Duchenne Muscular Distrophy (DMD)
Conditions
Keywords
Duchenne muscular distrophy, Endomysial Fibrosis, Muscular Inflammatory Response, Calcium Homeostasis Dysfunction, Muscle biopsy
Brief summary
Duchenne muscular dystrophy (DMD) is the most common and devastating form of muscular dystrophy, caused by an X-chromosome gene mutation resulting in the absence of the protein dystrophin. Gene therapy by exon skipping or stop codon read-through and cell therapy are at the stage of clinical assays with very promising results. Nevertheless, they will not allow a complete cure of DMD patients and they will concern only specific types of mutations. It is therefore crucial to develop other therapeutic strategies related to the natural history of the disease and targeted not on the dystrophin itself, but on the consequences of its absence. Another crucial pathophysiological pathway in DMD is muscle cell calcium homeostasis, particularly via the ryanodine recepteur (RyR1). Our study focus on the relationship between endomysial fibrosis, abnormal inflammation response and calcium homeostasis dysfunction which are not entirely established in DMD. The identification of the biological mechanisms that play a role in the severity of the phenotype, particularly endomysial fibrosis, should allow the development of targeted pharmacotherapy as a complementary strategy for the future treatment of DMD.
Interventions
OTHERMuscle biopsy
Muscle biopsy
Sponsors
University Hospital, Montpellier
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 15 Years
Healthy volunteers
Yes
Inclusion criteria
* Boy between 2 to 15 years old. * Lack of any infectious disease in the last week before the study. * Consent form signed by parents. Inclusion Criteria for DMD infant * Clinical suspicion of Duchenne Muscular Dystrophy Inclusion Criteria for Control healthy Infant * Lack of any antecedent of congenital cardiac, pulmonary or muscular disease including DMD.
Exclusion criteria
* Subjects who are unable or unwilling to tolerate study constraints * Parents of the subject unable or unwilling to undergo informed consent * Subject with no rights from the national health insurance programme
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quantification of endomysial fibrosis | 1 day (biopsy day) | — |
| quantification of the muscle inflammation | 1 day (biopsy day) | * Measure of the protein (Immunofluorescence and western blot) and mRNA (qRT-PCR) expression of the following markers of muscular inflammation response * Presence and quantification of cellular partners of inflammation and muscle regeneration (M1 (CD68/KP1) and M2 (CD206) macrophages, quiescent and activated satellite cells (CD56/NCAM) and endothelial cells (CD31/PECAM-1)). |
Countries
France
Contacts
Primary ContactFrançois RIVIER, PU PH
Backup ContactStefan Matecki, PU PH
Outcome results
None listed