LAMA2 Genetic Correction

August 30, 2024 updated by: Maastricht University

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
7

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The study will only include patients/controls living in The Netherlands

Description

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:

  • MDC1a 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Compare RNA transcription of corrected and not corrected DNA
Time Frame: 1 day
qPCR
1 day
Assess effect LAMA2 mutations on muscle protein quantity (amount of LAMA2)
Time Frame: 1 day
LAMA2 immunostaining
1 day
Assess effect LAMA2 mutations on muscle protein quality (localization of LAMA2)
Time Frame: 1 day
LAMA2 immunostaining
1 day
Assess effect LAMA2 mutations on muscle protein quantity (LAMA2 overall levels)
Time Frame: 1 day
LAMA2 western blot
1 day
Assess effect LAMA2 mutations on muscle protein quality (fibrosis)
Time Frame: 1 day
LAMA2 HE staining
1 day

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Verification of the LAMA2 mutations or exclusion of LAMA2 mutations in controls
Time Frame: 1 day
DNA analysis
1 day
Blood markers to assess level of muscle inflammation, damage and regeneration in MDC1a patients: CK
Time Frame: 1 day
ELISA assay
1 day
Blood markers to assess level of muscle inflammation, damage and regeneration in MDC1a patients: TNFa
Time Frame: 1 day
ELISA assay
1 day
Blood markers to assess level of muscle inflammation, damage and regeneration in MDC1a patients: IL-6
Time Frame: 1 day
ELISA assay
1 day
Blood markers to assess level of muscle inflammation, damage and regeneration in MDC1a patients: SDF1
Time Frame: 1 day
ELISA assay
1 day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Maastricht University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 18, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 18, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 11, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 30, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 3, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 3, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 30, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2024

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MABS03

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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