Combined therapy with idebenone and deferiprone in patients with Friedreich's ataxia.
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.
Velasco-Sánchez
Daniel
D
Cardiology Department, Sant Joan de Déu Hospital, University of Barcelona, Esplugues, Spain. daniel.velasco.sanchez@gmail.com
Aracil
Asuncion
A
Montero
Raquel
R
Mas
Ana
A
Jiménez
Lorenzo
L
O'Callaghan
Mar
M
Tondo
Maria
M
Capdevila
Antoni
A
Blanch
Josep
J
Artuch
Rafael
R
Pineda
Mercedes
M
D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000009:adverse effects / Q000627:therapeutic use*; D001772:Blood Cell Count; D001923:Brain Chemistry / Q000187:drug effects; D002648:Child; D000077543:Deferiprone; D004359:Drug Therapy, Combination; D004401:Dysarthria / Q000209:etiology / Q000503:physiopathology; D005260:Female; D005621:Friedreich Ataxia / Q000000981:diagnostic imaging / Q000188:drug therapy*; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000503:physiopathology; D006334:Heart Function Tests; D006801:Humans; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D009460:Neurologic Examination; D009801:Oculomotor Muscles / Q000503:physiopathology; D011446:Prospective Studies; D011728:Pyridones / Q000009:adverse effects / Q000627:therapeutic use*; D013064:Speech Disorders / Q000209:etiology / Q000503:physiopathology; D014451:Ubiquinone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014463:Ultrasonography; D055815:Young Adult
D000975:Antioxidants; D007502:Iron Chelating Agents; D011728:Pyridones; D014451:Ubiquinone; D000077543:Deferiprone; D007501:Iron; C036619:idebenone