This study aims to isolate and culture myogenic stem cells called mesoangioblasts from the muscle biopsies to explore if genetic correction of LAMA2 mutations using CRISPR-Cas9 can be achieved and subsequently assess the effect in vitro, as a first…
ID
Source
Brief title
Condition
- Muscle disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Assessment of the effect of LAMA2 mutations on skeletal muscle LAMA protein
quality and quantity and in vitro analysis of CRISPR-Cas9 genetically corrected
mesoangioblasts of MDC1a/LAMA2-MD patients compared with control
mesoangioblasts.
Secondary outcome
- Blood markers muscle inflammation, damage and regeneration: CK, TNFa, IL-6,
SDF1 (ELISA assay).
- DNA analysis for verification of the LAMA2 mutations or exclusion of LAMA2
mutations in controls.
Background 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.
Study objective
This study aims to isolate and culture myogenic stem cells called
mesoangioblasts from the muscle biopsies 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.
Study design
Mono-center observational study
Study burden and risks
Participation does not result in direct benefit for the participant.
The risk of complications associated with the muscle and skin biopsy (1
procedure). In some cases, the muscle biopsy can be painful. Infections and
bleeding afterwards are possible, but rare. Collection of a skin biopsy during
the muscle biopsy procedure does not increase burden or risk of complications.
Only difference in procedure for combined collection of skin and muscle biopsy
is that instead of a 0.5cm incision in the skin for collecting only a muscle
biopsy, a circular punch of 3mm diameter will be made in the anesthetized skin.
Universiteitssingel 50
Maastricht 6229ER
NL
Universiteitssingel 50
Maastricht 6229ER
NL
Listed location countries
Age
Inclusion criteria
LAMA2 mutation carriers:
- Age >18 years
- Heterozygous or homozygous LAMA2 c.5562+5G>C mutation
- Written informed consent
Controls:
- Written informed consent
- Age >18 years
- No muscular dystrophy or other disease known to affect muscle morphology or
function
Exclusion criteria
MDC1 patients and controls:
- No informed consent
- Use of anti-coagulants, anti-thrombotics and other medication influencing
coagulation
- Have a weekly alcohol intake of >= 35 units (men) or >= 24 units (women)
- Current history of drug abuse
- A history of strokes
- Significant concurrent illness
- Ongoing participation in other clinical trials
- Major surgery within 4 weeks of the visit
- Pregnant or lactating women
- Patients unable and/or unwilling to comply with treatment and study
instructions
- Any other factor that in the opinion of the investigator excludes the patient
from the study
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL70962.068.20 |