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

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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/m2 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.

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Acknowledgments

Statistical analyses were independently conducted by a statistician, Rosario Madero. Correction of the English manuscript was performed by Proof-reading-service.com. Dr Arpa has received grant funding for other projects from the Agencia Pedro Laín Entralgo (Madrid, Spain) and the Spanish Ministry of Health.

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Authors and Affiliations

  1. Reference Unit of Hereditary Ataxias and Paraplegias, Department of Neurology, IdiPAZ, Hospital Universitario La Paz, 28046, Madrid, Spain

    Javier Arpa, Irene Sanz-Gallego, Francisco J. Rodríguez-de-Rivera, Daniel Prefasi & Javier Oliva-Navarro

  2. Reference Unit of Hereditary Ataxias and Paraplegias, Department of Cardiology, IdiPAZ, Hospital Universitario La Paz, Madrid, Spain

    Francisco J. Domínguez-Melcón & Mar Moreno-Yangüela

  3. Reference Unit of Hereditary Ataxias and Paraplegias, Department of Neuropediatry, IdiPAZ, Hospital Universitario La Paz, Madrid, Spain

    Samuel I. Pascual-Pascual

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  1. Javier Arpa
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Correspondence to Javier Arpa.

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Arpa, J., Sanz-Gallego, I., Rodríguez-de-Rivera, F.J. et al. Triple Therapy with Darbepoetin Alfa, Idebenone, and Riboflavin in Friedreich’s Ataxia: an Open-Label Trial. Cerebellum 12, 713–720 (2013). https://doi.org/10.1007/s12311-013-0482-y

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  • DOI: https://doi.org/10.1007/s12311-013-0482-y

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