Serum urate as a predictor of clinical and radiographic progression in Parkinson disease
Michael A Schwarzschild, Steven R Schwid, Kenneth Marek, Arthur Watts, Anthony E Lang, David Oakes, Ira Shoulson, Alberto Ascherio, Parkinson Study Group PRECEPT Investigators, Christopher Hyson, Emily Gorbold, Alice Rudolph, Karl Kieburtz, Stanley Fahn, Lisa Gauger, Christopher Goetz, John Seibyl, Misser Forrest, John Ondrasik, Rajeev Kumar, Mandar Jog, Cheryl Horn, Kathleen Shannon, Maureen Leehey, Teresa Derian, David Grimes, Melodie Mortensen, Paul Tuite, Neal Hermanowicz, Shari Niswonger, Roger Kurlan, Irenita Gardiner, Janis Miyasaki, Lisa Johnston, James Tetrud, Joseph Friedman, Hubert Fernandez, Robert Rodnitzky, Judith Dobson, Virgilio Evidente, Marlene Lind, Pamela Andrews, Michel Panisset, Brad Racette, Patricia Deppen, Joseph Jankovic, Christine Hunter, Eric Molho, Stewart Factor, Joanne Wojcieszek, Burton Scott, Thyagarajan Subramanian, Ruth Kolb, Andrew Siderowf, Robert Hauser, Joseph Savitt, Melissa Gerstenhaber, Alok Sahay, Maureen Gartner, Margaret Turk, Jean Rivest, Frederick Wooten, Michael Schwarzschild, Marsha Tennis, Kapil Sethi, Lisa Hatch, Ronald Pfeiffer, Brenda Pfeiffer, Andrew Feigin, Tanya Simuni, Karen Williams, Lawrence Elmer, Antonelle deMarcaida, Sheila Thurlow, Sylvain Chouinard, Hubert Poiffaut, Holly Shill, Mark Stacy, Richard Zweig, Rhonda Feldt, Cheryl Waters, Rajesh Pahwa, Amy Parsons, Jennifer Hui, Allan Wu, Richard Camicioli, Pamela King, Arif Dalvi, Un Jung Kang, Stephen Reich, Lisa Shulman, Margery Mark, Ali Rajput, David Song, John M Bertoni, Carolyn Peterson, Karen Blindauer, Jeanine Petit, Bala Manyam, Oksana Suchowersky, Lewis Sudarsky, Daniel Tarsy, Mark Forrest Gordon, Alessandro DiRocco, Amy Andrzejewski, Nestor Galvez-Jimenez, Sami Harik, Samer Tabbal, Michael A Schwarzschild, Steven R Schwid, Kenneth Marek, Arthur Watts, Anthony E Lang, David Oakes, Ira Shoulson, Alberto Ascherio, Parkinson Study Group PRECEPT Investigators, Christopher Hyson, Emily Gorbold, Alice Rudolph, Karl Kieburtz, Stanley Fahn, Lisa Gauger, Christopher Goetz, John Seibyl, Misser Forrest, John Ondrasik, Rajeev Kumar, Mandar Jog, Cheryl Horn, Kathleen Shannon, Maureen Leehey, Teresa Derian, David Grimes, Melodie Mortensen, Paul Tuite, Neal Hermanowicz, Shari Niswonger, Roger Kurlan, Irenita Gardiner, Janis Miyasaki, Lisa Johnston, James Tetrud, Joseph Friedman, Hubert Fernandez, Robert Rodnitzky, Judith Dobson, Virgilio Evidente, Marlene Lind, Pamela Andrews, Michel Panisset, Brad Racette, Patricia Deppen, Joseph Jankovic, Christine Hunter, Eric Molho, Stewart Factor, Joanne Wojcieszek, Burton Scott, Thyagarajan Subramanian, Ruth Kolb, Andrew Siderowf, Robert Hauser, Joseph Savitt, Melissa Gerstenhaber, Alok Sahay, Maureen Gartner, Margaret Turk, Jean Rivest, Frederick Wooten, Michael Schwarzschild, Marsha Tennis, Kapil Sethi, Lisa Hatch, Ronald Pfeiffer, Brenda Pfeiffer, Andrew Feigin, Tanya Simuni, Karen Williams, Lawrence Elmer, Antonelle deMarcaida, Sheila Thurlow, Sylvain Chouinard, Hubert Poiffaut, Holly Shill, Mark Stacy, Richard Zweig, Rhonda Feldt, Cheryl Waters, Rajesh Pahwa, Amy Parsons, Jennifer Hui, Allan Wu, Richard Camicioli, Pamela King, Arif Dalvi, Un Jung Kang, Stephen Reich, Lisa Shulman, Margery Mark, Ali Rajput, David Song, John M Bertoni, Carolyn Peterson, Karen Blindauer, Jeanine Petit, Bala Manyam, Oksana Suchowersky, Lewis Sudarsky, Daniel Tarsy, Mark Forrest Gordon, Alessandro DiRocco, Amy Andrzejewski, Nestor Galvez-Jimenez, Sami Harik, Samer Tabbal
Abstract
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 ([(123)I]beta-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 [(123)I]beta-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.
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Source: PubMed