Modelling GM1 treatment in Experimental Chagas´ Disease

S. COSSY ISASI; M. RODRÍGUEZ; L. MARTÍNEZ; M. CORDERO; S. LOPRESTI; C.A. CONDAT; G.J. SIBONA

Los Cocos, Córdoba

Congreso; XXXVIII Reunión Anual de la Sociedad Argentina de Biofísica; 2009

Sociedad Argentina de Biofísica

Being one of the world´s neglected diseases, Chagas has neither a vaccine nor a satisfactory therapy. Treatment of murine models of the acute infection with the ganglioside GM1 has shown a strikingly nonlinear effect, leading to a strong decrease in parasite load at low doses but reverting to a load increase at high doses. Cardiocyte destruction concomitant with the disease is also significantly reduced by a moderate application of GM1. A mathematical model for the interaction between the parasite and the immune system is shown to explain these effects and is used to predict an optimal dosage that maximizes parasite removal with minimal cardiocyte destruction.  In murine models of the chronic disease, GM1 improved electrocardiographic records in mice with prolonged QT interval. Long QR syndrome (LQTS) is associated with delayed cardiac repolarization. Acquired LQTS most often results from administration of structurally diverse drugs that can block cardiac K+ channels, in particular channels carrying the rapid delayed rectifier current, IKr. When chronic mice (with arrhytmia and prolonged QT) were given one injection of GM1 and monitored one month later, approximately 30% contraction of prolonged QT was observed.  Since ganglioside GM1 regulates Na+/K+ ATPase in cultured neurons and muscle cells, and since QT interval reflects potassium repolarizing current, it seems possible that this mechanism underlies mice improvement. Since parasitemia is undetectable in chronic disease, modeling strategy shifts from population competition to models of molecular interactions.