| Marked progress has been made over the past 15 years in defining the specific biochemical defects and underlying molecular mechanisms of oxidative phoshorylation defects, but limited information is currently available on the development and evaluation of effective treatment approaches. Metabolic therapies that have been reported to produce a positive effect include coenzyme Q10 (ubiquinone), other antioxidants (ascorbic acid, vitamin E), riboflavin, thiamine, niacin, vitamin K (phylloquinone and menadione), and carnitine. The goal of therapy is to increase mitochondrial ATP production, and to slow or arrest the progression of clinical symptoms. We have developed a method that utilizes circulating lymphocytes to examine the ability of the mitochondria to synthesize ATP when provided with selected substrates. In the present study, we have been able to demonstrate for the first time that an increase in ATP synthetic capacity in lymphocytes results from cofactor administration. To determine the effect of the individual components of the cofactor treatment on ATP synthesis we examined in vitro cofactor supplementation in control lymphocytes. A dose-dependent increase in ATP synthesis with CoQ10 incubation was demonstrated. Our data suggest that CoQ10 may have a beneficial effect in the treatment of OXPHOS disorders. The rapid and easy determination of ATP synthesis in lymphocytes from patients with mitochondrial disorders will allow designing of the most appropriate therapy on an individual basis. |
