Improved Parkinsons disease motor score in a single-arm open-label trial of febuxostat and inosine.

Background: Cellular energetics play an important role in Parkinsons disease etiology, but no treatments directly address this deficiency. Our past research showed that treatment with febuxostat and inosine increased blood hypoxanthine and ATP in healthy adults, and a preliminary trial in 3 Parkinson's disease patients suggested some symptomatic improvements with no adverse effects. Methods: To examine the efficacy on symptoms and safety in a larger group of Parkinsons disease patients, we conducted a single-arm, open-label trial at 5 Japanese neurology clinics and enrolled thirty patients (n(males) = 11;n(females) = 19); 26 patients completed the study (n(males) = 10;n(females) = 16). Each patient was administered febuxostat 20 mg and inosine 500 mg twice-per-day (after breakfast and dinner) for 8 weeks. The primary endpoint was the difference of MDS-UPDRS Part III score immediately before and after 57 days of treatment. Results: Serum hypoxanthine concentrations were raised significantly after treatment (Pre = 11.4 mu M; Post = 38.1 mu M;P < .0001). MDS-UPDRS Part III score was significantly lower after treatment (Pre = 28.1 +/- 9.3; Post = 24.7 +/- 10.8; mean +/- SD;P = .0146). Sixteen adverse events occurred in 13/29 (44.8%) patients, including 1 serious adverse event (fracture of the second lumbar vertebra) that was considered not related to the treatment. Conclusions: The results of this study suggest that co-administration of febuxostat and inosine is relatively safe and effective for improving symptoms of Parkinsons disease patients. Further controlled trials need to be performed to confirm the symptomatic improvement and to examine the disease-modifying effect in long-term trials.