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

3 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment TSHA-101 for Tay-Sachs Disease?

The research shows that a similar gene therapy using adeno-associated viruses (AAV) increased enzyme activity and temporarily stabilized the disease in patients with Tay-Sachs Disease, suggesting potential effectiveness of TSHA-101. ^{1 2 3 4 5}

Is the gene therapy for Tay-Sachs disease safe for humans?

In a study with two patients, the gene therapy for Tay-Sachs disease was well tolerated, with no treatment-related adverse events reported. This provides early safety data for the therapy in humans. ^{1 2 6 7 8}

How does the treatment TSHA-101 for Tay-Sachs disease differ from other treatments?

TSHA-101 is a gene therapy that uses adeno-associated virus (AAV) to deliver genes directly into the central nervous system, aiming to restore the missing enzyme hexosaminidase A (HexA) activity. This approach is unique because it targets the root cause of Tay-Sachs disease by addressing the genetic deficiency, unlike other strategies that may focus on managing symptoms or slowing disease progression. ^{1 3 6 7 9}

What is the purpose of this trial?

GM2 gangliosidoses are a group of autosomal recessive neurodegenerative diseases characterized by a deficiency of the Hex A enzyme to catabolize GM2, thereby causing GM2 accumulation within cellular lysosomes.Hex A is composed of 2 subunits, α- and β-, coded by the HEXA and HEXB genes, respectively. The primary purpose of the current study is to assess the safety and tolerability of TSHA101 administered via IT injection.

Research Team

Anupam Sehgal, MBBS

Principal Investigator

Queen's University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

1. United States pubmed.ncbi.nlm.nih.gov

AAV gene therapy for Tay-Sachs disease. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

New Approaches to Tay-Sachs Disease Therapy. [2020]

3. England pubmed.ncbi.nlm.nih.gov

A direct gene transfer strategy via brain internal capsule reverses the biochemical defect in Tay-Sachs disease. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Tay-Sachs disease-causing mutations and neutral polymorphisms in the Hex A gene. [2007]

5. England pubmed.ncbi.nlm.nih.gov

Sialidase-mediated depletion of GM2 ganglioside in Tay-Sachs neuroglia cells. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Adeno-Associated Virus Gene Therapy in a Sheep Model of Tay-Sachs Disease. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic Strategies For Tay-Sachs Disease. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

High school Tay-Sachs disease carrier screening: 5 to 11-year follow-up. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Restoration of hexosaminidase A activity in human Tay-Sachs fibroblasts via adenoviral vector-mediated gene transfer. [2007]