Setmelanotide for the treatment of severe early-childhood genetic obesity
Monogenic forms of early onset severe childhood obesity (ie, presenting before the age of 5 years) can occur in the context of pathogenic variants of single genes of large effect sizes, most of them encoding proteins which are involved in the central leptin-melanocortin signalling pathway. A deficiency in melanocortin-4 receptor (MC4R) signalling by single deficient proteins can be caused by rare biallelic variants in the genes encoding proopiomelanocortin (POMC), leptin receptor (LEPR), or proprotein convertase subtilisin/kexin type 1 (PCSK1), which encodes a protein that cleaves the precursor protein POMC into two separate ligands for MC4R: α-melanocyte stimulating hormone (α-MSH) and β-MSH.
