Pilot trial of inosine to elevate urate levels in amyotrophic lateral sclerosis.

摘要: Objective To test the safety, tolerability, and urate-elevating capability of urate precursor inosine taken orally or by feeding tube in people with amyotrophic lateral sclerosis (ALS). Methods This was a pilot, open-label trial 25 participants ALS. Treatment duration 12 weeks. The dose titrated at pre-specified time points to elevate serum levels 7-8 mg/dL. Primary outcomes were safety (as assessed occurrence adverse events [AEs]) tolerability (defined as ability complete 12-week study on drug). Secondary included biomarkers oxidative stress damage. As an exploratory analysis, observed compared virtual control arm built using prediction algorithms estimate ALSFRS-R scores. Results Twenty-four out (96%) completed weeks drug treatment. One participant unable comply visits lost follow-up. Serum rose target 6 No serious AEs attributed no special concern, such urolithiasis gout, occurred. Selected damage had significant changes during period. Observed did not differ from baseline predictions. Interpretation Inosine appeared safe, well tolerated, effective raising These findings, together epidemiological observations preclinical data supporting neuroprotective role ALS models, provide rationale for larger clinical trials testing potential disease-modifying therapy