Marvel’s MB204 improves social behaviors in Rett mice in study
Developer cites long-lasting effects, is planning clinical trials in 2025
Marvel Biosciences‘ MB204, an experimental treatment for Rett syndrome, was shown to improve social behaviors — with “durable” effects — in a mouse model of the disease.
Based on these results, Marvel intends to seek orphan and/or rare disease designation from the U.S. Food and Drug Administration (FDA) for MB204 in Rett syndrome, the company said in a press release. Such designations could provide benefits such as tax incentives and market exclusivity should the therapy ultimately be approved.
Full preclinical study results are expected at the beginning of 2025, with Phase 1 clinical trials expected to start later in the year.
“MB204 continues to exceed our expectations in pre-clinical studies,” said Mark Williams, PhD, Marvel’s chief science officer. “MB204’s long-last effects are particularly exciting and encouraging.”
Improvements in social behaviors lasted 3 weeks post-treatment
Rett syndrome is caused primarily by mutations in the MECP2 gene, which provides instructions for producing a protein of the same name. That protein regulates the activity of other genes, by switching them on or off. The MeCP2 protein is particularly important for the brain’s development and function.
Mainly affecting females, Rett leads to cognitive, sensory, emotional, and motor issues, usually starting between 6 and 18 months of age. Normal development starts to slow, then stagnate or regress. Autism-like symptoms in Rett include social withdrawal and reduced eye contact.
MB204 is a derivative of istradefylline, a molecule known to block adenosine A2a receptors. The adenosine system is essential for nerve cell function in the brain and has been suggested as a potential therapeutic target in Rett syndrome.
Marvel noted that the therapy was developed to work faster, more effectively, and at lower doses than existing Rett treatments. It is marketed in the U.S., under the brand name Nourianz, for the treatment of Parkinson’s disease.
In the Rett preclinical study, done in collaboration with the International Institute for the Brain (iBRAIN), MB204 was compared with Daybue (trofinetide). Daybue, marketed by Acadia Pharmaceuticals, last year became the first FDA-approved treatment for Rett syndrome. In clinical trials, Daybue led to improved scores on assessments related to fear, anxiety, body rocking, and blank facial expressions.
In this study, mice were treated for two weeks with either compound. Analyses were made when treatment stopped, and weekly thereafter.
According to the company, MB204’s improvements in social behaviors persisted for 21 days, or three weeks, following the dosing period — which “suggests a durable post-treatment and potential neuromodulation [nervous system modulation] effect,” per Marvel. In contrast, mice treated with Daybue showed minimal effects lasting 14 days.
In previous data reported by the company, treatment with MB204 restored social interactions in a mouse model of autism. Treatment with a higher dose also outperformed results seen in healthy mice when analyzing behaviors such as nose contacts, paw contacts, and time spent self-grooming, Marvel stated.
Rod Matheson, Marvel’s CEO, noted that the company is also investigating MB204 for other conditions — for which, he noted, any FDA designations would also be helpful.
“Alongside this program, we are advancing preclinical studies in fragile X syndrome and recently secured a major grant to support preclinical research in Alzheimer’s disease,” Matheson said. “Achieving orphan or rare disease designation for MB204 could also add significant value to our lead asset.”
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