Prospective epidemiological studies consistently indicate that Parkinson’s disease (PD) risk declines with increasing serum urate.

To determine whether serum urate, a purine metabolite and potent antioxidant, predicts prognosis in PD.

Prospective study among 804 subjects with early PD enrolled in the PRECEPT study, a clinical trial of the neuroprotectant potential of CEP-1347, conducted between April 2002 and August 2005 (average follow-up time 21.4 months).

The primary study endpoint was progression to clinical disability sufficient to warrant dopaminergic therapy. Cox proportional hazards models were used to estimate the hazard ratio (HR) of reaching endpoint according to quintiles of baseline serum urate, adjusting for gender, age and other potential covariates. Change in striatal uptake of [¹²³I]β-CIT, a marker for the presynaptic dopamine transporter, was assessed with linear regression for a subset of 399 subjects.

The adjusted HR of reaching endpoint declined with increasing baseline concentrations of urate; subjects in the top quintile reached the endpoint at only half the rate of subjects in the bottom quintile (HR=0.51; 95% CI: 0.37 to 0.72; p=0.0002). This association was markedly stronger in men (HR=0.39; 95% CI: 0.26 to 0.60; p<0.0001) than in women (HR=0.77; 95% CI: 0.39 to 1.50; p=0.4). The percent loss in striatal [¹²³I]β-CIT uptake also improved with increasing serum urate concentrations (overall p for trend=0.002; men, p=0.0008; women, p= 0.4).

These findings identify serum urate as the first molecular factor directly linked to the progression of typical PD and suggest that targeting urate or its determinants could be an effective disease modifying therapy in PD.