The leptin melanocortin signaling pathway plays a pivotal role in body weight regulation within the hypothalamus. Gene mutations within this cascade are leading to early onset obesity and severe hyperphagia in rodents and humans. For the affected patients it is extremely difficult to stabilize body weight based on the persisting hunger feeling. Traditional treatment options (increased exercise, reduced caloric intake) are not effective in most cases. Therefore, there is a need to identify new treatment options because otherwise the long-term prognosis regarding health and life expectancy is serious for these patients. Until recently only leptin deficient patients could be treated successfully with metreleptin. This replacement therapy is leading to a normalization of hunger scores and body weight. However, leptin treatment is not successful in patients with LEPRor POMCmutations. In an investigator-initiated proof-of-concept trial, we have treated POMC and LEPR deficient patients with a MC4R agonist. This led to a significant reduction of hunger feeling and body weight. However, further studies are needed to gain insights into the impact of this pharmacological treatment option on body weight and to examine, whether further groups of patients might benefit from this pharmacological treatment option.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology