COMBINEDBrain-Led Initiative to Evaluate RNA-Based Therapeutic Platform for Neurodevelopmental Conditions

Rare Daily Staff

A coalition of rare disease organizations is backing a new research effort at Johns Hopkins University to evaluate an RNA-based therapeutic platform that could address a shared genetic mechanism across multiple neurodevelopmental disorders.

The initiative is being led by COMBINEDBrain in collaboration with researchers at Johns Hopkins. The project will focus on disorders caused by haploinsufficiency, a condition in which a single functional copy of a gene fails to produce sufficient protein for normal biological function.

The collaboration includes IDefine – The Kleefstra Syndrome Foundation; the Koolen-de Vries Syndrome Foundation; MED13L Foundation; DLG4 SHINE Foundation; and DYRK1A Syndrome International. By pooling funding, patient data, and scientific expertise, the groups aim to accelerate evaluation of a shared therapeutic strategy that could have implications across multiple rare disease populations.

Jeff Coller, professor of RNA biology and therapeutics at Johns Hopkins University and professor of molecular biology and genetics at the Johns Hopkins University School of Medicine, is leading the research. His lab has developed a poly(A)-mimetic platform—referred to as “mRNA boosters”—designed to increase protein production from a patient’s existing functional gene copy.

Preclinical work has shown that the platform can enhance gene expression across several targets associated with neurodevelopmental disorders in both cellular and animal models. The current study will extend that work into patient-derived cellular models representing each of the participating conditions, with the goal of assessing whether the approach can restore gene expression in a disease-relevant context.

“This collaboration reflects our commitment to pursuing innovative research opportunities for individuals and families affected by Kleefstra syndrome,” said Geoff Rhyne, co-founder and CEO of IDefine. “By working alongside other rare disease organizations that share a common biological mechanism, we can support research that would be difficult to pursue independently while helping advance knowledge that may benefit multiple patient communities.”

The initiative is being coordinated through COMBINEDBrain, a consortium that brings together rare disease foundations to advance therapeutic development through shared resources, data, and research infrastructure. The model has gained traction in recent years as patient-led organizations increasingly seek to de-risk early-stage research by aligning around common biological pathways rather than single-gene indications.