Gene Therapy for SLC6A1 Neurodevelopmental Disorder

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

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

Study Overview

• Status: Enrolling by invitation
• Conditions: SLC6A1
• Intervention / Treatment: Biological: AAV9.SLC6A1 Gene Therapy

• Study Type: Interventional
• Enrollment (Estimated): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AAV9.SLC6A1 Gene Therapy	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monitoring for the development of unacceptable toxicity.	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.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change the Autism Diagnostic Schedule (ADOS), Module 3, scores from baseline to 3 years following gene therapy.	Scores on the ADOS, Module 3, will be measured by a certified clinical evaluator.	3 years
Change the Vineland Adaptive Behaviour Scale (VABS) scores from baseline to 3 years following gene therapy.	Scores on the Vineland Adaptive Behaviour Scale (VABS) will be measured by a certified clinical evaluator.	3 years
Change the Child Behaviour Checklist scores from baseline to 3 years following gene therapy.	Scores on the Child Behaviour Checklist will be measured by a certified clinical evaluator.	3 years

Collaborators and Investigators

• Sponsor: Emily de los Reyes
• Investigators: Principal Investigator: Emily de los Reyes, MD, Nationwide Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2025
• Primary Completion (Estimated): August 25, 2028
• Study Completion (Estimated): August 25, 2030

Study Registration Dates

• First Submitted: September 8, 2025
• First Submitted That Met QC Criteria: September 8, 2025
• First Posted (Estimated): September 15, 2025

Study Record Updates

• Last Update Posted (Estimated): September 15, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: STUDY00005148

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Due to this being an N = 1 study, providing IPD publicly would likely deidentify the participant.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No