The Potential of MCHR1 Antagonists in Narcolepsy: Thomas Scammell, MD

WATCH TIME: 3 minutes

“This is actually a new mechanism for clinicians to learn about—I think many doctors who are familiar with the treatment of narcolepsy know about the conventional medications, but this is a novel signaling molecule, and there may be many novel benefits, but there could also be some novel concerns. So, we really need to work towards thoroughly studying the safety and efficacy of this medication as it comes through the pipeline.”

Harmony Biosciences recently acquired HBS-102 (formerly CSTI-100; ConSynance Therapeutics), a melanin concentrating hormone receptor 1 (MCHR1) antagonist with the potential for a novel approach to the treatment of narcolepsy, particularly symptoms of rapid eye movement (REM) sleep dysregulation—cataplexy, hallucinations, and sleep paralysis.¹ Following the acquisition, Thomas Scammell, MD, professor of neurology, Beth Israel Deaconess Medical Center, spoke with NeurologyLive on the potential of MCHR1 antagonists. 

Scammell noted that the mechanism has yet to be tested in humans, with he and his team investigating a separate compound, SNAP 94847, in an orexin knockout mouse model of narcolepsy, seeing significant reduction in cataplexy events.² Harmony is currently putting forth efforts to initiate a phase 2 clinical trial of HBS-102 once an investigational new drug application is open. 

Benefits for patients with narcolepsy included the fact that the MCHR1 antagonists work differently than existing treatment options, which may lead to reduction in cataplexy for patients who have not had results with other medications. Scammell noted some patients with narcolepsy do have reductions in cataplexy when treated with antidepressants or oxybate, while others do not show these full improvements. In introducing MCHR1 antagonist, experts hope to elicit better overall efficacy for this patient population and/or better efficacy for patients that have been hard to treat. 

REFERENCES

1. Harmony Biosciences acquires asset with novel mechanism of action for the potential treatment of narcolepsy and other are neurological diseases. News release. Harmony Biosciences. August 9, 2021. Accessed November 1, 2021. https://www.prnewswire.com/news-releases/harmony-biosciences-acquires-asset-with-novel-mechanism-of-action-for-the-potential-treatment-of-narcolepsy-and-other-rare-neurological-diseases-301350524.html
2. Naganuma F, Bandaru SS, Absi G, Mahoney CE, Scammell TE, Vetrivelan R. Melanin-concentrating hormone neurons contribute to dysregulation of rapid eye movement sleep in narcolepsy. Neurobiol Dis. 2018;120:11-24. doi:10.1016/j.nbd.2018.08.012