Potential predictor of fast PD progression identified

Jun 14 2012

By Lauretta Ihonor

The identification of genetic variants of the α-synuclein (SNCA) gene may help to predict which individuals with idiopathic Parkinson's disease (PD) are likely to experience fast progression of motor symptoms, according to findings from a US-based genetic study.

Motor symptom severity is positively associated with mortality risk among PD patients and this association is independent of age and PD duration, say Beate Ritz (University of California, Los Angeles) and team.

They therefore suggest that "identifying genetic predictors of faster motor decline is critical to pinpointing biological mechanisms as targets for therapies and identifying patients who will most benefit from early interventions."

The SNCA protein is a major component of the Lewy bodies known to play a role in the pathogenesis of PD, explaining the association between SNCA variations and disease progression found in this study.

As reported in the open-access journal PLoS One, the team assessed SNCA genotypes of 233 California-based PD patients. The progression of motor symptoms, such as tremor and rigidity, were also observed in the group over a mean period of 5 years.

Changes in motor symptoms were measured using the Unified Parkinson's Disease Rating Scale (UPDRS). Fast motor symptom decline was defined as an annual UPDRS motor score fall of at least 5 points.

Ritz et al report that carriers of the REP1 263bp SNCA promoter variant had a 4.03-fold higher risk for fast motor symptom decline than PD patients without this variant.

Another variant, rs356165, was associated with a 1.66-fold increase in risk for fast motor symptom decline compared with noncarriers of this variant.

The authors say that "replication of our results in similarly well-characterized population-based incidence PD cohorts that have been longitudinally followed is still needed."

Nonetheless, they conclude that the findings from the current study suggest that "SNCA and related pathogenic pathways have great promise as potential disease modifying and therapeutic targets."

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