Gene Therapy for SLC6A1 Deficiency

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Emily de los Reyes

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new gene therapy for individuals with SLC6A1 neurodevelopmental disorder, a condition affecting brain development and function. The treatment, AAV9.SLC6A1 Gene Therapy, uses an AAV9 vector to deliver a healthy version of the SLC6A1 gene to the patient. The study aims to determine if this approach can improve symptoms in those with a specific mutation in their SLC6A1 gene. Individuals with this mutation who can actively participate in the study procedures might be suitable candidates for the trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it mentions that if your ongoing treatment creates unnecessary risks for gene transfer, you may be excluded. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

In earlier studies, AAV9.SLC6A1 gene therapy showed promising results in animals. Researchers found that this therapy reduced seizure symptoms in mice and improved their brain activity and behavior. These studies suggest the treatment might be safe in animals, but testing in humans is still necessary to confirm this.

Since this trial is in its early stages, limited safety information exists for humans. Early trials often focus on determining the right dose and identifying side effects. These trials are crucial for understanding how well people tolerate the treatment. Participants in this trial will help researchers learn more about its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for SLC6A1 deficiency, which might include medications to manage symptoms like seizures, AAV9.SLC6A1 Gene Therapy aims to address the root cause of the condition. This therapy uses an adeno-associated virus (AAV9) to deliver a healthy copy of the SLC6A1 gene directly to the patient's cells. This innovative approach could potentially correct the underlying genetic defect, offering a more permanent solution rather than just alleviating symptoms. Researchers are excited because this could lead to significant improvements in quality of life for patients and might even halt the progression of the disease.

What evidence suggests that this gene therapy might be an effective treatment for SLC6A1 deficiency?

Research has shown that a new gene therapy using AAV9/SLC6A1, which participants in this trial will receive, could help treat SLC6A1 deficiency, a disorder affecting brain development. In studies with mice, this therapy greatly reduced seizures and improved unusual brain activity. It also helped correct thinking and behavior problems in these mice. By replacing the faulty gene with a healthy one, the therapy aims to address the main cause of the disorder. These results suggest possible benefits for people, although research in humans is still ongoing. ^{2 3 4 6 7}

Who Is on the Research Team?

Emily de los Reyes, MD

Principal Investigator

Nationwide Children's Hospital

Are You a Good Fit for This Trial?

This trial is for individuals with SLC6A1 neurodevelopmental disorder. Specific eligibility criteria are not provided, but typically these would include age range, disease severity, and overall health status.

Inclusion Criteria

My genetic test shows I have the S295L mutation in the SLC6A1 gene.

I can follow through with tests and treatments as advised.

Exclusion Criteria

Serological evidence of HIV infection, or Hepatitis B or C infection

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Gene Therapy Treatment

Participants receive an AAV9 vector carrying the SLCA1 gene for SLC6A1 neurodevelopmental disorder

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after gene therapy, including changes in VABS, ADOS, and Child Behaviour Checklist scores

3 years

What Are the Treatments Tested in This Trial?

Interventions

• AAV9.SLC6A1 Gene Therapy

Trial Overview The study is testing a gene therapy using an AAV9 vector to deliver the SLC6A1 gene to patients with this specific genetic disorder.

How Is the Trial Designed?

Group I: AAV9.SLC6A1 Gene Therapy Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Emily de los Reyes

Lead Sponsor

Trials

1

Recruited

30+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11785923/

AAV9/SLC6A1 gene therapy rescues abnormal EEG patterns ... Overall, AAV9/hSLC6A1 treatment of neonatal mice showed a strong attenuation of seizure deficits in heterozygous Slc6a1+/– mice and both seizure and behavioral ...

2. jci.org jci.org/articles/view/188703

Gene-replacement therapy in neurodevelopmental disorders AAV9/SLC6A1 gene therapy rescues abnormal EEG patterns and cognitive behavioral deficiencies in Slc6a1–/– mice.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07173153

Gene Therapy for SLC6A1 Neurodevelopmental Disorder It identifies the role of the intervention that participants receive. Types of arms include experimental arm, active comparator arm, placebo ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39589822/

AAV9/SLC6A1 gene therapy rescues abnormal EEG ... Overall, our data demonstrate compelling efficacy when mice are treated at an early development age. We also identified that outside of the ...

5. semanticscholar.org semanticscholar.org/paper/AAV9-SLC6A1-gene-therapy-rescues-abnormal-EEG-and-%E2%80%93-Guo-Rioux/bcd7fadb8b405c5a82741ad9d1e1fd073100e4bf

[PDF] AAV9/SLC6A1 gene therapy rescues abnormal EEG ... AAV9/SLC6A1 gene therapy rescues abnormal EEG patterns and cognitive behavioral deficiencies in Slc6a1–/– mice · 4 Citations · 36 References.

6. jci.org jci.org/articles/view/182235

AAV9/SLC6A1 gene therapy rescues abnormal EEG ... Overall, AAV9/hSLC6A1 treatment of neonatal mice showed a strong attenuation of seizure deficits in heterozygous Slc6a1+/– mice and both ...

7. withpower.com withpower.com/trial/phase-2-slc6a1-7-2025-637cf

Gene Therapy for SLC6A1 Deficiency · Info for Participants This Phase 1 & 2 medical study run by Emily de los Reyes needs participants to evaluate whether AAV9.SLC6A1 Gene Therapy will have tolerable side effects ...