Long-acting ghrelin analogue PEP-064 reverses cancer cachexia in C26 and LLC mouse models.

Cancer cachexia is a severe, involuntary weight loss syndrome affecting over 50% of terminal cancer patients, characterized by reduced food intake and metabolic reprogramming. It significantly impacts quality of life and survival, yet effective pharmacotherapies are lacking. Ghrelin, an orexigenic hormone, shows promise for improving energy balance and appetite, but its short half-life limits clinical utility. This study addresses this gap by developing PEP-064, a stabilized, long-acting ghrelin analogue designed to overcome these pharmacokinetic limitations.

Researchers evaluated PEP-064 in healthy CD-1 mice and two cancer cachexia models: C26 colon carcinoma and Lewis Lung Carcinoma (LLC). Healthy mice received repeated doses of PEP-064 (100, 300, and 1000 nmol/kg) for 7 days to assess dose-dependent effects on body weight and food intake. In cachexia models, PEP-064's ability to protect against tumor-free body weight, fat, and lean mass loss, and increase food intake, was measured. Pharmacokinetic profiling, whole brain c-Fos neuronal activity mapping, and growth hormone secretion were also assessed in healthy mice/rats.