EVALUATION OF NEW, CLINICALLY-SAFE NITRIC OXIDE-RELEASING DRUGS WITH ANTI-INFLAMMATORY PROPERTIES AS THERAPEUTIC AGENTS FOR MUSCULAR DISTROPHY

A resolutive therapy for the Duchenne Muscular Dystrophy is not yet available. The use of steroids, to control inflammation and slow-down the disease, causes severe side effects with poor clinical benefits. The Objective of the study is to develop a new pharmacological therapy of muscular dystrophies, using a new class of drugs (NCX-compounds) that can be delivered orally and combine anti-inflammatory actions with the properties of nitric oxide. The anti-inflammatory actions of these drugs are indeed potent, yet with moderate, if any side effects. Nitric oxide is a cellular messenger that exerts many positive effects on muscle sustaining its regeneration, metabolism and resistance to exercise and mechanical stress. In preliminary experiments we found that the NCX-compounds exert significant beneficial effects in a mouse model of dystrophy, the alpha-sarcoglycan null mouse. This preliminary evidence also suggests that these drugs may be usefully combined with cell therapy to enhance its therapeutic potential. The study we are proposing will test on a long-term period the efficacy of NCX-compounds, alone or combined with stem cells, to ameliorate the dystrophic phenotype of the alpha-sarcoglycan null mice. We will carry out morphological and biochemical analyses of muscles, and functional tests on the animals. Anticipated output: Identification of an experimental therapy with clinical-grade drugs that can path the way to studies in larger animals and, possibly, early entry studies in humans. Improvement of stem cell therapy with the ultimate goal of making it successful in humans.