Oral Inosine Persistently Elevates Plasma Antioxidant Capacity in Early Parkinson’s Disease (S37.009)

OBJECTIVE: To investigate changes in total plasma antioxidant capacity after administration of oral inosine in early Parkinson’s disease (PD). BACKGROUND: Higher serum urate is associated with decreased incidence and slower progression of PD. Urate’s antioxidant activity is hypothesized to protect against neurodegeneration. The SURE-PD (Safety of URate Elevation in Parkinson’s Disease) study is a Phase II, randomized, double-blind, placebo-controlled trial of oral inosine to assess the safety of elevating serum urate in patients with early PD and serum urate <5.8 mg/dL. In the intervention groups, inosine dosage was administered to raise serum urate to 6.1-7 mg/dL (mild) or 7.1-8 mg/dL (moderate). DESIGN/METHODS: Total antioxidant capacity - assayed by ferric-reducing antioxidant power (FRAP) - was measured in plasma at baseline, after six months, and at end of treatment (average eighteen months) in placebo (n=23), mild (n=21) and moderate (n=24) groups. RESULTS: Baseline FRAP values were similar across all groups. At six months, FRAP was 29% higher among mild (1166μM) and 43% higher among moderate (1290 μM) group participants compared to placebo (903 μM) participants (p < 0.001 for each). The moderate group had higher FRAP levels compared to the mild group from six months to end of treatment (p = 0.025). FRAP values of mild and moderate group participants remained elevated at end of treatment (p < 0.001 for each vs. baseline). Change in FRAP from baseline correlated with change in serum urate (r = 0.86) and with change in UPDRS I-III total score among women (r = -0.44, p = 0.006) but not among men (p = 0.51). CONCLUSIONS: Treatment with oral inosine results in sustained, dose-dependent elevation of plasma antioxidant activity. The findings demonstrate an intended biological effect of potential therapeutic relevance and suggest that homeostatic mechanisms do not counteract the plasma antioxidant effects of urate elevation. Study Supported by: The Michael J. Fox Foundation Disclosure: Dr. Bhattacharyya has nothing to disclose. Dr. Bakshi has nothing to disclose. Dr. Logan has nothing to disclose. Dr. Ascherio has received personal compensation for activities with Merck & Co., Inc. as a speaker. Dr. Macklin has nothing to disclose. Dr. Schwarzschild has nothing to disclose.