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Combined Therapy with Idebenone and Deferiprone in Patients with Friedreich’s Ataxia

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Abstract

Iron chelators are a new therapeutical approach for patients with Friedreich’s ataxia, on the basis that oxidative cell damage that occurs in these patients is due to the increasing deposits of mitochondrial iron pools. The objective of the study was to evaluate the effects of the combined therapy of idebenone and low oral doses of deferiprone on the neurological signs and cardiac function parameters. This study was designed as a prospective open-label single-arm study. Twenty Friedreich’s ataxia patients were treated with idebenone (20 mg/kg/day) and deferiprone (20 mg/kg/day) for 11 months. Patients were evaluated before the start and throughout the study with the International Cooperative Ataxia Rating Scale (ICARS) scores, echocardiographic measurements and MRI (magnetic resonance imaging) techniques to asses brain iron deposits in the dentate nucleus. No significant differences were observed in total ICARS scores when comparing baseline status and the end of the study in the whole group of patients. Posture and gait scores increased significantly after 11 months of therapy (Wilcoxon’s test, p = 0.04) and kinetic function improved significantly (Wilcoxon’s test, p = 0.015). Echocardiography data showed a significant reduction of the interventricular septum thickness (Wilcoxon’s test, p = 0.04) and in the left ventricular mass index (Wilcoxon’s test, p = 0.038) after the start of the therapy. The MRI values in the dentate nucleus showed a statistically significant reduction (Wilcoxon’s test p = 0.007) between baseline conditions and after 11 months of the therapy. Combined therapy with idebenone and deferiprone in patients with FDRA indicates a stabilizing effect in neurologic dysfunctions due to an improvement in the kinetic functions, with a worsening of gait and posture scores. Heart hypertrophy parameters and iron deposits in dentate nucleus improved significantly. Combined therapy was well tolerated with mild side effects, apart from the risk of neutropenia and progressive reduction of plasma iron parameters.

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Acknowledgements

This study was supported by the Sant Joan de Déu Fundation, Hospital Sant Joan de Déu-University of Barcelona. Spain. We are indebted to the parents and patients that collaborated in this study and their general paediatricians. The CIBERER is an initiative of the ISCIII, MCIN, Spain.

Financial Disclosure

Dr. Artuch and Dr. Pineda received in 2009, from Santhera Pharmaceuticals Ltd., a grant for their studies with idebenone in patients with Friedreich’s ataxia.

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Authors and Affiliations

  1. Cardiology Department, Sant Joan de Déu Hospital and the University of Barcelona, 2, Passeig Sant Joan de Déu, 08950 Esplugues, Barcelona, Spain

    Daniel Velasco-Sánchez & Lorenzo Jiménez

  2. Sant Joan de Déu Foundation, 39-57, Calle Santa Rosa, 08950 Esplugues, Barcelona, Spain

    Daniel Velasco-Sánchez

  3. Neuropediatrics Department, Sant Joan de Déu Hospital, the University of Barcelona, and Center for Biomedical Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain

    Asuncion Aracil, Mar O’Callaghan & Mercedes Pineda

  4. Biochemistry Department, Sant Joan de Déu Hospital and CIBERER, Barcelona, Spain

    Raquel Montero, Maria Tondo & Rafael Artuch

  5. Pharmacy Department, Sant Joan de Déu Hospital and the University of Barcelona, Barcelona, Spain

    Ana Mas

  6. Radiology Department, Sant Joan de Déu Hospital and the University of Barcelona, Barcelona, Spain

    Antoni Capdevila & Josep Blanch

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  1. Daniel Velasco-Sánchez
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Correspondence to Daniel Velasco-Sánchez.

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Velasco-Sánchez, D., Aracil, A., Montero, R. et al. Combined Therapy with Idebenone and Deferiprone in Patients with Friedreich’s Ataxia. Cerebellum 10, 1–8 (2011). https://doi.org/10.1007/s12311-010-0212-7

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