NCT06582537

LAMA2 Genetic Correction

Ex Vivo Genetic Correction of LAMA2 Mutation(s) in Myogenic Stem Cells of Patients with Merosin-deficient Congenital Muscle Dystrophy Type 1a (MDC1a)

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 7 (actual)
• Sponsor: Maastricht University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

Merosin-deficient congenital muscle dystrophy type 1a (MDC1a), or LAMA2 muscular dystrophy (LAMA2-MD) is a severe autosomal recessive form of muscular dystrophy that is caused by homozygous or compound heterozygous mutations in the laminin alpha 2 (LAMA-2) gene. Many different LAMA-2 mutations have been reported. In most cases, MDC1a is diagnosed within the first year of life, and is characterized by hypotonia, delayed motor development and white matter abnormalities. Currently, no efficient treatment is available for this patient group. Generally, MDC1a patients with mutations causing a premature stop codon are most severely affected (early onset LAMA2-MD) and patients with missense mutations are generally affected more mild affected and more late-onset (late onset LAMA2-MD). However, large variation in disease severity and clinical course is observed, even between individuals with the same mutation, e.g. the LAMA2 c.5562+5G\>C mutation, which is frequently observed in Dutch MDC1a patients. This study aims to isolate and culture fibroblasts and myogenic stem cells called mesoangioblasts from the skin and muscle biopsies of adult LAMA2 mutation carriers to explore if genetic correction of LAMA2 mutations using CRISPR-Cas9 can be achieved and subsequently assess the effect in vitro, as a first step towards therapy development.

Conditions

• MDC1A

Interventions

Type	Name	Description
PROCEDURE	Participants sample collection	A skeletal muscle biopsy and a venous blood sample will be collected. The skin biopsy will be obtained during the incision needed for the muscle biopsy.

Timeline

• Start date: 2020-07-01
• Primary completion: 2024-07-18
• Completion: 2024-07-18
• First posted: 2024-09-03
• Last updated: 2024-09-03

Locations

1 site across 1 country: Netherlands