The MC4R pathway in the hypothalamus is a key neuronal pathway in regulating hunger, caloric intake, and energy expenditure1
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- The BBSome
- Leptin binding to LEPR triggers a signaling cascade, including secretion of alpha-melanocyte-stimulating hormone (α-MSH) from the POMC neuron, which binds to the MC4 receptor to regulate energy expenditure and satiety.
Ciliary dysfunction in the hypothalamus leads to MC4R pathway impairment, which is a root cause of hyperphagia and obesity in BBS
- In people with BBS, a variant in one or more BBS genes can disrupt the BBSome, leading to ciliary dysfunction and disruption of LEPR signaling.
- Alpha-melanocyte-stimulating hormone (α-MSH) production is impaired or deficient, preventing activation of the MC4 receptor, therefore impairing regulation of energy expenditure and satiety signaling.
IMCIVREE is the first and only precision medicine to target impairment in the hypothalamic MC4R pathway, a root cause of hyperphagia and obesity in BBS1,6
- IMCIVREE, an MC4R agonist, acts in place of alpha-melanocyte-stimulating hormone (α-MSH) to activate the MC4 receptor, to reestablish MC4R pathway activity.6-8
- Activation of the MC4R pathway can help to increase satiety signals and energy expenditure, therefore reducing hunger, and consequently, food intake and weight.6
MC4R=melanocortin-4 receptor; POMC=proopiomelanocortin.
References: 1. Eneli I et al. Appl Clin Genet. 2019;12:87-93. 2. Seo S et al. Hum Mol Genet. 2009;18(7):1323-1331. 3. Blaess S et al. J Clin Invest. 2021;131(8):e148903. doi:10.1172/JCI148903. 4. Huvenne H et al. Obes Facts. 2016;9(3):158-173. 5. Focșa IO et al. Biomed Rep. 2021;15(6):103. doi:10.3892/br.2021.1479. 6. IMCIVREE [prescribing information]. Boston, MA. Rhythm Pharmaceuticals, Inc. 7. Trapp CM et al. Curr Opin Endocrinol Diabetes Obes. 2023;30(2):136-140. 8. Haws R et al. Diabetes Obes Metab. 2020;22(11):2133-2140. doi:10.1111/dom.14133.