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Abstract
Objective To investigate whether women and men with Parkinson disease (PD) differ in their biochemical and clinical responses to long-term treatment with inosine.
Methods The Safety of Urate Elevation in Parkinson’s Disease (SURE-PD) trial enrolled 75 people with early PD and baseline serum urate below 6 mg/dL and randomized them to 3 double-blinded treatment arms: oral placebo or inosine titrated to produce mild (6.1–7.0 mg/dL) or moderate (7.1–8.0 mg/dL) serum urate elevation for up to 2 years. Parkinsonism, serum urate, and plasma antioxidant capacity were measured at baseline and repeatedly on treatment; CSF urate was assessed once, at 3 months. Here in secondary analyses results are stratified by sex.
Results Inosine produced an absolute increase in average serum urate from baseline that was 50% greater in women (3.0 mg/dL) than in men (2.0 mg/dL), consistent with expected lower baseline levels in women. Similarly, only among women was CSF urate significantly greater on mild or moderate inosine (+87% [p < 0.001] and +98% [p < 0.001], respectively) than on placebo (in contrast to men: +10% [p = 0.6] and +14% [p = 0.4], respectively). Women in the higher inosine dosing group showed a 7.0 Unified Parkinson’s Disease Rating Scale (UPDRS) points/year lower rate of decline vs placebo (p = 0.01). In women, slower rates of UPDRS change were associated with greater increases in serum urate (r = −0.52; p = 0.001), and with greater increases in plasma antioxidant capacity (r = −0.44; p = 0.006). No significant associations were observed in men.
Conclusions Inosine produced greater increases in serum and CSF urate in women compared to men in the SURE-PD trial, consistent with the study's design and with preliminary evidence for slower clinical decline in early PD among women treated with urate-elevating doses of inosine.
Clinicaltrials.gov identifier NCT00833690.
Classification of evidence This study provides Class II evidence that inosine produced greater urate elevation in women than men and may slow PD progression in women.
Glossary
- AE=
- adverse event;
- ANOVA=
- analysis of variance;
- CI=
- confidence interval;
- FRAP=
- ferric reducing antioxidant power;
- MAO-B=
- monoamine oxidase-B;
- PD=
- Parkinson disease;
- SAE=
- serious adverse event;
- SURE-PD=
- Safety of Urate Elevation in Parkinson’s Disease;
- UPDRS=
- Unified Parkinson’s Disease Rating Scale
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
SURE-PD coinvestigators are listed at links.lww.com/WNL/A963.
Editorial, page 611
Class of Evidence: NPub.org/coe
- Received November 10, 2018.
- Accepted in final form May 10, 2019.
- © 2019 American Academy of Neurology
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