Promising Parkinson’s Finding Spurs New Clinical Study

University of Rochester to Help Lead Major Initiative by Michael J. Fox Foundation

April 15, 2008

The progression of Parkinson’s disease is slower in patients who have high blood levels of urate, a close chemical cousin of the molecule that causes gout, researchers have found. The finding could lead to a way to predict how a given patient with the disease will fare, and it opens the door to a new approach for treating or preventing the disease.

The findings were made public – posted online by the Archives of Neurology on April 14 – the same day that the Michael J. Fox Foundation announced a new study aimed at slowing the disease by continuing the research in people. The foundation is funding a $5.6 million study, the largest award in the foundation’s history, to investigate the potential of boosting urate levels to slow or stop the disease.

The project is being led by physicians at Harvard and Massachusetts General Hospital together with neurologists at the University of Rochester Medical Center.

Urate and its close chemical cousin, uric acid, are best known for causing painful conditions like gout and kidney stones when found at too-high levels. But Michael A. Schwarzschild, M.D., Ph.D., of Massachusetts General Hospital, and Alberto Ascherio, M.D. of the Harvard School of Public Health, together with Rochester colleagues found that urate, a powerful antioxidant that protects cells from damage, might protect patients against the effects of Parkinson’s disease.

To conduct their study, Schwarzschild and Ascherio turned to a large body of data collected by Rochester neurologists and their colleagues around the world in a Parkinson’s study conducted a few years ago. That study looked at the effects of an experimental compound known as CEP1347 in 804 people who had been recently diagnosed with Parkinson’s disease. The compound did not slow the disease.

But as often happens in medical research, what appeared to be a “failed” study ended up yielding crucial data.

Schwarzschild and Ascherio sifted through the extensive data from the study, including blood levels of urate taken at the beginning of the study, one month later, and then every three months for two years. Their analysis showed that participants with the highest levels of urate were half as likely as those with the lowest levels to progress to the point where they needed medication to treat their symptoms. Brain scans showed that participants with higher urate levels also lost the fewest dopamine-producing neurons, the type of brain cell affected by the disease.

“This is a great example of the phoenix rising from the ashes, if you will,” said neurologist Karl Kieburtz, M.D., professor of Neurology at the University of Rochester Medical Center. “The outcome of the initial study was a disappointment, as the compound did not slow the progression of the disease. But from that study comes a very promising lead that opens up a whole new area for investigation.”

Kieburtz is one of the leaders of the new study funded by the Michael J. Fox Foundation. The study will determine the safety of using inosine, a nutritional supplement known to raise urate levels, in patients. The study will begin later this year at several sites around the country and will include 90 people recently diagnosed with Parkinson’s disease but who do not yet need treatment. Until more is known, physicians caution Parkinson’s patients not to take inosine in an effort to slow the disease.

“It’s not yet clear how the levels of urate might be manipulated to benefit patients with Parkinson’s disease,” said Steven Schwid, M.D., professor of Neurology at the University of Rochester who was part of the urate and CEP1347 studies. “Well done clinical trials not only answer the main question of interest, but also provide an opportunity to examine issues that we may not have even thought about yet.”

Adds Schwarzschild: “Potential benefits of urate have to be tempered against the known risks of elevated urate levels, which include gout and kidney stones. From what we know now, urate elevation should only be attempted in the context of a closely monitored clinical trial, in which potential benefits and risks are carefully balanced.”

Schwarzschild is head of the new study. Also helping to lead the study are Kieburtz and Ascherio; the University of Rochester’s Clinical Trials Coordination Center, led by Kieburtz, will coordinate the study. The work is funded through the Michael J Fox Foundation’s LEAPS (Linked Efforts to Accelerate Parkinson’s Solutions) 2007 initiative. LEAPS 2007 was funded with a lead gift from the Edmond J. Safra Foundation, one of the most steadfast supporters of the Michael J. Fox Foundation since its inception.

The research described in the Archives of Neurology was supported by the National Institutes of Health and the American Federation for Aging Research. In addition to Schwarzschild, Ascherio and Schwid, authors include neurologist Ira Shoulson, M.D., biostatistician David Oakes, Ph.D., and programmer Arthur Watts, Ph.D., of the University of Rochester; Kenneth Marek, M.D., of the Institute for Neurodegenerative Disorders in New Haven, Conn., and Anthony Lang, M.D., of Toronto Western Hospital.

The initial study of CEP1347 that produced the crucial data for the new study was led by Shoulson and carried out by the Parkinson Study Group. The PSG, currently headed by Kieburtz, is a worldwide group of collaborating neurologists based at the University of Rochester Medical Center that studies new treatments for the disease. The University’s Clinical Trials Coordination Center has conducted more than 50 clinical trials involving more than 15,000 patients with conditions like Parkinson’s and Huntington’s diseases, forming an incredible database of knowledge about people with neurodegenerative disorders.

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