Translational Potential of ex Vivo Gene Therapy in GM2 Gangliosidosis
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: blood sample.
- Who it may be relevant to
- Registry conditions: Tay-Sachs Disease Ganglioside, Sandhoff Disease Ganglioside. Basic parameters: from 5 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
The project aims to optimize and validate this new therapeutic strategy using cells from GM2 patients to evaluate the cross-correction of neurons in vitro by the culture medium of genetically modified myeloid cell lines. The ultimate goal is to demonstrate the potential of CHS-TGEX as an effective treatment in humans for GM2 gangliosidosis.
Detailed description
β-hexosaminidase (β-Hex) is a lysosomal enzyme essential for the degradation of GM2 ganglioside, a glycosphingolipid found mainly in the central nervous system. It is composed of α and β subunits, encoded by the HEXA and HEXB genes, respectively, which combine in different dimers. Mutations in HEXA or HEXB cause Tay-Sachs disease (TSD) and Sandhoff disease (SD), two lysosomal storage disorders that lead to the accumulation of gangliosides in the brain and progressive neurodegeneration. The infantile forms are rapidly fatal, while the late forms progress more slowly, with ataxia, motor weakness, and psychiatric disorders.
No curative treatment exists. Intracerebral gene therapy trials using AAV vectors are underway in children, but uncertainties remain regarding their long-term safety and efficacy. The investigators propose an alternative approach using ex vivo gene therapy on hematopoietic stem cells (HSC-TGEX) with lentiviral vectors integrating the human HEXA and HEXB genes. These modified cells can generate myeloid lineages capable of producing and secreting β-hexosaminidase.
The project aims to optimize and validate this new therapeutic strategy using cells from GM2 patients to evaluate the cross-correction of neurons in vitro by the culture medium of genetically modified myeloid cell lines. The ultimate goal is to demonstrate the potential of CHS-TGEX as an effective treatment in humans for GM2 gangliosidosis.
Interventions
- Biological blood sample
collecting blood sample for various analyses
Primary outcome measures
- Demonstrate effective cross-correction between myeloid cell lines (derived from patients) that have undergone ex vivo gene therapy and in vitro neurons derived from iPSCs from patients with GM2 gangliosidosis. [Time frame: 18 months]
Eligibility criteria
Inclusion criteria
- Proven diagnosis of GM2 gangliosidosis (decreased β-hexosaminidase enzyme activity and/or biallelic pathogenic variants in the HEXA or HEXB gene)
- Age ≥ 5 years
- Blood sample planned as part of treatment
Exclusion criteria
- Opposition from the patient or legal guardians
- Contraindication to venous sampling
- Patient under guardianship or curatorship
- Patient not covered by social security
- Patient covered by AME (State Medical Aid)
- Weight < 25 kg for minor patients
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
France · 1 center
- Département de Neurologie — Paris
Identifiers
NCT: NCT07445490 · APHP260012