Tay-Sachs disease, Sandhoff disease Nutritional, Metabolic, Endocrine Disorders of sphingolipid metabolism and other lipid storage disorders
Conditions
Interventions
Single interventional event: neurosurgical delivery of monocistronic rAAV vectors harbouring a and ß human hexosaminidase transgenes by intracranial injection, depositing at 12 sites with supplementa
every 2 months thereafter for 2 years to exclude signs of haemorrhage, systemic infection, immune reactions and encephalitis. CSF testing will be conducted as appropriate but pre-procedure and within
thereafter at intervals alongside MRI (including DTwi and MR spectroscopy), to exclude leukoencephalopathy and incidental lesions before procedure and at day 7
further studies at 3, 6 12 and 24 months to evaluate necrosis and cortical conformation and thickness afterwards. Six monthly neuro-developmental (if relevant) and neuropsychological testing.
Sponsors
Cambridge University Hospitals NHS Foundation Trust (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female infants and young subjects aged 3 months to 18 years 2. GM2 gangliosidosis confirmed by biochemical analysis and molecular analysis of cognate HEXA or HEXB genes in the presymptomatic phase with normal neuromotor development, physical examination and cerebral MR imaging
Exclusion criteria
Exclusion criteria: 1. GM2 activator deficiency 2. Developmental regression or other features of symptomatic GM2 gangliosidosis 3. Clinical or radiological abnormalities of the central nervous system
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| No acute or sub-acute events causing deterioration in neurological function or impaired structural integrity of central nervous system. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end-point criteria on which phase III efficacy studies will be predicated, will compare outcomes in siblings with disease in affected pedigrees with Tay-Sachs and related diseases, as well as population data on the natural course of GM2 gangliosidosis. Procedures include banking of biological samples and interval neuropsychological evaluation. | — |
Countries
Cyprus, Czech Republic, France, Germany, Greece, Israel, Italy, Netherlands, Poland, Portugal, Turkey, United Kingdom
Outcome results
None listed