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Michael A. Schwarzschild, MD, PhD; Steven R. Schwid, MD; Kenneth Marek, MD; Arthur Watts, MS; Anthony E. Lang, MD; David Oakes, PhD; Ira Shoulson, MD; Alberto Ascherio, MD; and the Parkinson Study Group PRECEPT Investigators

Arch Neurol. 2008;65(6):716-723. Published online April 14, 2008 (10.1001/archneur.2008.65.6.nct70003).

Objective  To determine whether concentration of serum urate, a purine metabolite and potent antioxidant that has been linked to a reduced risk of Parkinson disease (PD), predicts prognosis in PD.

Design  Prospective study.

Setting  The Parkinson Research Examination of CEP-1347 Trial (PRECEPT) study, which investigated the effects of a potential neuroprotectant on rates of PD progression, was conducted between April 2002 and August 2005 (average follow-up time 21.4 months).

Participants  Eight hundred four subjects with early PD enrolled in the PRECEPT study.

Main Outcome Measures  The primary study end point was progression to clinical disability sufficient to warrant dopaminergic therapy. Cox proportional hazards models were used to estimate the hazard ratio (HR) of reaching end point according to quintiles of baseline serum urate concentration, adjusting for sex, age, and other potential covariates. Change in striatal uptake of iodine I 123–labeled 2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane ([¹²³I]β-CIT), a marker for the presynaptic dopamine transporter, was assessed with linear regression for a subset of 399 subjects.

Results  The adjusted HR of reaching end point declined with increasing baseline concentrations of urate; subjects in the top quintile reached the end point at only half the rate of subjects in the bottom quintile (HR, 0.51; 95% confidence interval [CI], 0.37-0.72; P for trend < .001). This association was markedly stronger in men (HR, 0.39; 95% CI, 0.26-0.60; P for trend < .001) than in women (HR, 0.77; 95% CI, 0.39-1.50; P for trend = .33). The percentage of loss in striatal [¹²³I]β-CIT uptake also improved with increasing serum urate concentrations (overall P for trend = .002; men, P = .001; women, P = .43).

Conclusions  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.

Trial Registration  clinicaltrials.gov Identifier: NCT00040404.

Author Affiliations: MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital (Dr Schwarzschild), and Departments of Nutrition and Epidemiology, Harvard School of Public Health, and Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston (Dr Ascherio); Departments of Neurology and Biostatistics, University of Rochester, Rochester, New York (Drs Schwid, Oakes, and Shoulson and Mr Watts); Institute for Neurodegenerative Disorders, New Haven, Connecticut (Dr Marek); and Toronto Western Hospital, Toronto, Ontario, Canada (Dr Lang).

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