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Biomarker Shows Promise for Potential Treatment of Facioscapulohumeral Muscular Dystrophy

A novel study published in the Journal of Neuromuscular Diseases has identified a potential disease severity biomarker that brings hope for developing and testing treatments for facioscapulohumeral muscular dystrophy

Amsterdam, NL – There is currently no effective treatment for facioscapulohumeral muscular dystrophy (FSHD), one of the most common neuromuscular diseases, which is caused by an abnormal expression of the transcription factor DUX4. Investigators have now identified a novel promising biomarker, interleukin-6 (IL-6), that correlates with the severity of FSHD. This has the potential to clinically manage the disease and help to assess the efficacy of potential FSHD treatments. Their study is published in the Journal of Neuromuscular Diseases.

“FSHD has a high degree of clinical variability and a lack of treatment for patients,” explained lead investigator Sabrina Sacconi, MD, PhD, Université Côte d’Azur, Centre Hospitalier Universitaire de Nice, Hôpital Pasteur Centre, and Fédération Hospitalo-Universitaire Oncoage, Nice, France. “There are currently a number of companies in the race to develop such treatments. However, the extreme variability and the unpredictable progression of FSHD complicate the development of sensitive outcome measures and biomarkers, which can impede the development of new therapeutics. The emergence of the unified model for FSHD, i.e., abnormal toxic expression of DUX4 and its target genes, brings hope for the development of therapy to treat this disease, as it provides therapeutic targets.”

Given the central role of inflammation in FSHD pathophysiology, investigators retrospectively measured the levels of 20 pro-inflammatory and regulatory cytokines in serum cytokines in 100 adult patients with FSHD1 (51 males and 49 females) to identify potential severity biomarkers. Among all the cytokines tested, IL-6 was the only one with a concentration correlating with clinical severity: the more severe the disease is, the more elevated the IL-6 level is. FSHD patients displayed overall IL-6 levels more than twice as high as controls, and patients with milder disease exhibited lower IL-6 serum concentration than those with severe muscular weakness. These results were confirmed in vivo in an FSHD-like mouse model, suggesting that IL-6 can be used as a FSHD severity biomarker.

“Altogether, the results show that IL-6 levels can be used as a potential new disease severity serum biomarker for FSHD1 patients,” said Dr. Sacconi. “This is a crucial milestone in the search for an effective FSHD therapy. The identification of serum IL-6 as a potential severity biomarker will help us assess the efficacy of newly developed compounds and stratify patients in natural history and clinical trials. It brings hope for the development of therapies to treat this disease.” 

FSHD is one of the most common muscular diseases in adults. The disorder gets its name from muscles that are affected in the face (facio), around the shoulder blades (scapulo), and in the upper arms (humeral). Other arm and leg muscles may be affected in the course of the disease. The degree of muscle weakness may be asymmetrical, differing from one side of the body to the other. The most common form, called FSHD1, is usually inherited as an autosomal dominant genetic condition that results in DUX4 retrogene toxic expression in skeletal muscles.

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Full open access study
: “Identification of Serum Interleukin 6 Levels as a Disease Severity Biomarker in Facioscapulohumeral Muscular Dystrophy” by Marilyn Gros, Andreia M. Nunes, Douglas Daoudlarian, Jonathan Pini, Emanuela Martinuzzi, Susana Barbosa, Monique Ramirez, Angela Puma, Luisa Villa, Michele Cavalli, Nicolae Grecu, Jérémy Garcia, Gabriele Siciliano, Guilhem Solé, Raul Juntas-Morales, Peter L. Jones, Takako Jones, Nicolas Glaichenhaus, and Sabrina Sacconi (DOI: 10.3233/JND-210711), Journal of Neuromuscular Diseases, Volume 9, issue 1 (2022). The open access article is available online at: /content.iospress.com/articles/journal-of-neuromuscular-diseases/jnd210711.   

This work was funded by the Centre Hospitalier Universitaire de Nice, the National Research Agency through the “Investments for the Future” (LABEX SIGNALIFE), the University Hospital Federation (FHU) “OncoAge,” and the National Institute of Arthritis, Musculoskeletal, and Skin Diseases, NIH.

Contact Diana Murray, IOS Press (+1 718-640-5678 or d.murray@iospress.com) for additional information. Journalists who wish to interview the authors should contact Sabrina Sacconi (+33 4 92 03 90 02 or sacconi.s@chu-nice.fr). 

About the Journal of Neuromuscular Diseases
The Journal of Neuromuscular Diseases (JND) facilitates progress in understanding the molecular genetics/correlates, pathogenesis, pharmacology, diagnosis, and treatment of acquired and genetic neuromuscular diseases (including muscular dystrophy, myasthenia gravis, spinal muscular atrophy, neuropathies, myopathies, myotonias, and myositis). The journal publishes research reports, reviews, and short communications. Guided by Editors-in-Chief Carsten G. Bönnemann (National Institute of Neurological Disorders and Stroke, NIH) and Hanns Lochmüller (Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Canada), JND is dedicated to providing an open forum for original research in basic science, translational, and clinical research that will improve our fundamental understanding and lead to effective treatments of neuromuscular diseases. iospress.com/journal-of-neuromuscular-diseases 

About IOS Press
IOS Press is an independent international scientific, technical, medical (STM) publishing house established in 1987 in Amsterdam. We produce around 90 journals and 70 books annually in a broad range of subject categories, primarily specializing in biomedical and life sciences (including neurosciences, medical informatics, cancer research, rehabilitation) and physical sciences (including computer sciences, artificial intelligence, engineering). In addition, we offer specialized services that support scientific advancement. iospress.com