Variant Gene Expression Linked to Motor Function Decline in Parkinson’s Disease

Results of a population study have shown that expression levels of the SNCA gene, which encodes alpha-synuclein protein, are directly related to the rate of decline of motor function in patients with Parkinson’s disease.

The SNCA gene is a well-known risk factor for Parkinson's disease, and higher levels of alpha-synuclein protein are associated with greater disease severity in familial cases of Parkinson's disease. Furthermore, postmortem studies have shown that expression varies with different SNCA genetic variants.

To study the role of SNCA variants in Parkinson’s disease investigators at the University of California, Los Angeles (USA observed a group of 233 Parkinson’s disease patients over a period averaging 5.1 years for motor symptom changes employing the Unified Parkinson’s Disease Rating Scale (UPDRS).

They reported in the May 15, 2012, online edition of the journal PLoS ONE that carriers of the SNCA variant Rep1 263bp had a four-fold higher risk of faster motor decline than patients carrying the rs356165 variant. An even stronger trend in progression toward motor decline was apparent in patients having both variants. While this was a relatively small study, with only 233 patients, the effects observed by the investigators were actually quite large.

“When doctors currently see Parkinson's disease patients, they cannot predict how rapidly their motor function will deteriorate - how quickly, for instance, they will reach a point when they need a wheelchair or other aids,” said senior author Dr. Jeff Bronstein, professor of neurology at the University of California, Los Angeles. “But if our results are confirmed, these gene variants can now identify patients who are likely to have faster progression.”

Being able to identify patients with the tendency for faster motor decline is expected to aid in the search for drugs to treat Parkinson’s disease. These individuals should respond to beneficial drugs earlier, thereby shortening the time required to evaluate drug performance.

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