/ News, Research

Groundbreaking Research Initiative awarded to tackle RYR1-Related Myopathies: New Hope for Patients (Treves Lab)

Susan Treves - quote

ZNM – Together Strong! e. V. has granted a pivotal research project led by Susan Treves’ lab at the Department of Biomedicine with the long-term goal of developing a targeted treatment for patients with RYR1-Congenital Myopathy (RYR1-CNM). Epigenetic enzyme inhibitors will be investigated as therapeutic agents for this genetically defined centronuclear myopathy through the development of an in vitro-based cell assay using immortalized human muscle cell lines.

Centronuclear myopathies (CNM) are exceedingly rare muscle disorders associated with mutations in several genes, including RYR1, which encodes a principal sarcoplasmic reticulum calcium release channel. While the precise mechanisms triggered by recessive RYR1 mutations remain elusive, a common observation in most patients is the diminished content of RyR1 protein. This deficiency is accompanied by an up-regulation of epigenetic enzymes, specifically class II histone de-acetylases (HDACs) and DNA methyltransferases (DNMT), in the muscles of patients. Thedysregulation leads to a domino like effect which leads to changes in the expression of many proteins including a reduction in RyR1 Ca2+ channels, resulting in weaker muscles, mis-regulation of various transcripts, and abnormal gene expression.

The primary objective of this study, awarded funding of €45,000 by ZNM – Together Strong! e. V. , is to define, in a pre-clinical setting, the potential therapeutic applications of HDAC and DNMT inhibitors. This involves determining optimal drug doses, exploring effective drug combinations, and identifying biomarkers crucial for monitoring treatment response. The ultimate goal is to pave the way for a phase 1/2 clinical trial involving patients affected by RYR1-CNM.

We congratulate the Treves Lab for this great achievement.

About Centronuclear Myopathies 

Centronuclear myopathies (CNM) are a group of exceptionally rare muscle disorders linked to mutations in various genes, including RYR1. Individuals with this genetic mutation typically exhibit symptoms such as muscle weakness, challenges in walking and climbing stairs. Importantly, the lifespan of those affected is generally within the normal range, and their cognitive development remains unaffected.

About ZNM – Zusammen Stark! e.V. 

ZNM – Zusammen Stark! e. V. (CNM – Together Strong!) is a self-help association for myotubular myopathy and other centronuclear myopathies (CNM). We represent 258 individuals from 92 families with a CNM in Germany, the Netherlands, Austria, Switzerland, and Belgium. As a self-help organization, our main goal is to connect those affected and their families and to support each other in our daily lives. This is mainly done through our yearly family conference, webinars, and our closed Facebook support group. We also actively invest in research to find a treatment for these conditions. For more information, please visit https://znm-zusammenstark.org

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