Development of a Cancer Cachexia Therapeutic

Gruber Kenneth A Cachexia anorexia syndrome is a life threatening aspect to many diseases in particular many forms of cancer or therapies for cancer The obvious symptoms of this disease include lack of appetite and a loss of lean body mass disproportionate to the reduction in caloric intake However the less obvious effects of cachexia include multi organ failure due to high metabolic rate induced apoptosis programmed cell death The economic costs of cachexia are huge The National Cancer Institute estimates that up to of cancer deaths are directly due to cachexia and it is likely a factor in a significant percent of other cancer fatalities Cachexia is a component in the pathology of many other diseases Hyperactivity of the central melanocortin MC system appears to be a common factor in most if not all forms of cachexia We designed and synthesized a MC drug like peptide TCMCB using a new platform technology that makes peptides into therapeutic agents with an extended in vivo half life TCMCB produced a reversal of cachexia in an aggressive experimental cancer model restoring food intake and lean body mass The ability of TCMCB to enhance weight gain has been confirmed in large animal models Preliminary safety testing has shown that the drug is relatively free of cardiovascular blood chemistry or hematological side effects The goals of this application are to perform the required preclinical experiments to establish the relative safety and efficacy of our anticachexia therapeutic and define its interactions with cellular transport systems Delineating the transport system s for TCMCB will allow a determination of its potential interaction with other clinically relevant drugs The overall objective of these experiments is the submission of an Investigative New Drug application to the FDA for an anticachexia drug a required step before Phased Clinical Trials Preventing or reversing cachexia has the potential to enhance the efficacy of current and future anticancer agents as well as be an important therapeutic component in the treatment of many other life threatening diseases Gruber Kenneth A Melanocortins MCs are naturally substances that have potential use as therapeutic agents in cachexia a condition of reduced appetite with enhanced metabolic rate We developed orally anti cachexia MC drugs and confirmed their safety and efficacy in small animal trials The project is now proceeding into the formal stages of FDA review