Gene Therapy for Spinal Muscular Atrophy

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Megan Waldrop

Must not be taking: Immune modulatory therapy

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy for spinal muscular atrophy, a condition that weakens muscles over time. The study uses a one-time injection to deliver a specific gene, aiming to improve muscle strength and function. Individuals with confirmed genetic changes related to this condition, whether they can walk 10 meters without help, cannot walk that far, or are not yet walking, might be suitable candidates. The research seeks to determine the treatment's safety and effectiveness. As a Phase 1, Phase 2 trial, it focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it mentions that if you require chronic drug treatment that poses unnecessary risks for gene transfer, you may be excluded. It's best to discuss your specific medications with the trial team.

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

Research has shown that gene therapy for spinal muscular atrophy (SMA) has been studied for safety. For example, onasemnogene abeparvovec, a similar gene therapy, demonstrated a consistent safety record over five years, with no unexpected harmful effects in patients. Common side effects, such as increased liver enzymes and vomiting, have been reported but are usually manageable.

Although some safety concerns have been noted, the benefits of this one-time treatment outweigh them. This is encouraging for those considering joining a trial. While this specific trial uses a different gene, the similar method provides some confidence about its potential safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Spinal Muscular Atrophy (SMA), which often include medications like nusinersen or risdiplam that aim to modify symptoms or slow progression, this gene therapy offers a potentially transformative approach. Researchers are excited because this therapy involves a single intrathecal delivery, directly introducing a functional copy of the SMN1 gene to address the root cause of SMA. This method not only targets the genetic basis of the disease but could also provide long-lasting benefits with just one treatment, setting it apart from existing therapies that require ongoing administration.

What evidence suggests that this gene therapy might be an effective treatment for spinal muscular atrophy?

Research shows that gene therapy holds promise for treating spinal muscular atrophy (SMA). In this trial, participants will receive a single intrathecal delivery of gene therapy. Studies on similar gene therapies, such as onasemnogene abeparvovec, have proven very effective in improving movement abilities and survival rates for SMA types 1 and 2. A review of these studies found that these treatments significantly help patients gain movement skills, such as controlling their head and sitting up. Additionally, data indicate that patients, especially those with more copies of the SMN2 gene, experience better movement abilities after treatment. This evidence suggests that gene therapy could offer hope for those with IGHMBP2-related diseases. ^{6 7 8 9 10}

Who Is on the Research Team?

Megan Waldrop, MD

Principal Investigator

Nationwide Children's Hospital

Are You a Good Fit for This Trial?

This trial is for individuals with genetic confirmation of IGHMBP2-related diseases, such as Spinal Muscular Atrophy or Charcot-Marie-Tooth Disease. Participants can be pre-ambulant, ambulant, or non-ambulant and must be able to perform functional assessments. They cannot have had recent immunizations, infections like HIV/Hepatitis B/C, abnormal blood counts or liver function tests, high AAV9 antibody levels, other systemic illnesses that increase gene transfer risks or require chronic drug treatment.

Inclusion Criteria

I have two confirmed genetic mutations in the IGHMBP2 gene.

I can follow through with tests as my doctor sees fit.

I can walk more than, less than, or exactly 10 meters without help.

Exclusion Criteria

I cannot safely stop my immune therapy for a washout period.

Serological evidence of HIV infection, or Hepatitis B or C infection

My liver isn't working properly, shown by high GGT or bilirubin levels, or abnormal PT/INR.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intrathecal injection of AAV9 vector carrying the IGHMBP2 gene

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Gene Therapy

Trial Overview The study involves a one-time intrathecal injection (into the spinal canal) of an AAV9 vector carrying the IGHMBP2 gene. It's an open-label trial meaning everyone knows what treatment is being given. The goal is to see if this gene therapy can help with conditions related to IGHMBP2 mutations.

How Is the Trial Designed?

Group I: Single Intrathecal Delivery Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Megan Waldrop

Lead Sponsor

Trials

2

Recruited

10+

Alcyone Therapeutics

Collaborator

Trials

1

Recruited

10+

Published Research Related to This Trial

In a phase 3 trial involving 22 infants with spinal muscular atrophy type 1, 59% achieved independent sitting for 30 seconds or longer by 18 months, compared to 0% in an untreated cohort, demonstrating significant efficacy of the gene therapy onasemnogene abeparvovec.

91% of treated patients survived without the need for permanent ventilation by 14 months, highlighting the therapy's potential to improve survival outcomes compared to only 26% in the untreated group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial. Day, JW., Finkel, RS., Chiriboga, CA., et al.[2021]

Onasemnogene abeparvovec, the first approved gene-replacement therapy for spinal muscular atrophy, has been shown to have manageable safety risks, with 101 out of 102 patients experiencing at least one treatment-emergent adverse event (AE) during clinical trials.

Key safety concerns include hepatotoxicity, which resolved with treatment, and transient decreases in platelet counts, while thrombotic microangiopathy (TMA) was noted in postmarketing data, indicating the need for monitoring and potential medical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Trial and Postmarketing Safety of Onasemnogene Abeparvovec Therapy. Day, JW., Mendell, JR., Mercuri, E., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10398149/

The Effectiveness and Value of Treatments for Spinal ... In data from an interim analysis (June 15, 2017), after 576 days, approximately 45% of infants achieved full head control, and 29% were able to sit ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1090379824001272

Outcomes for patients in the RESTORE registry with spinal ... Patients with ≥four SMN2 gene copies treated with onasemnogene abeparvovec monotherapy demonstrated improvements in motor function.

3. hopkinsmedicine.org hopkinsmedicine.org/news/articles/2025/09/novel-in-utero-gene-therapy-holds-promise

Novel In Utero Gene Therapy Holds Promise for Patients ... Researchers say the study findings demonstrate improved motor function in children with SMA who are unable to walk. Read more about this study.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12508997/

Comparative Clinical Outcomes of Nusinersen and Gene ... This comparative effectiveness study examines respiratory and nutritional support, motor function, and survival outcomes in a matched cohort ...

5. nature.com nature.com/articles/s41434-024-00503-8

Gene-based therapy for the treatment of spinal muscular ... Our meta-analysis results indicate that onasemnogene abeparvovec is highly effective in treating SMA types 1 and 2, resulting in the highest ...

6. nature.com nature.com/articles/s41434-025-00529-6

Early life safety profiling of gene therapy for spinal ... The present study examines the safety profile of intravenous onasemnogene abeparvovec gene therapy in a real-world setting.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11492610/

Efficacy and safety of gene therapy with onasemnogene ... Efficacy and safety of gene therapy with onasemnogene abeparvovec in children with spinal muscular atrophy in the DA-CH-region: a population-based ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2329050125000701

Efficacy and preliminary safety assessment of EXG001-307 ... EXG001-307 demonstrated significant therapeutic efficacy, as evidenced by improved survival rates, enhanced weight gain, and restoration of motor functions.

9. neurologylive.com neurologylive.com/view/long-term-data-reinforces-safety-gene-therapy-zolgensma-sma

Long-Term Data Reinforces Safety of Gene Therapy ... Onasemnogene abeparvovec shows a consistent safety profile over five years, with no unexpected late-onset toxicities in SMA patients. Common ...

10. cell.com cell.com/molecular-therapy-family/methods/fulltext/S2329-0501(25)00145-7

Expanding options for spinal muscular atrophy gene therapy The approved gene therapy, while offering the advantage of single-dose administration, has been associated with safety concerns, mostly related ...