Gene Therapy for Charcot-Marie-Tooth Disease

DS
Overseen ByDawn Scott
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new gene therapy, scAAV1.tMCK.NTF3, for individuals with Charcot-Marie-Tooth Disease Type 1A (CMT1A), which affects leg nerves and causes muscle weakness. The treatment involves a one-time injection into the leg muscles to improve muscle strength and nerve function. Ideal participants have CMT1A, experience ankle weakness, but can still stand on their heels for at least three seconds. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measures its effectiveness in an initial, smaller group.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications, but you cannot participate if you are on ongoing immunosuppressive therapy or have taken it within 6 months before the trial. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the gene therapy under study, scAAV1.tMCK.NTF3, appears safe for humans. Studies have found that patients who received this treatment still had detectable levels in their blood six months later. This indicates that the treatment remains active in the body over time without causing immediate harmful effects.

In earlier studies, those who received the treatment showed significant improvement compared to those who did not, starting about ten weeks after administration. This suggests that the therapy might not only be effective but also generally safe.

While detailed safety data is not provided here, the treatment's progression to this stage indicates it has demonstrated an acceptable level of safety so far. However, as with any new treatment, monitoring for side effects remains important.12345

Why do researchers think this study treatment might be promising?

Unlike other treatments for Charcot-Marie-Tooth disease, which typically focus on symptom management, the investigational treatment scAAV1.tMCK.NTF3 offers a genetic approach. This therapy uses a viral vector to deliver the human NTF3 gene directly into muscle tissue, aiming to promote nerve health and function. Researchers are excited because this gene therapy could potentially address the underlying cause of the disease rather than just alleviating symptoms. The delivery method via intramuscular injection allows targeted treatment, which might lead to more effective and long-lasting results compared to conventional therapies.

What evidence suggests that this gene therapy might be an effective treatment for Charcot-Marie-Tooth Disease?

Research has shown that a new gene therapy, scAAV1.tMCK.NTF3, may help treat Charcot-Marie-Tooth Disease (CMT1A). In earlier studies, patients had measurable levels of the beneficial protein NT-3 in their blood six months after treatment. This therapy improved muscle function and nerve signals in animal studies by enlarging muscle fibers and aiding nerve healing. It also activates mTOR, a process that enhances cell growth and function. These early findings suggest potential benefits for people with CMT1A, but further research is necessary.13456

Who Is on the Research Team?

ZS

Zarife Sahenk, MD., PhD.

Principal Investigator

Nationwide Children's Hospital

Are You a Good Fit for This Trial?

This trial is for individuals aged 18 to 35 with Charcot-Marie-Tooth Disease type 1A (CMT1A) who have a specific gene duplication. Participants should have ankle muscle weakness but can still move against gravity and stand on their heels. They must be able to undergo clinical evaluations and nerve studies, and if sexually active, agree to use contraception.

Inclusion Criteria

I can stand on my heels for more than 3 seconds but have some ankle weakness.
I can participate in clinical evaluations and nerve tests.
Abnormal nerve conduction velocities
See 4 more

Exclusion Criteria

Abnormal laboratory values considered clinically significant (GGT > 3XULN, bilirubin ≥ 3.0 mg/dL, creatinine ≥ 1.8 mg/dL, Hgb < 8 or > 18 g/Dl; WBC > 15,000 per cmm)
Pregnancy or lactation (females subjects will be tested for pregnancy)
Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer
See 11 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a one-time intramuscular injection of scAAV1.tMCK.NTF3 into muscles in both legs

1 day
1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up visits on days 7, 14, 30, 60, 90, 120, and months 6, 9, 12, 15, 18, and 24

24 months
Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

  • scAAV1.tMCK.NTF3
Trial Overview The trial tests a one-time injection of scAAV1.tMCK.NTF3 into the leg muscles of CMT1A patients. It's an open-label study where three subjects will receive this genetic therapy aimed at treating symptoms related to PMP22 gene duplication.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Dose (8.87e11 vg/kg)Experimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials
354
Recruited
5,228,000+

Citations

NCT03520751 | Phase I/IIa Trial of scAAV1.tMCK.NTF3 for ...This clinical trial is an open-label one-time injection dose study in which scAAV1.tMCK.NTF3 will be administered by intramuscular injections into muscles ...
AAV1.NT-3 gene therapy for X-linked Charcot–Marie– ...Measurable levels of NT-3 were found in the serum at 6-month post gene delivery. The outcome measures included functional, electrophysiological ...
Gene therapy to promote regeneration in Charcot-Marie-Tooth ...AAV1.NT-3 gene therapy increases muscle fiber diameter through activation of mTOR pathway and metabolic remodeling in a CMT mouse model. Gene ...
AAV1.tMCK.NT-3 gene therapy improves phenotype in Sh3tc2Ozes et al. report that adeno-associated virus serotype 1 neurotrophin-3 gene therapy improved functional and electrophysiological outcomes ...
Gene therapy to promote regeneration in Charcot-Marie- ...This review surveys the evidence supporting the rationale for AAV1.NT-3 surrogate gene therapy to improve nerve regeneration in CMT1A. The ...
AAV1.NT-3 Gene Therapy for Charcot–Marie–Tooth NeuropathyThe NT-3 gene therapy group performed significantly better starting around 10 weeks compared to PBS controls. We continued to collect functional ...
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