Triple Therapy with Darbepoetin Alfa, Idebenone, and Riboflavin in Friedreich's Ataxia: an Open-Label Trial

Minimal objective evidence exists regarding management of Friedreich's ataxia (FRDA). Antioxidant and recombinant human erythropoietin therapies have been considered potential treatments to slow progression of FRDA in a small number of studies. The primary objective of the current study was to test the efficacy, safety, and tolerability of triple therapy-darbepoetin alfa, idebenone, and riboflavin-in FRDA in a clinical pilot study. Patients included in this study were nine females, 16 to 45 years of age (average 28 +/- 8), diagnosed with FRDA with confirmed GAA repeat expansion mutations in the FXN gene and a GAA repeat a parts per thousand yen400 on the shorter allele. Patients had a baseline score between 8 and 28.5 (average 20.7 +/- 8.3) on the scale for the assessment and rating of ataxia and 94.3 +/- 27.2 g/m(2) in left ventricular mass index (LVMI). Patients had been treated with triple therapy with 150 mu g darbepoetin alfa every 2 or 3 weeks, 10-20 mg/kg/day idebenone, and 10-15 mg/kg/day riboflavin for 32 +/- 19.4 months (range of 8-56 months). Triple therapy was tolerated. Although not statistically significant, improvement of ataxia was observed during the first six 4-month periods of the study. Furthermore, a small decrease in disease progression during the first 2 years of treatment was observed. Long-term statistically nonsignificant improvement of LVMI and stability of the echocardiographic parameters could be considered. Triple therapy may slow disease progression of FRDA.