The MC4R pathway in the hypothalamus is a key neuronal pathway in regulating hunger, caloric intake, and energy expenditure1
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.
![Impaired MC4R pathway activity](/static/hcp-bbs-mod-impaired-4c7555de4444a803b271b85af1f9b341.png)
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
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- Activation of the MC4R pathway can help to increase satiety signals and energy expenditure, therefore reducing hunger, and consequently, food intake and weight.6
![IMCIVREE activates the MC4 receptor in the MC4R pathway](/static/hcp-ppl-moa-neuron-bc58d9d07fe3262491dfcbea9551cbb9.png)
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.