SLC6A1
Conditions
Brief summary
This is gene therapy study of an AAV9 vector carrying the SLCA1 gene for SLC6A1 neurodevelopmental disorder.
Interventions
BIOLOGICALAAV9.SLC6A1 Gene Therapy
This is an open-label, single injection study of an AAV9 vector carrying the SLCA1 coding sequence delivered one time through an intrathecal injection.
Sponsors
Emily de los Reyes
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Confirmation of pathogenic mutation S295L in the SLC6A1 gene * Ability to cooperate and complete assessments per determination of the physician and therapists
Exclusion criteria
* Serological evidence of HIV infection, or Hepatitis B or C infection * Diagnosis of (or ongoing treatment) for an autoimmune disease * Presence of a medical condition or extenuating circumstance that, in the opinion of the Sponsor-Investigator, might compromise the participant's ability to comply with the protocol required testing or procedures or compromise the participant's wellbeing, safety, or clinical interpretability * Persistent leukopenia or leukocytosis (WBC ≤ 3.5 K/µL or ≥20.0 K/µL) or an absolute neutrophil count \< 1.5K/µL * Concomitant illness or requirement for chronic drug treatment that in the opinion of the Sponsor-Investigator creates unnecessary risks for gene transfer * AAV9 binding antibody titers \> 1:400 as determined by ELISA immunoassay * Contraindications for intrathecal injection procedure (e.g. spina bifida, meningitis, or clotting abnormalities) * Abnormal laboratory values in the clinically significant range upon normal values in the Nationwide Children's Hospital Laboratory. (GGT \> 78 U/L, Bilirubin ≥ 3.0 mg/dL , Creatinine ≥ 1.8 mg/dL, Hgb \< 8 or \> 18 g/dL; WBC \> 15,000 cells per mL) * Family does not want to disclose participant's study participation with primary care physician and other medical providers. * Bleeding disorder or any other medical conditions or circumstances in which intrathecal (IT) administration of the product or lumbar puncture (for collection of CSF) are contradicted according to local institutional policy * Two consecutive aminotransaminase liver tests \>3 times the upper limit of normal) at screening * Contraindications for MRI scans (e.g., cardiac pacemaker, metal fragment or chip in the eye, aneurysm clip in the brain
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Monitoring for the development of unacceptable toxicity. | 3 years | Unacceptable toxicity is defined as the occurrence of two or more unexpected Grade III or higher treatment-related toxicities that are at least possibly related to the product or procedure, as defined by CTCAE 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change the Autism Diagnostic Schedule (ADOS), Module 3, scores from baseline to 3 years following gene therapy. | 3 years | Scores on the ADOS, Module 3, will be measured by a certified clinical evaluator. |
| Change the Vineland Adaptive Behaviour Scale (VABS) scores from baseline to 3 years following gene therapy. | 3 years | Scores on the Vineland Adaptive Behaviour Scale (VABS) will be measured by a certified clinical evaluator. |
| Change the Child Behaviour Checklist scores from baseline to 3 years following gene therapy. | 3 years | Scores on the Child Behaviour Checklist will be measured by a certified clinical evaluator. |
Countries
United States
Outcome results
None listed