Parkinson's patients with higher urate levels in their blood and CSF had slower functional decline

Individuals with Parkinson's disease who have higher levels of a metabolite called urate in their blood and in cerebrospinal fluid (CSF) have a slower rate of disease progression, according to a study funded by the National Institutes of Health. A clinical trial is under way to examine the safety and potential benefits of supplemental urate elevation for recently diagnosed Parkinson's patients who have low urate levels.

Investigators demonstrated the link with urate by mining a repository of clinical data and tissue samples collected from Parkinson's patients more than 20 years ago as part of a pioneering study called DATATOP, funded by NIH's National Institute of Neurological Disorders and Stroke (NINDS). The new study appears in Archives of Neurology. It was funded primarily by NINDS, with additional support from the Department of Defense and private organizations.

"This study speaks to the value of saving data and biospecimens from large clinical studies, and making them available to the research community to pursue new, unanticipated ideas," said Michael Schwarzschild, M.D., Ph.D., an associate professor of neurology at Massachusetts General Hospital in Boston, who lead the study together with Alberto Ascherio, M.D., Dr.PH, a professor of epidemiology and nutrition at the Harvard School of Public Health.

Experts emphasize there is no proof that elevating urate levels will help against Parkinson's disease, and that it should not be attempted outside of a clinical trial, where physicians can closely monitor possible benefits and risks, such as gout and heart disease.

Parkinson's disease attacks cells in the brain that regulate movement by releasing a chemical called dopamine. The loss of those cells leads to progressively disabling symptoms, including involuntary shaking, slow movement, stiffened muscle tone, and impaired balance. Levodopa, a precursor of dopamine, provides some relief from those symptoms but does not alter the disease course.

"Effective treatments for Parkinson's disease have been elusive. By taking a fresh look at the repository of clinical data and stored samples from the two-decade old DATATOP trial, this study has identified urate as a biomarker for the progression of the disease and suggests a potential new pathway for targeted therapy development," said Margaret Sutherland, Ph.D., a program director at NINDS.

Urate (or uric acid) is a product of the body's metabolism. Diets high in liver, seafood, and dried beans and peas tend to cause higher levels of urate in the blood, and are also associated with gout - a painful buildup of urate crystals in the joints. Urate is a natural antioxidant, and many studies have found that antioxidants slow the course of Parkinson's disease in animal models. Also, prior research from Dr. Ascherio's epidemiology group has shown that people who have gout or who consume foods associated with high urate have a lower incidence of Parkinson's disease.

Drs. Ascherio and Schwarzschild and their collaborators in the Parkinson Study Group are the first to examine whether urate levels are related to the course of Parkinson's disease. Last year, after mining data from another large clinical trial, they reported that high levels of urate in blood were associated with a slower disease course. The new study is an expansion of that work and the first time that investigators have looked for a connection between the course of Parkinson's and levels of urate in CSF, the fluid that fills spaces in the brain and spinal cord.

The DATATOP trial began in the late 1980s, and was designed to test whether vitamin E, the drug deprenyl (selegiline), or a combination of both could slow the course of early-stage Parkinson's disease. The trial enrolled 800 patients and followed them for two years. Deprenyl, which inhibits the breakdown of dopamine, was found to provide short-term relief from symptoms. Vitamin E showed no significant benefit.

As part of the DATATOP trial, samples of blood and CSF were acquired from more than 90 percent of the participants at enrollment. In the new study, the researchers analyzed whether blood and CSF urate levels were related to the course of Parkinson's by relying on blood measurements done at the time of the DATATOP trial and by taking new measurements from the 20-year-old, frozen samples of CSF.

Looking across all of the treatment groups in the study, the researchers found that patients with the highest urate levels in their blood and CSF had a slower functional decline as measured by their need for levodopa treatment. The results suggest that urate elevation might slow the course of Parkinson's in patients with early-stage disease and low urate levels.

Comments

  1. HARVEY  GROVE HARVEY GROVE United States says:

    Thank you for this article. I have a very unusual Parkinsons case. My Doc is the Chief of Neuro at a major Boston Medical Center and Medical school. He made the diagnosis about 3 years ago. I have had all the symptoms of PD at various times. From a walker, then to a cane, now neither. I had a period where I could not turn  over in bed. I've had episodes where I could not control my body and I would bend over from the waist while walking (all out of my control) and then  fall due to my center of gravity being so far outside the base. My voice has changed and then returned. This happens over and over at times with no pattern.I have developed a gait disorder that also comes and goes so that I walk like a drunken sailor on occaision. This also comes and goes.

    The funny thing about all of this is I have an elevated urea in my blood and take alopurinol for a very occaisional gout flare up. I have polycystic kidney disease and the PD has progressed extremely slowly as I was an electrologist who worked with very fine instruments that are as fine as a hair with no trouble. No tremor in my hands or elesewhere. I looked up PD in a very famous text book and I have had all the PD symptoms at one time or another. They come and go. My father had the flu in 1918 and developed PD. He died at age 88 with all the symptoms. I am 82 with some very serious disorders but my PD does not change to something more severe. I drive, walk, eat with no choking and lead a very normal life. My doc and I are working on this idea of urea having an effect on PD. He had never heard of it until I brought it up.He told me that I've had this for many years but most of it was subclinical until I fell from bending at the waist.  I'm not complaining about anything but I would like to help others if possible. Thank you for the info.

  2. HARVEY  GROVE HARVEY GROVE United States says:

    Pardon me. I made a serious error in the preceding comment but it can not be corrected. My doc did know of the urate cases, however, he sees mostly serious cases who are referred to him after they have been seen and treated by local docs and then sent to him for a consult. I happen to be the first case in a long time with so all the symptoms of PD except for the fact they are not all present at the same time. Plus I have a kidney disease that effects urate, consequently, he nevewr had achance towork with someone like me with all the kidney problems and gout with PD.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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