Unraveling Metabolic Involvement in Facioscapulohumeral Dystrophy Through Metabolomics

Study Overview
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Brief Summary
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The pathogenesis of facioscapulohumeral dystrophy (FSHD), one of the most prevalent types of inherited muscle disease, is unknown. The reasons underlying its significant clinical heterogeneity, incomplete penetrance, and sex specific differences in the age of onset, are not currently understood. While metabolic changes associated with this disease have so far deserved little attention, recent studies have pinpointed significant metabolic dysregulation as an emerging driving mechanism in the pathophysiology of this untreatable disease. To test this hypothesis, we will perform a deep metabolic phenotyping in a large cohort of highly clinically characterized FSHD patients at different stage of disease and age/sex-matched controls by state-of-art plasma metabolomic and mitochondrial biomarker profiling. These data will allow attributing specific metabolomic signatures to different stages of the disease in each sex. Metabolic pathway analysis will allow gaining insights into the type of metabolic dysregulation associated with the disease pathogenesis, leading to the identification of targeted metabolic/nutritional interventions and biomarker discovery.

Official Title
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Unraveling Metabolic Involvement in Facioscapulohumeral Dystrophy Through Metabolomics

Conditions
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Facioscapulohumeral Muscular Dystrophy

Intervention / Treatment
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* Other: metabolomic on plasma sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: participant fasting for at least 8 h at the time of blood sampling patient with a molecular diagnosis of FSHD (know number of D4Z4 contractions) patient with a typical FSHD presentation (at least facial, pelvic ans scapular girdles signs) patient with a preserved ability to ambulate at the time of the selection (use of a cane is allowed) Exclusion Criteria: Severe cardiac and respiratory dysfunction. Presence of severe systemic diseases unrelated to FSHD. Presence of uncontrolled diabetes or hypothyroidism. Alcohol or toxic abuse.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| cases<br>patients with molecular diagnosis of facioscapulohumeral dystrophy | Other: metabolomic on plasma sample<br>* metabolic phenotyping by plasma metabolomic and mitochondrial biomarker profiling<br>|
| controls<br>healthy volunteers | Other: metabolomic on plasma sample<br>* metabolic phenotyping by plasma metabolomic and mitochondrial biomarker profiling<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| metabolic profiling | to perform a detailed metabolic profiling by state-of-art plasma metabolomic coupled to the analysis of GDF15 and FGF21, two recently established biomarkers of mitochondrial dysfunction, in symptomatic FSHD patients of different clinical severity compared to controls | results should be obtained within 3 months following the inclusion of the last participant |