title: Triple therapy with darbepoetin alfa, idebenone, and riboflavin in Friedreich's ataxia: an open-label trial.
abstract: 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 ≥400 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 μg 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.
authors.affiliation: Reference Unit of Hereditary Ataxias and Paraplegias, Department of Neurology, IdiPAZ, Hospital Universitario La Paz, 28046, Madrid, Spain. jarpag@ctv.es
authors.forename: Javier
authors.initials: J
authors.lastname: Arpa
authors.forename: Irene
authors.initials: I
authors.lastname: Sanz-Gallego
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Rodríguez-de-Rivera
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Domínguez-Melcón
authors.forename: Daniel
authors.initials: D
authors.lastname: Prefasi
authors.forename: Javier
authors.initials: J
authors.lastname: Oliva-Navarro
authors.forename: Mar
authors.initials: M
authors.lastname: Moreno-Yangüela
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Pascual-Pascual
mesh_terms: D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D000068256:Darbepoetin alfa; D004359:Drug Therapy, Combination / Q000379:methods; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005621:Friedreich Ataxia / Q000175:diagnosis / Q000188:drug therapy*; D006397:Hematinics / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012256:Riboflavin / Q000008:administration & dosage / Q000627:therapeutic use*; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000975:Antioxidants; D006397:Hematinics; D004921:Erythropoietin; D014451:Ubiquinone; D000068256:Darbepoetin alfa; C036619:idebenone; D012256:Riboflavin