Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders

Substantial evidence indicates that bioenergetic dysfunction plays either a primary or secondary role in the pathophysiology of cell death in neurodeg enerative and neuromuscular disorders, and even in normal aging. Agents tha t ameliorate bioenergetic defects may therefore be useful in therapy. Creat ine, which increases muscle and brain phosphocreatine concentrations, and m ay inhibit the activation of the mitochondrial permeability transition, pro tects against neuronal degeneration in transgenic murine models of amyotrop hic lateral sclerosis and Huntington's disease and in chemically mediated n eurotoxicity. Initial studies of creatine use in humans appear promising; h owever, further long-term, well-designed trials are needed. Coenzyme Q(10), Gingko biloba, nicotinamide, riboflavin, carnitine, lipoic acid, and dichl oroacetate are other agents which may have beneficial effects on energy met abolism, but the preclinical and clinical evidence for efficacy in neurolog ical diseases remains limited. These compounds are widely used as dietary s upplements; however, they must be subjected to rigorous evaluation through randomized, double-blinded trials to establish efficacy, cost-effectiveness and safety in neurological disorders.