Impact of the Melanocortin-4 Receptor Agonist Setmelanotide on MASLD and Kidney Function in Bardet-Biedl Syndrome.

This study looked at a medication called setmelanotide in 26 people with Bardet-Biedl Syndrome (BBS) to see if it could help with some of the serious health problems that come with this condition. All patients in the study had fatty liver disease (a condition where fat builds up in the liver), and many also had kidney problems and struggled with constant hunger and obesity. After 6 months of treatment with setmelanotide, the researchers found encouraging results. Most importantly, 85% of patients saw their fatty liver disease either completely resolve or significantly improve. The medication also helped improve kidney function, reduced excessive hunger, lowered body fat, and helped with weight management. Interestingly, the liver improvements happened even in patients who didn't lose much weight, suggesting the medication directly helps the liver beyond just weight loss. This is promising news because setmelanotide is already an approved medication (not experimental), and this real-world study shows it may help with multiple aspects of BBS beyond just hunger and weight - including serious complications like liver and kidney problems. However, this was a relatively small study over just 6 months, so longer-term studies with more patients would help confirm these benefits and safety over time.

The melanocortin-4 receptor agonist setmelanotide compensates for upstream gene defects in the brain leptin-melanocortin pathway and reduces hyperphagia and obesity in selected monogenic obesity forms and Bardet-Biedl syndrome (BBS). We aimed to evaluate the short-term impact of setmelanotide treatment in BBS presenting original real-world data focusing on metabolic dysfunction-associated steatotic liver disease (MASLD) and kidney function. This monocentric, prospective observational cohort study was performed between June and December 2023 and included patients above the age of 6 years with genetically confirmed BBS, obesity, and/or hyperphagia and planned setmelanotide therapy. Ultrasound examination of the liver including shear wave elastography, dispersion and attenuation imaging (ATI), a bioimpedance analysis, and a hyperphagia questionnaire survey were applied in addition to clinical data collection. Twenty-six patients with BBS (mean age 19.2 years, range [6.2; 51.8]; mean body mass index (BMI) z-score 2.95, range [1.32; 4.84]) were included. All were classified with MASLD (54% S3, 23% each S1 and S2). After 6 months of setmelanotide treatment, estimated glomerular filtration rate increased up to 10.1 mL/min/1.73 m² (95% confidence interval (CI) [4.3; 15.9]). The following parameters also improved: BMI z-score -0.5 (95% CI [-0.6; -0.3]); hyperphagia score -12.3 (95% CI [-15.5; -9.0]); total body fat -3.1% (95% CI [-5.7; -0.5]); ATI -0.14 dB/cm/MHZ (95% CI [-0.17; -0.11]). A total of 85% of patients exhibited either resolution of MASLD or stabilization at grade S1. MASLD improvement correlated only with liver size, not BMI reduction. Setmelanotide treatment is associated with improvement of MASLD independent of BMI reduction as well as increased glomerular filtration rate in BBS.