Antioxidant treatment of patients with Friedreich ataxia: four-year follow-up.
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.


METHODS
Open-labeled pilot trial over 47 months.Patients Seventy-seven patients with clinical and genetically defined FRDA. Intervention A combined coenzyme Q(10) (400 mg/d) and vitamin E (2100 IU/d) therapy of 10 patients with FRDA over 47 months.


METHODS
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.


CONCLUSIONS
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.
Hart
Paul E
PE
University Department of Clinical Neurosciences, Royal Free and University College Medical School, London, England.
Lodi
Raffaele
R
Rajagopalan
Bheeshma
B
Bradley
Jane L
JL
Crilley
Jenifer G
JG
Turner
Christopher
C
Blamire
Andrew M
AM
Manners
David
D
Styles
Peter
P
Schapira
Anthony H V
AH
Cooper
J Mark
JM
D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage*; D002648:Child; D003067:Coenzymes; D004359:Drug Therapy, Combination; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D005500:Follow-Up Studies; D005621:Friedreich Ataxia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010865:Pilot Projects; D016896:Treatment Outcome; D014451:Ubiquinone / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D014810:Vitamin E / Q000008:administration & dosage*; D000096923:Frataxin
D000975:Antioxidants; D003067:Coenzymes; D033862:Iron-Binding Proteins; D014451:Ubiquinone; D014810:Vitamin E; D000096923:Frataxin; C024989:coenzyme Q10