Endomysial Fibrosis, Muscular Inflammatory Response and Calcium Homeostasis Dysfunction in Duchenne Muscular Dystrophy | DuchenneXchange

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Endomysial Fibrosis, Muscular Inflammatory Response and Calcium Homeostasis Dysfunction in Duchenne Muscular Dystrophy

key information

study id #: NCT01823783

condition: Duchenne Muscular Distrophy (DMD)

status: recruiting

purpose:

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.

intervention: Muscle biopsy

mechanism of action: No pharmaceutical intervention

results: https://clinicaltrials.gov/ct2/show/results/NCT01823783

last updated: November 22, 2018

study details

start date: November 7, 2012

estimated completion: June 2018

phase of development: N/A

size / enrollment: 50

primary outcomes:

  • Quantification of endomysial fibrosis [Time Frame: 1 day (biopsy day)]
  • quantification of the muscle inflammation [Time Frame: 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)).

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

study contacts

sponsor: University Hospital, Montpellier

contacts:
François RIVIER (PU, PH), f-rivier@chu-montpellier.fr;
Stefan Matecki (PU, PH), s-matecki@chu-montpellier.fr

investigators: François RIVIER, PU PH

locations: France