Mayo Clinic Research Provides Key to Parkinson's Disease Prevention

Friday, February 27, 2004

ROCHESTER, Minn. — Mayo Clinic researchers and collaborators worldwide have confirmed the important role of a gene variant in reducing risk for Parkinson's disease.

Demetrius Maraganore, M.D., Mayo Clinic neurologist, coordinated a large, international study that convincingly shows people that inherit a variant form "S18Y" of the ubiquitin carboxy-terminal hydrolase L1 (UCHL1) gene are at reduced risk for Parkinson's disease. The findings will be published in the February issue of Annals of Neurology, http://www3.interscience.wiley.com/cgi-bin/jhome/76507645.

According to Dr. Maraganore, this study supports the development of new drugs targeting the effects of this gene variant as a means of preventing Parkinson's disease and its progression.

"This is an important clue to treatment that might be developed against Parkinson's disease," he says. "Our research suggests that developing treatments that imitate the effects of this gene variant would be protective against Parkinson's disease."

According to Dr. Maraganore, if such a drug were developed, it might slow progression in patients who already have Parkinson's disease. It might also prevent the disease altogether in people at high risk for Parkinson's disease, such as members of a family with a gene mutation predisposing them to Parkinson's.

"The immediate beneficiaries would be those with Parkinson's disease," he says. "As we develope better screening, it would also help others at risk." Dr. Maraganore indicates, however, that it is currently difficult to identify those at high risk for Parkinson's.

Dr. Maraganore explains that the S18Y gene variant may protect against Parkinson's disease by making UCHL1 proteins that are less sticky. Sticky UCHL1 protein is less effective in clearing damaged proteins, including alpha synuclein. Accumulations of alpha synuclein have been shown to play a major role in the cause of Parkinson's disease. Accordingly, the aim of new drug development may be to discover compounds that make the UCHL1 protein less sticky. This will favor the elimination of the toxic protein alpha synuclein and thus protect against Parkinson's disease.

Study Details

The S18Y variant of the UCHL1 was discovered and purported to be a possible protector against Parkinson's in 1998. Dr. Maraganore and colleagues believed the results of the 1998 study to be plausible and decided to investigate whether a larger study pooling all the data from studies on UCHL1 worldwide would confirm the finding.

Dr. Maraganore recruited investigators from all 11 published studies on UCHL1 and Parkinson's to participate in this collaborative analysis. The pooled study included 1,970 Parkinson's disease patients and 2,224 controls.

The investigators found a statistically significant inverse association of the S18Y variant with Parkinson's disease: where S18Y was present, there was a reduced risk of Parkinson's development. This was seen even more strongly in younger patients.

Lisa Copeland
507-284-5005 (days)
507-284-2511 (evenings)
e-mail: newsbureau@mayo.edu

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