Mechanistic insights on the effects of suramin, on the cardiomyopathy of the mdx mice.

Abstract

Duchenne Muscular Dystrophy (DMD) is a genetic disease characterized by the lack of dystrophin and progressive skeletal and cardiac muscles degeneration. In DMD and in the mdx mice model of DMD, heart and diaphragm are severely affected showing extensive fibrosis and loss of function. Cardiomyopathy is an increasing cause of death in DMD. However, while some drugs show positive effects in the function of the cardiac muscle, they may have no effect on cardiac fibrosis or on skeletal muscle dystrophy. Therefore, the study of new possibilities of pharmacological therapy is important.Previously, we demonstrated that suramin, an anti fibrotic agent used to treat some types of human cancer, was able to protect the dystrophic diaphragm and limb muscles of the mdx mice against myonecrosis (Taniguti et al., 2011). Further, we demonstrated that suramin improved the levels of b-dystroglycan, a key component of the dystrophin-glycoprotein complex (Taniguti et al., 2012, submitted). More recently, we demonstrated positive effects of suramin on mdx cardiomyopathy, by decreasing cardiac fibrosis and ameliorating mdx electrocardiography (Moreira et al., in preparation).In the present study, we aim to further evaluate the actions of suramin on the dystrophic cardiac muscle. First, we will verify whether suramin also affects b-dystroglycan levels. Second, we will evaluate the actions of suramin as a blocker of purinergic receptors, which are suggested to be involved in the cardiomyopathy related to other diseases.