What side effects are associated with this type of intervention?

Common side effects of gene therapy for Limb-Girdle Muscular Dystrophy, such as SRP-9003, include immune reactions that can cause inflammation, insertional mutagenesis with potential risks of cancer, and mild to moderate symptoms like fever, headache, and fatigue. These side effects are generally transient but require careful monitoring.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved gene therapies for Limb-Girdle Muscular Dystrophy (LGMD). However, investigational treatments like SRP-9003, which involves the delivery of a functional gene to replace or repair a defective gene, are being studied. This approach is similar to other gene therapies in development for various muscular dystrophies, aiming to address the underlying genetic defects. Broader treatment strategies for LGMD include supportive care and experimental therapies, but gene therapy remains a promising area of research.

What other types of research exist?

Promising alternatives to SRP-9003 for LGMD patients include: 1) Antisense oligonucleotide therapies, which can modify RNA splicing to produce functional proteins. 2) CRISPR/Cas9 gene editing, which can directly correct genetic mutations. 3) Exon skipping therapies, which can bypass defective exons during gene expression. 4) Emerging pharmacological treatments that target muscle regeneration and repair pathways. These alternatives are currently under various stages of research and clinical trials, showing potential for future treatment options.

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Gene Therapy

Gene Therapy for Limb-Girdle Muscular Dystrophy

Q: What is the mechanism of action of this treatment?

Gene therapy for Limb-Girdle Muscular Dystrophy (LGMD) involves delivering a functional gene to replace or repair the defective gene causing the disease. This is typically done using vectors like recombinant adeno-associated viruses (rAAV) to introduce a healthy copy of the gene into muscle cells. The new gene can then produce the necessary protein that the defective gene fails to produce, improving muscle function and slowing disease progression. This approach is significant for LGMD patients as it targets the root cause of the disease, potentially offering more effective and long-lasting treatment compared to traditional symptom management therapies.

Phase 1 & 2

Waitlist Available

Research Sponsored by Sarepta Therapeutics, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

A 100 meter walk/run (MWR) test result of ≥40% of predicted for age-, height-, gender-, and weight-matched healthy controls at the screening visit

Presence of β-SG deoxyribonucleic acid (DNA) gene mutations at both alleles

Must not have

Cardiac magnetic resonance imaging (MRI) determined left ventricular ejection fraction (LVEF) <40%

Diagnosis of (or ongoing treatment for) an autoimmune disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline, day 60

Awards & highlights

No Placebo-Only Group

Summary

This trial tests SRP-9003, a gene therapy, in patients with LGMD2E, a type of muscular dystrophy. The therapy uses a harmless virus to deliver a healthy gene into muscle cells to fix the genetic issue. SRP-9003 is a gene therapy that uses a harmless virus to deliver a healthy gene into muscle cells, a method previously demonstrated to be effective in treating muscular dystrophies.

Who is the study for?

This trial is for males and females with Limb-Girdle Muscular Dystrophy, Type 2E (LGMD2E), who have specific gene mutations and experience difficulty in physical activities like running or climbing stairs. Participants must be able to complete a 100 meter walk/run test at a minimum of 40% efficiency compared to healthy individuals.

What is being tested?

The study tests SRP-9003 (bidridistrogene xeboparvovec), which is a new gene therapy delivered once to patients with LGMD2E. It's an open-label trial, meaning both the researchers and participants know what treatment is being given.

What are the potential side effects?

Potential side effects are not explicitly listed but may include typical risks associated with gene therapies such as immune reactions, mild to severe infusion-related responses, and possible unintended effects on other genes or systems.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can walk or run 100 meters at least 40% as well as others my age and size.

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I have mutations in both copies of my β-SG gene.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My heart's pumping ability is below 40%.

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I have been diagnosed with or am being treated for an autoimmune disease.

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I currently have an active viral infection.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline, day 60

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline, day 60

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline, day 60 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Change From Baseline in Quantity of Beta-Sarcoglycan (β-SG) Protein Expression at Day 60, as Measured by Western Blot

Change From Baseline in Quantity of β-SG Protein Expression at Day 60, as Measured by Immunofluorescence

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Cohort 2: SRP-9003Experimental Treatment1 Intervention

Participants will receive a single IV infusion of SRP-9003. Dose will be determined based on the findings from Cohort 1.

Group II: Cohort 1: SRP-9003Experimental Treatment1 Intervention

Participants will receive a single intravenous (IV) infusion of SRP-9003 at a prespecified dose.

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Gene therapy for Limb-Girdle Muscular Dystrophy (LGMD) involves delivering a functional gene to replace or repair the defective gene causing the disease. This is typically done using vectors like recombinant adeno-associated viruses (rAAV) to introduce a healthy copy of the gene into muscle cells. The new gene can then produce the necessary protein that the defective gene fails to produce, improving muscle function and slowing disease progression. This approach is significant for LGMD patients as it targets the root cause of the disease, potentially offering more effective and long-lasting treatment compared to traditional symptom management therapies.

[Recommendations for gene therapy of spinal muscular atrophy with onasemnogene abeparvovec-AVXS-101 : Consensus paper of the German representatives of the Society for Pediatric Neurology (GNP) and the German treatment centers with collaboration of the medical scientific advisory board of the German Society for Muscular Diseases (DGM)].