Professor Yorgo Modis leads collaborative project on MORC2-related disorder

Professor Yorgo Modis (Department of Medicine, University of Cambridge) is leading a research project with MORCure, a patient-led global charity that leads research, innovation and best practice for individuals with MORC2-related disorder (M2RD), to generate new insights into how genetically inherited variants of the MORC2 gene cause disease, including severe neuropathies in young children.

M2RD is a rare and often devastating genetic condition that primarily affects young children, disrupting nerve function and development. As genetic testing becomes more widespread, the number of identified cases is rising — yet scientific understanding of how mutations in the MORC2 gene cause disease remains limited. This gap in knowledge has slowed diagnosis, care pathways and the development of treatments.

Previous peer-reviewed studies published by Modis and colleagues have shown that MORC2 plays a vital role in regulating gene expression from the earliest stages of human embryonic development. In this new project, the Modis group will apply a combination of state-of-the-art computational approaches, including AI-driven molecular modeling tools and molecular dynamics simulations, to obtain a detailed understanding of how specific genetically inherited mutations affect the function and regulation of the MORC2 protein.

“With an increasing number of families affected by M2RD, MORCure addresses an important need for a better understanding of the disorder, how to diagnose it and ultimately how to treat it”, said Prof. Modis. “We will draw on our deep expertise on MORC2 molecular structure and function to determine the effects of mutations associated with M2RD on the ability of MORC2 to perform its essential gene-regulatory functions. Integrating insights from powerful neural network-based computational models and molecular dynamics simulations on some of the fastest available processors will allow us to make accurate predictions of the individual effects of each known M2RD-associated mutation”.

This project paves the way for experimental validation of our understanding of the molecular mechanism of transcriptional regulation by MORC2. MORCure and Prof. Modis plan to leverage these advances to enable the development of new diagnostics and medicines for M2RD patients.

MORCure co-founder and CEO, Anna-mai Andrews, notes “We are thrilled to have recruited Prof. Modis to apply his expertise and cutting-edge approaches to help us understand MORC2-related disorder. We firmly believe the work of Prof. Modis and his team will lead the way to identifying new ways to diagnose and treat this disorder.”

MORCure currently works with a distinguished Medical Advisory Board and Board of Trustees to raise awareness of M2RD around the world, connect patients and clinicians, and promote research on a disorder that remains significantly underdiagnosed and misdiagnosed.