Gene Therapy (AT132) for Myotubular Myopathy
(ASPIRO Trial)
What You Need to Know Before You Apply
What is the purpose of this trial?
The trial aimed to explore the use of a gene therapy called AT132 for a rare muscle condition known as X-linked myotubular myopathy (XLMTM). XLMTM is a genetic disorder that impairs muscle function due to a mutation in the MTM1 gene, primarily affecting young children. The trial tested whether AT132 could improve muscle function by introducing a healthy version of the gene into the body. However, severe complications and fatalities led to the trial's suspension, and no new participants are being enrolled. Originally, the trial targeted boys under 5 years old with XLMTM who required mechanical breathing support. As a combined Phase 2 and Phase 3 trial, it focused on assessing the treatment's effectiveness in an initial, smaller group and was in the final step before seeking FDA approval.
Will I have to stop taking my current medications?
The trial protocol does not specify if participants must stop taking their current medications. However, participants must not have taken pyridostigmine or any medication to treat XLMTM within 3 months before the trial starts, and any other medications for chronic conditions must be stable for at least 4 weeks before dosing.
Is there any evidence suggesting that this trial's treatment is likely to be safe?
In earlier studies, researchers administered AT132, a gene therapy for X-linked myotubular myopathy (XLMTM), to young children to assess its potential to improve muscle function. Unfortunately, the results revealed serious safety concerns. AT132 was not safe at either of the tested doses. Some children experienced severe complications, and there were fatalities, leading to the study's termination.
Gene therapy like AT132 aims to correct genetic issues by introducing a healthy gene into the body. However, in this case, the treatment proved unsafe. The children who received AT132 are being closely monitored over time for any additional issues and to evaluate their muscle function.
Due to these serious safety concerns, AT132 is not available for public use, and no new participants are being accepted into the study. This underscores the importance of ongoing research and careful monitoring when testing new treatments.12345Why are researchers excited about this study treatment?
Researchers are excited about AT132 because it offers a novel gene therapy approach for treating myotubular myopathy, a condition for which existing treatments mainly focus on managing symptoms rather than addressing the root cause. Unlike current therapies, AT132 delivers a functional copy of the MTM1 gene directly into the patient's cells using an adeno-associated virus, potentially correcting the underlying genetic defect. This approach aims to provide long-lasting benefits from a single intravenous dose, which is a significant improvement over traditional treatments that require ongoing management. Additionally, the use of viral vectors to deliver the therapy represents an innovative method that could pave the way for future advancements in genetic disorders.
What evidence suggests that AT132 might be an effective treatment for myotubular myopathy?
Research has shown that AT132, a gene therapy, may help children with X-linked myotubular myopathy (XLMTM) improve muscle growth and function. In earlier studies, many children who received this therapy needed less ventilator support and demonstrated better movement abilities. The therapy adds a healthy version of the MTM1 gene to the body, enhancing muscle function. However, serious complications and some deaths led to the study's suspension. Despite promising initial results, safety concerns remain significant.
In this trial, participants will receive either a low dose (1.3 × 10^14 vg/kg) or a high dose (3.5 × 10^14 vg/kg) of AT132. The trial aims to assess the safety and effectiveness of these dosing levels.23567Who Is on the Research Team?
Medical Director
Principal Investigator
Astellas Pharma Global Development, Inc.
Are You a Good Fit for This Trial?
This trial is for boys under 5 with X-Linked Myotubular Myopathy (XLMTM) confirmed by a specific gene mutation. They must need breathing support, weigh over 4.8 kg in France, and have no recent surgeries or infections. Those with heart issues, anemia, liver disease, or certain medication use are excluded.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Dose Escalation
Small groups of young children were given different doses of AT132 to determine the best dose for treating the muscle disease.
Pivotal Expansion
Participants were enrolled to confirm the safety and efficacy of resamirigene bilparvovec at a specific dose.
Long-term Follow-up
Participants are monitored for safety and muscle function improvements over a long period after receiving AT132.
What Are the Treatments Tested in This Trial?
Interventions
- AT132
Find a Clinic Near You
Who Is Running the Clinical Trial?
Astellas Gene Therapies
Lead Sponsor
Audentes Therapeutics
Lead Sponsor