Facioscapulohumeral Muscular Dystrophy
Conditions
Brief summary
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.
Interventions
OTHERmetabolomic on plasma sample
metabolic phenotyping by plasma metabolomic and mitochondrial biomarker profiling
Sponsors
University of Modena and Reggio Emilia
Federico II University
University Hospital, Angers
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| metabolic profiling | results should be obtained within 3 months following the inclusion of the last participant | 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 |
Contacts
Primary ContactMarco Spinazzi, MD, PhD
Outcome results
None listed