Flagship projects

An as yet unexplored pathway in Steinert disease

EpiDM: chemical modifications of RNA in myotonic dystrophy 

The EpiDM project explores a still little-studied dimension of myotonic dystrophy type 1: the role of a chemical modification of RNA, known as m6A, in the mechanisms that progressively disrupt muscle and other organs. 

Scientific challenge

Myotonic dystrophy type 1 (DM1), also known as Steinert disease, is caused by a toxic RNA that disrupts how cells work. Yet RNA can itself carry chemical modifications capable of influencing its stability, its use and its impact on cells. These mechanisms, brought to light by messenger RNA vaccines, are being studied in cancer and in neurological diseases, but remain largely unknown in muscle diseases. Exploring this avenue could reveal mechanisms of DM1 that are still invisible.

Key questions to unravel

Early results suggest that m6A is altered in patients. The team wants to establish whether this modification contributes directly to the disease, which RNAs are involved and which cellular processes are disrupted. The aim is to identify a new layer of regulation involved in the muscle and multisystem manifestations of DM1.

Scientific and methodological approach

The researchers will analyse RNA from the muscle cells of patients and from experimental models in order to measure m6A levels precisely. Using next-generation sequencing, they will map where these modifications sit along the RNAs and study their biological consequences. This approach will make it possible to identify the RNAs affected and the cellular mechanisms that are deregulated.

This project will deliver the first study of m6A in Steinert disease. It will provide a better understanding of the mechanisms behind the disease and explore an area that is still largely unexplored in muscle diseases. In the longer term, the knowledge generated could contribute to the identification of new biomarkers, open up new therapeutic avenues and benefit other muscle diseases, muscle regeneration and the study of muscle ageing.

Frédérique Rau, researcher at the Institute’s Center of Research in Myology

Expected impact on research and clinical practice

EpiDM could provide the first maps of m6A in DM1-affected muscle, reveal new biomarkers and open up a therapeutic avenue that is still unexplored. The knowledge generated could also benefit other neuromuscular diseases, muscle regeneration or muscle ageing.