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This is a study for the administration of in utero AAV9 transfer in prenatally diagnosed Type I or Type II GM1.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment | Experimental | Participants receive investigational product |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Gene Transfer with an AAV9 Vector Expressing Human ß-galactosidase | Drug | Prenatal administration of an AAV9 Vector Expressing Human ß-galactosidase |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety | Safety (maternal and fetal): adverse and serious adverse events including, but not limited to, death within 24 hours after the procedure, stillbirth, death prior to initial hospital discharge, and serious related or serious unexpected adverse events exceeding those expected with the natural history of treated disease during the first five years of life. This will also include pregnancy outcome. | 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Immunity | Immunity: Assess maternal and neonatal immune responses to the gene transfer vector through measurement of antibody titers to AAV9 serum. | 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Feasibility | Feasibility: successful administration of the full weight-based dose of AAV9 through the fetal umbilical vein and need for halting the intervention prior to administration of a full dose for maternal or fetal indications. | 5 years |
Fetal subject inclusion criteria:
3. Live fetuses at 28 0/7 weeks to 35 6/7 weeks gestation 4. Diagnosis of Type I or Type II GM1 in utero by genetic analyses performed on amniotic fluid, fetal blood, placental tissue, or other samples through chorionic villus sampling (CVS), amniocentesis, or cordocentesis.
Fetal subject exclusion criteria:
1. Fetuses with a concurrent severe structural anomaly, pathogenic genetic diagnosis, or other condition that presents a high risk of fetal mortality.
While all possible congenital or structural anomalies that may be exclusionary cannot be listed, the following will be hard exclusions:
• Cardiac anomaly requiring neonatal surgical intervention
Examples of minor issues that would not be exclusionary include minor genetic or structural anomalies that can be readily treated and would not impact long-term survival, such as:
Maternal subject inclusion criteria:
5. Maternal anti-AAV9 antibodies <1:50. 6. Consents to fetal autopsy in the event of fetal demise
Maternal subject exclusion criteria:
4. Pregnant women with one or more significant comorbidities that would preclude fetal intervention including, but not limited to:
a. Maternal anti-AAV9 antibodies >1:50
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| ID | Term |
|---|---|
| D016537 | Gangliosidosis, GM1 |
| ID | Term |
|---|---|
| D005733 | Gangliosidoses |
| D013106 | Sphingolipidoses |
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008064 | Lipidoses |
| D008052 | Lipid Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D052439 | Lipid Metabolism Disorders |
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| ID | Term |
|---|---|
| D005818 | Genetic Engineering |
| ID | Term |
|---|---|
| D005821 | Genetic Techniques |
| D008919 | Investigative Techniques |
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