hrp0084fc12.4 | Obesity - Clinical | ESPE2015

RM-493, a Melanocortin-4 Receptor (MC4R) Agonist, is Being Therapeutically Evaluated in Patients with Deficiencies in the Leptin – Proopiomelanocortin (POMC) – MC4R Hypothalamic Pathway, Including Prader–Willi Syndrome (PWS)

Kuhnen Peter , Krude Heiko , Wiegand Susanna , van der Ploeg Lex , Fiedorek Fred , Hylan Michelle , Gottesdiener Keith

Background: The hypothalamic leptin–melanocortin signalling pathway is a critical regulator of human appetite and weight regulation. Monogenetic defects in the POMC gene, the MSH ligand generating PC1 gene and the MSH receptor gene MC4R lead to severe early onset and leptin-resistant obesity. In PWS, where the function of genes such as MAGEL2 are impaired, the Magel2-/- mouse model revealed decreased POMC neuronal functioning as one c...

hrp0086fc13.6 | Management of Obesity | ESPE2016

Treatment for Early Onset and Extreme Obesity in Two POMC Deficient Patients: Successful Weight Loss with the Melanocortin-4 Receptor Agonist Setmelanotide

Kuhnen Peter , Clement Karine , Gottesdiener Keith , Fiedorek Fred , van der Ploeg Lex , Wiegand Susanna , Blankenstein Oliver , Gruters Annette , Krude Heiko

Background: POMC deficiency is an extremely rare monogenetic obesity syndrome generally characterized by early onset hyperphagia, red hair and adrenal insufficiency. So far treatment of obesity and hyperphagia with MSH substitution failed, either due to ineffectiveness or side effects of available MC4R agonists.Objective and hypotheses: We hypothesized that the new MC-4R agonist setmelanotide might be a treatment option in POMC deficient patients.<p ...