Courting Melanocortin

A pair of genome-wide association studies makes the case that mutations near the melanocortin 4 receptor locus are common determinantsof obesity in humans.^1,2 The studies may encourage discovery efforts in the obesity space by at least two biotech companies, Palatin Technologies Inc. and Action Pharma A/S, that focus on targeting melanocortin receptors. However, the specific mutations that underlie the high-risk locus have not yet been identified, leaving the therapeutic path still unmapped.

The G protein-coupled receptor melanocortin 4 receptor (MC4R) is found throughout the nervous system, where it integrates signals from a variety of peptide hormones to regulate feeding behavior and libido. In mice, disruption of MC4R causes severe obesity and metabolic syndrome, whereas humans with rare loss-of-function mutations have hereditary hyperphagia (a propensity to overeat) and early-onset obesity.³...