Repurposing of Glatiramer Acetate to Treat Heart Diseases

Abstract Myocardial injury may ultimately lead to adverse ventricular remodeling and development of heart failure (HF), which is a major cause of morbidity and mortality worldwide. Given the slow pace and substantial costs of developing new therapeutics, drug repurposing is an attractive alternative. Studies of many organs, including the heart, highlight the importance of the immune system in modulating injury and repair outcomes. Glatiramer-acetate (GA) is an immunomodulatory drug prescribed for patients with multiple sclerosis. Here we report that short-term GA treatment improves cardiac function and reduces scar area in a mouse model of acute myocardial infarction, as well as in a rat model of ischemic HF. We provide both in vivo and in vitro mechanistic evidence indicating that in addition to its immunomodulatory functions, GA exerts beneficial pleiotropic effects, including cardiomyocyte protection and enhanced angiogenesis, mediated partially by extracellular vesicles carrying a pro-reparative cargo. Finally, as GA is a widely used drug with established efficacy and safety history, we conducted a small, prospective, randomized trial to determine its effect on patients admitted to the hospital with acute decompensated HF (ADHF). Strikingly, a short-term add-on administration of GA, resulted in marked reduction in the cytokine surge and NT-proBNP levels, both associated with acute HF exacerbations. Overall, these findings demonstrate the efficacy of GA in attenuating acute myocardial injury and modulating the inflammatory process in animal models and humans and highlight the potential of GA as a future therapy for a myriad of heart diseases. One Sentence Summary Glatiramer acetate promotes reparative processes in rodent models of cardiac injury and reduces the inflammatory process in ADHF patients.