance of alpha-synuclein," Maraganore said. "It is telling us, yes, this protein is at the heart of this disease. However, we don't understand its role well enough yet to safely move forward with treatment, and we need to explore a completely new possibility."
Berger, S. (4 Sep 2013). Chicago Tribune. Research casts doubt on Parkinson's disease treatment. articles.chicagotribune.com
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