Parkinson disease progresses more slowly in patients who have higher levels of urate, a chemical that at very high level is associated with gout, scientists have found. While it’s unknown whether the high levels actually somehow protect patients or simply serve as a marker of protection, the finding supports the idea that patients and doctors may one day be able to better predict the course of the illness.
The study, led by scientists at Massachusetts General Hospital and the Harvard School of Public Health and including physicians at the University of Rochester Medical Center, was published online in the Archives of Neurology.
The new findings are based on biological samples, primarily blood and cerebrospinal fluid, collected from people with Parkinson disease who participated in a landmark study known as DATATOP, which was conducted two decades ago.
DATATOP, conceived and led by Rochester neurologist Ira Shoulson, M.D., is best known for shifting the landscape of neurology clinical research. Shoulson convinced dozens of investigators around the world to work together, pooling their resources to ask questions about potential new treatments for the disease — big questions that could be answered only with participation by hundreds of people with the disease.
Beginning in 1987, Shoulson and colleagues studied 800 people with Parkinson disease, looking at whether the drug deprenyl (selegiline), vitamin E, or a combination might slow the progression of the disease. The answer was a definitive “no” for vitamin E, while deprenyl provided patients with some relief.
But the scale and scope of the study proved to be useful beyond the specific questions it was designed to answer. The mountain of information collected on the 800 participants over eight years provided one of the great repositories of data about Parkinson disease ever assembled: thousands of blood, urine, and cerebrospinal fluid samples, as well as notes from more than 16,000 physical examinations of patients by doctors and nurses.
The data was central to the new study, which was led by Michael A. Schwarzschild, M.D., Ph.D., of Massachusetts General Hospital, and Alberto Ascherio, M.D. of the Harvard School of Public Health, who have been studying a possible role for urate in protecting patients against the effects of Parkinson disease. They found that the disease progressed more slowly in participants with the highest levels of urate than in people with the lowest levels.
The results mirror those of a study the same team published last year, when they studied data from another previous study, also led by Shoulson, which had looked at the effects of an experimental compound in 806 people who had been recently diagnosed with Parkinson disease. While the compound did not slow the disease, the study itself yielded another mountain of critical data.
With data from two previous studies proving so useful, Shoulson is working on ways to make current studies even more useful down the road. With funding from the National Institute of Neurological Disorders and Stroke, he is continuing to follow 537 of the original 806 people involved in one of the previous studies, monitoring the progression of their disease as well as obtaining blood and tissue samples for further investigation.
“This group comprises the largest living laboratory in the world for the study of the progression of Parkinson disease,” said Shoulson.
Shoulson hopes to grow the size of the group by adding participants from other studies to create one large cohort of 1,200 people with Parkinson disease who will be studied closely for five years. Doctors will track the health of participants and will make frequent measurements of several biomarkers, including certain blood proteins and genetic mutations that might affect the course of the disease.
“Why put together a large clinical trial to look at one question, then dissolve the entire structure and start all over again?” asked Shoulson. “Instead, we are taking full advantage of what has been accomplished previously. We are putting to better use the resources, efforts and time not only of scientists but also of the hundreds of patients with Parkinson disease who have been so generous to take part in our studies. Making the most of these resources to improve the lives of patients is what the clinical research enterprise is all about.”
Meanwhile, the team led by Schwarzschild is conducting a new study funded by the Michael J. Fox Foundation to determine the safety of using inosine, a nutritional supplement known to raise urate levels, in patients. Until more is known, physicians caution Parkinson patients not to take inosine in an effort to slow the disease. The study is being coordinated by Rochester’s Clinical Trials Coordination Center.
All of these studies are being coordinated by the Parkinson Study Group, a worldwide group of collaborating neurologists founded by Shoulson and 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 and Huntington diseases, forming a formidable database of knowledge about people with neurodegenerative disorders.
Rochester authors of the latest paper include Shoulson; Karl Kieburtz, M.D.; Alice Rudolph, Ph.D.; David Oakes, Ph.D.; Arthur Watts; Shirley Eberly; and the late Steven Schwid, M.D. The study published in the Archives of Neurology was funded by the National Institute of Neurological Disorders and Stroke, the U.S. Department of Defense, and several private organizations.
