Our group has been dedicated to exploring new therapeutic avenues for managing Duchenne Muscular Dystrophy (DMD) for over a decade. Currently, glucocorticoids are the only routinely available treatment for DMD patients, highlighting the urgent need for alternative therapies. Consequently, our research has focused on two promising approaches over the past few years.
The first approach involves studying adiponectin, a hormone with numerous beneficial effects, including muscle tissue targeting. Adiponectin mimics have then been developed to replicate its effects and facilitate their production and development as medical drugs. Among these mimics, AdipoRon and ALY688 have shown significant beneficial effects on the skeletal muscle of mdx mice, the most widely used animal model of DMD. Moreover, their positive effects have been replicated in human myotubes derived from DMD patients.
The second approach is testing inflammasome inhibitors, such as MCC950. These inhibitors have demonstrated a positive impact on the inherent inflammation associated with DMD, both in the skeletal muscle of mdx mice and in human myotubes.
Through these innovative strategies, we aim to improve the management and treatment outcomes for DMD patients.
Team members
- Sonia Brichard, MD, PhD
- Dr Peter Van den Bergh, MD, PhD
- Dr Nicolas Dubuisson, MD, PhD
- Michel Abou-Samra, PhD
Ongoing Projects
Our current aim is to test ALY688 on the cardiac muscle, as cardiomyopathy is now the leading cause of death in DMD patients. In addition, their effect will also be evaluated in combination with gene therapy to improve their potency. Our compounds will also be tested in other muscle disease such as myositis and limb girdle muscle dystrophies (LGMD).
Key publications
- Abou-Samra M, Lecompte S, Schakman O, Noel L, Many MC, Gailly P, Brichard SM. Involvement of adiponectin in the pathogenesis of dystrophinopathy. Skelet Muscle. 2015 Aug 7;5:25. doi: 10.1186/s13395-015-0051-9.
- Abou-Samra M, Boursereau R, Lecompte S, Noel L, Brichard SM. Potential Therapeutic Action of Adiponectin in Duchenne Muscular Dystrophy. Am J Pathol. 2017 Jul;187(7):1577-1585. doi: 10.1016/j.ajpath.2017.02.018. Epub 2017 Apr 29. PMID: 28463682.
- Abou-Samra, M., Selvais, C. M., Dubuisson, N., & Brichard, S. M. (2020). Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together?. International journal of molecular sciences, 21(7), 2620. doi: 10.3390/ijms21072620
- Dubuisson N, Versele R, Davis-López de Carrizosa MA, Selvais CM, Abou-Samra M and Brichard SM,. Inflammasome inhibitors for the treatment of muscular dystrophies. Front. Immunol., 07 December 2022. Sec. Inflammation. doi: 10.3389/fimmu.2022.1049076
- Dubuisson N, Versele R, Davis-López de Carrizosa MA, Selvais CM, Noel L, Planchon C, Van den Bergh PYK, Brichard SM, Abou-Samra M. The Adiponectin Receptor Agonist, ALY688: A Promising Therapeutic for Fibrosis in the Dystrophic Muscle. Cells. 2023 Aug 19;12(16):2101. doi: 10.3390/cells12162101.
- Dubuisson N, Versele R, Nel L, Selvais CM, Abou-Samra M and Davis-López de Carrizosa MA; Histological Methods to Assess Skeletal Muscle Degeneration and Regeneration in Duchenne Muscular Dystrophy. Int. J. Mol. Sci. 2022, 23(24), 16080; https://doi.org/10.3390/ijms232416080