FSHD: Hypermorphic SMCHD1 variants

Background
Facioscapulohumeral muscular dystrophy (FSHD) is a progressive muscle disease for which no cure is available. FSHD is caused by the misexpression of the transcription factor DUX4 in skeletal muscle. DUX4 expression in skeletal muscle is regulated by several factors, and one of the key factors in preventing DUX4 expression in skeletal muscle is SMCHD1. In patients with FSHD type 2, SMCHD1 variants are found that decrease SMCHD1 function. We have now identified several SMCHD1 variants that potentially increase SMCHD1 function in healthy individuals. In this project, we aim to understand the mechanisms by which these SMCHD1 variants increase SMCHD1 function with the ultimate goal to develop an SMCHD1-centered therapy for FSHD.

Methods
We use animal models and patient-derived (muscle) cell lines and state-of-the-art molecular and cell biology techniques to understand the mechanisms underlying increased SMCHD1 function in healthy individuals carrying a hypermorphic SMCHD1 variant.

Relevance
There is currently no therapy available for FSHD. This project explores the potential of SMCHD1-based therapy in FSHD.

Financiering: FSHD Society; Spieren voor Spieren