MC4 receptor antagonists: a potential treatment for cachexia

Cachexia (involuntary weight loss) is a devastating syndrome associated with many chronic diseases including cancer, and heart, lung, kidney and liver failure. There are currently no effective treatments capable of reversing the loss of lean body mass that is believed to be a major contributor to morbidity and mortality in these chronic diseases. Recent findings strongly indicate that blockade of central melanocortin signaling through the MC4 receptor subtype attenuates cachexia. This review summarizes the evidence supporting the role of MC4 receptors in cachexia, and highlights the progress achieved in the development of small-molecule MC4 antagonists, which have recently proved to be effective in animal models of cachexia. MC4 antagonists are an attractive therapeutic approach for cachexia that may ameliorate the loss of lean body mass in cachectic patients.