Melanocortin interventions in cachexia: how soon from bench to bedside?

Abstract

Cachexia is a condition of anorexia and wasting that accompanies many diseases including cancer, heart failure, and renal failure. One key center that is probably involved in the propagation of symptoms of cachexia is the melanocortin system in the hypothalamus and brainstem. This review focuses on cachexia treatment interventions that act via melanocortin antagonism, by direct or indirect means. Recent reports include a description of the physiology of the melanocortin system and its responsiveness to inflammatory cytokines. Regarding treatment potential, multiple reports describe the effectiveness of small molecule antagonists of the melanocortin-4 receptor in animal models of cachexia. These melanocortin antagonists, given by peripheral injection, improve food intake and lean body mass retention in the setting of cancer and renal failure. Additional reports provide evidence of melanocortin antagonism following treatment of cachexia using ghrelin and eicosonoic acid. Cachexia is a serious condition that accompanies various disease states and currently does not have effective treatments. The melanocortin system may play a direct role in producing symptoms of cachexia, making antagonism of this system a logical objective for ameliorating these symptoms. Thus far, however, no data on human application have been published.