Gene Therapy for Tay-Sachs Disease

Overseen By Anupam Sehgal, MBBS

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Dr. Anupam Sehgal

Disqualifiers: Second neurodevelopmental disorder, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a potential gene therapy treatment called TSHA-101 for Tay-Sachs disease, a serious brain condition caused by a missing or faulty enzyme. The main goal is to assess the treatment's safety and patient tolerance. Participants will receive a single dose of TSHA-101 directly into the spine. This trial may suit children under 15 months old diagnosed with the infantile form of Tay-Sachs disease. As a Phase 1/Phase 2 trial, the research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants the chance to be among the first to benefit from this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have allergies or sensitivities to the required immunosuppression regimen, you may not be eligible to participate.

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

Research has shown that the gene therapy treatment TSHA-101 for Tay-Sachs disease is promising in terms of safety. Patients who received TSHA-101 experienced a significant increase in Hex A enzyme activity, which helps break down certain fats in the brain. One patient reached 25% of normal Hex A activity just one month after treatment, five times higher than the safe level, suggesting the treatment is working as intended.

While these results are encouraging, the main goal of the current studies is to assess the safety of TSHA-101 and how well patients tolerate it. So far, patients have tolerated the treatment well, with no severe side effects widely reported in the available data. However, potential participants should always consult a healthcare provider to fully understand the risks and benefits before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Tay-Sachs disease, which primarily focus on managing symptoms, TSHA-101 is a gene therapy that aims to address the root cause of the condition. This treatment is administered directly into the spinal fluid via a one-time intrathecal injection, which allows it to deliver therapeutic genes directly to the central nervous system. Researchers are excited about TSHA-101 because it has the potential to provide a more long-lasting effect by targeting and correcting the genetic deficiency responsible for Tay-Sachs, potentially offering a groundbreaking advancement in treatment.

What evidence suggests that TSHA-101 might be an effective treatment for Tay-Sachs disease?

Research has shown that TSHA-101, the investigational treatment in this trial, may help treat Tay-Sachs disease. One study found that a patient with Tay-Sachs had Hex A enzyme activity at levels five times higher than the threshold where symptoms usually appear. This is significant because people with Tay-Sachs typically lack sufficient levels of this enzyme, leading to the accumulation of harmful substances in the brain. Although no approved cure for Tay-Sachs exists yet, these findings suggest that TSHA-101 might help reduce symptoms by boosting the activity of the missing enzyme. This early data is promising, but further research is needed to confirm its effectiveness and safety. ^{1 2 3 4 6}

Who Is on the Research Team?

Anupam Sehgal, MBBS

Principal Investigator

Queen's University

Are You a Good Fit for This Trial?

This trial is for babies up to 15 months old diagnosed with infantile GM2 gangliosidosis, a neurodegenerative disease. They must have genetic proof of the condition and not be on invasive breathing support or have other major illnesses, allergies to immunosuppressants, another brain development disorder, or issues with sedation.

Inclusion Criteria

I am 15 months old or younger.

I have been diagnosed with infantile GM2 gangliosidosis, confirmed by genetic and enzyme tests.

Exclusion Criteria

I have a neurodevelopmental disorder not related to HEXA or HEXB genes.

I am not allergic to or cannot tolerate the required immunosuppression drugs.

I cannot handle sedation or spinal injections well.

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 intrathecal TSHA-101 gene therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Multiple visits (in-person and virtual)

Long-term follow-up

Participants are monitored for long-term safety and efficacy outcomes

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• TSHA-101

Trial Overview The study tests TSHA-101 gene therapy given through an injection into the spinal canal (intrathecal) to see if it's safe and can be tolerated in treating GM2 gangliosidosis which affects nerve cells due to missing enzyme activity.

How Is the Trial Designed?

Group I: TSHA-101 Experimental Treatment 1 Intervention

Subjects who will receive one-time intrathecal TSHA-101, brain volume based sliding scale for dosage

Who Is Running the Clinical Trial?

Dr. Anupam Sehgal

Lead Sponsor

Trials

1

Recruited

3+

Dr. Anupam Sehgal

Lead Sponsor

Trials

1

Recruited

3+

GlycoNet

Collaborator

Trials

1

Recruited

3+

Taysha Gene Therapies, Inc.

Industry Sponsor

Trials

5

Recruited

60+

Citations

1. ir.tayshagtx.com ir.tayshagtx.com/news-releases/news-release-details/taysha-gene-therapies-announces-positive-initial-biomarker-data

Taysha Gene Therapies Patient 2 with Tay-Sachs disease achieved Hex A enzyme activity 5-fold above the presumed asymptomatic level of 5% of normal identified by ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04798235

NCT04798235 | First-in-Human Study of TSHA-101 Gene ... The primary purpose of the current study is to assess the safety and tolerability of TSHA101 administered via IT injection.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9294361/

Therapeutic Strategies For Tay-Sachs Disease - PMC It affects one in 100,000 live births. Currently, there is no approved therapy or cure. This review summarizes multiple drug development ...

4. ir.tayshagtx.com ir.tayshagtx.com/static-files/81485693-feeb-4868-9b63-d77a974173f1

TSHA-101 in GM2 Gangliosidosis Program Update This presentation includes statistical and other industry and market data that we obtained from industry publications and research, surveys and ...

5. withpower.com withpower.com/trial/phase-2-gangliosidoses-gm2-2-2021-14429

Gene Therapy for Tay-Sachs Disease · Info for Participants What data supports the effectiveness of the treatment TSHA-101 for Tay-Sachs Disease? ... Participants are monitored for long-term safety and efficacy outcomes.

6. biospace.com biospace.com/patient-death-mars-early-data-for-rare-forms-of-gm2-gangliosidosis-for-taysha-gene-therapies

Taysha's Promising Gene Therapy Results Marred by ... After dosing with TSHA-101, the Tay-Sachs patient achieved Hex A enzyme activity of 25% of normal at month 1. That data represents a 5-fold ...