Gene Therapy for SLC6A1 Neurodevelopmental Disorder

Official title

Phase I/II Intrathecal Gene Delivery Clinical Trial of scAAV9.P546.SLC6A1 for SLC6A1 Neurodevelopmental Disorder

Overview

This is gene therapy study of an AAV9 vector carrying the SLCA1 gene for SLC6A1 neurodevelopmental disorder.

Interventions

• Biological AAV9.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.

Primary outcome measures

• Monitoring for the development of unacceptable toxicity. [Time frame: 3 years]

Secondary outcome measures (3)

• Change the Autism Diagnostic Schedule (ADOS), Module 3, scores from baseline to 3 years following gene therapy. [Time frame: 3 years]
• Change the Vineland Adaptive Behaviour Scale (VABS) scores from baseline to 3 years following gene therapy. [Time frame: 3 years]
• Change the Child Behaviour Checklist scores from baseline to 3 years following gene therapy. [Time frame: 3 years]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Nationwide Children's Hospital — Columbus

Publications

• Samanta D. SLC6A1-Related Neurodevelopmental Disorder: A Scoping Review of Clinical Features and Emerging Therapeutic Strategies. Pediatr Neurol. 2026 Jul;180:155-170. doi: 10.1016/j.pediatrneurol.2026.04.014. Epub 2026 May 5. PMID 42173049

Identifiers

NCT: NCT07173153 · STUDY00005148

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗