Publications by authors named "Philipp M Krabusch"
Article Synopsis
- Increasing evidence suggests that epigenetic changes, particularly DNA methylation of the POMC gene, can increase the risk of obesity, with a notable 1.4-fold risk linked to specific hypermethylation patterns.
- A human embryonic stem cell model was used to study how these methylation states are established early in development, showing that reduced DNA methylation is associated with the formation of hypothalamic neurons that express the POMC gene.
- Treatment with an MC4R agonist in individuals with hypermethylation resulted in an average body weight reduction of about 4.66% over several months, highlighting a potential therapeutic approach for addressing this epigenetic obesity risk variant.
Introduction: Individuals with proopiomelanocortin (POMC) or leptin receptor (LEPR) deficiency are young and experience severe obesity, hyperphagia, and comorbidities, which can impair quality of life (QOL).
Methods: Two pivotal Phase 3 trials explored the effect of setmelanotide on body weight and hunger in individuals with obesity due to POMC (NCT02896192) or LEPR (NCT03287960) deficiency. QOL and depression were investigated in parallel using the disease-specific, age-appropriate Impact of Weight on Quality of Life-Lite (IWQOL-Lite), Pediatric Quality of Life Inventory (PedsQL), and Patient Health Questionnaire-9 (PHQ-9).
Background And Objectives: Gene mutations within the leptin-melanocortin signaling pathway lead to severe early-onset obesity. Recently, a phase 2 trial evaluated new pharmacological treatment options with the MC4R agonist setmelanotide in patients with mutations in the genes encoding proopiomelanocortin (POMC) and leptin receptor (LEPR). During treatment with setmelanotide, changes in skin pigmentation were observed, probably due to off-target effects on the closely related melanocortin 1 receptor (MC1R).
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