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Four-Year Follow-up

Paul E. Hart, MRCP; Raffaele Lodi, MD; Bheeshma Rajagopalan, MD; Jane L. Bradley, PhD; Jenifer G. Crilley, MD; Christopher Turner, MRCP; Andrew M. Blamire, PhD; David Manners, DPhil; Peter Styles, DPhil; Anthony H. V. Schapira, MD, DSc; J. Mark Cooper, PhD

Arch Neurol. 2005;62:621-626.

Background  Decreased mitochondrial respiratory chain function and increased oxidative stress have been implicated in the pathogenesis of Friedreich ataxia (FRDA), raising the possibility that energy enhancement and antioxidant therapies may be an effective treatment.

Objective  To evaluate the long-term efficacy of a combined antioxidant and mitochondrial enhancement therapy on the bioenergetics and clinical course of FRDA.

Design  Open-labeled pilot trial over 47 months.

Patients  Seventy-seven patients with clinical and genetically defined FRDA.

Intervention  A combined coenzyme Q₁₀ (400 mg/d) and vitamin E (2100 IU/d) therapy of 10 patients with FRDA over 47 months.

Main Outcome Measures  Clinical assessment using echocardiography and the International Cooperative Ataxia Rating Scale and cardiac and skeletal muscle bioenergetics as assessed using phosphorus P 31 magnetic resonance spectroscopy.

Results  There was a significant improvement in cardiac and skeletal muscle bioenergetics that was maintained throughout the 47 months of therapy. Echocardiographic data revealed significantly increased fractional shortening at the 35- and 47-month time points. Comparison with cross-sectional data from 77 patients with FRDA indicated the changes in total International Cooperative Ataxia Rating Scale and kinetic scores over the trial period were better than predicted for 7 patients, but the posture and gait and hand dexterity scores progressed as predicted.

Conclusion  This therapy resulted in sustained improvement in mitochondrial energy synthesis that was associated with a slowing of the progression of certain clinical features and a significant improvement in cardiac function.

Author Affiliations: University Department of Clinical Neurosciences, Royal Free and University College Medical School, London (Drs Hart, Bradley, Turner, Schapira, and Cooper); Medical Research Council Biochemical and Clinical Magnetic Resonance Unit, Department of Biochemistry, University of Oxford and Oxford Radcliffe Hospital, Oxford (Drs Lodi, Rajagopalan, Crilley, Blamire, Manners, and Styles); and the Institute of Neurology, University College (Dr Schapira), London, England; and the Dipartimento di Medicina Clinica e Biotecnologia Applicata, Università di Bologna, Bologna, Italy (Dr Lodi).

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