ESPE Abstracts

Background: Alström syndrome (AS) is a rare genetic ciliopathy characterized by severe early-onset obesity, hyperphagia, retinal dystrophy, hearing loss, and cardiomyopathy. Rodent studies suggest that cilia play an important role in the leptin-MC4R pathway, which regulates energy balance and body weight. Setmelanotide, a peptide agonist of the MC4R, has led to weight loss in individuals affected by other rare genetic obesity disorders resulting from dysfunction in this p...

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...

Introduction: The hypothalamic melanocortin-4 receptor (MC4R) pathway plays a vital role in energy balance. Genetic defects in the MC4R pathway may result in severe early onset obesity.Objective: The TEMPO registry (NCT03479437) aims to identify and enroll approximately 1000 participants with rare genetic forms of obesity that are potentially related to key genes, upstream or downstream, of the MC4R. In addition, the TEMPO registry will evaluate the burd...

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 ...

Background: Bardet-Biedl syndrome (BBS) causes early-onset extreme obesity and hyperphagia that is hypothesized to arise from leptin receptor dysfunction. Setmelanotide, a melanocortin-4 receptor (MC4R) peptide agonist, has been shown to induce weight loss in individuals affected by other rare genetic obesity disorders resulting from leptin-melanocortin pathway dysfunction upstream of MC4R.Objective: Report preliminary data on body weight, hunger scores,...