Facioscapulohumeral Muscular Dystrophy (FSHD) is a rare, progressive neuromuscular disorder affecting over 52,000 people in Europe, including around 5,000 in France. It leads to muscle weakness, fatigue, loss of mobility, and — in severe cases — permanent disability. To date, no curative treatment exists. While gene therapy and pharmacogenetics are being explored, the underlying mechanisms of FSHD remain insufficiently understood. Despite growing research interest, recent clinical trials have not met expectations, and most therapeutic approaches remain in early development.

Since the early 2000s, researchers from the PHYMEDEXP laboratory (INSERM, CNRS, University of Montpellier) led by Prof. Dalila Laoudj-Chenivesse, in collaboration with the department of Physiology, CHU de Montpellier, have identified a significant link between facioscapulohumeral muscular dystrophy (FSHD) and oxidative stress. Their studies revealed increased levels of oxidative damage in both muscle and blood samples from patients with FSHD, as well as deficiencies in essential antioxidants such as vitamins C and E, zinc and selenium (Turki et al, 2012). They also observed a correlation between this oxidative imbalance and reduced muscle strength and endurance, suggesting that oxidative stress plays a crucial role in the pathogenesis of FSHD. These findings were consistent with broader scientific research, further supporting the hypothesis that oxidative stress plays a crucial role in FSHD pathogenesis. Other studies from Prof. Laoudj-Chenivesse’s team and others have also demonstrated the FSHD specificity of this defect is also underscored by the susceptibility of primary muscle cells to oxidative agents and alteration in gene expression and protein synthesis involved in oxidative stress response [Barro et al., J Cell Mol Med. 2010; …].

In 2010, the FSHD group led by Prof. Dalila Laoudj-Chenivesse (PHYMEDEX unit) in collaboration with the Department of Physiology at CHU de Montpellier, established that oxidative stress significantly contributes to the development of Facioscapulohumeral Muscular Dystrophy (FSHD) through various analyses (Laoudj et al., 2005; Barro et al., 2010; Turki et al., 2012; Wilson et al., 2018). This indicates that antioxidants may improve patient outcomes. A randomized placebo-controlled trial with 54 FSHD patients (NCT01596803) found that four months of antioxidant supplementation—vitamins C and E, L-selenomethionine, and zinc—was safe and significantly improved muscle function (Passerieux et al., 2015; Wilson et al., 2024), resulting in Orphan Drug Designation from the EMA in 2016. Individualized dosing was necessary due to antioxidant imbalances and patients' nutritional deficiencies (Amzali et al. 2023), highlighting risks associated with unsupervised antioxidant use. To address these issues, a comprehensive five-year personalized care program was launched in 2015 with the FSHD group at CHU Montpellier (NCT02622438). This program, enrolling 152 patients, included tailored supplementation and produced long-term benefits in muscle function, daily performance, and quality of life, demonstrating the approach's relevance. Further research continues to underscore the importance of oxidative stress and antioxidant therapy in FSHD muscle disease management (Denny and Heather, 2017).

CPP obtained from ANSM - promotor CHU NANTES