MZ-1866 AAV9 gene therapy delivered into the brain ventricles for Pitt Hopkins syndrome
Official title: Phase 1/2 First-in-Human Study to Evaluate the Safety, Tolerability, and Efficacy of MZ-1866, an AAV-9 Gene Therapy Delivered by Intracerebroventricular Injection to Participants With Pitt Hopkins Syndrome
Run by Mahzi Therapeutics · NCT07135050 · Data updated 2026-11-12
This will test a single intracerebroventricular dose of MZ-1866 AAV9 gene therapy in children and adults with Pitt Hopkins syndrome to see if it is safe and tolerable.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Ages | 2 Years to 25 Years |
| Sex | All |
| Enrollment | 12 (estimated) |
| Sponsor | Mahzi Therapeutics Industry-sponsored |
| Locations | 4 sites (Oakland, California and 3 other locations) |
| Status | Recruiting |
| Started | December 19, 2025 |
| Main results expected | March 2029 |
| Study ends | July 2029 |
| Registry record updated | July 31, 2026 |
| Trial ID | NCT07135050 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Ideal candidates are children or adults with a confirmed pathogenic or likely pathogenic TCF4 mutation and clinical features of Pitt Hopkins who are medically able to undergo an intracerebroventricular procedure and attend follow-up visits.
✕Probably not a fit
Patients with very large deletions that include TCF4 (>12 Mbp), other unrelated genetic or medical conditions that would confound outcomes, or structural CNS abnormalities that make ICV injection unsafe are unlikely to benefit.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This Phase 1/2 study gives a single intracerebroventricular (ICV) dose of MZ-1866, an AAV9-based gene therapy designed to address TCF4 dysfunction in Pitt Hopkins syndrome. Participants are followed with regular safety monitoring including physical exams, laboratory tests, ECGs, and adverse event reporting. Neurodevelopmental assessments and caregiver diaries/questionnaires are used periodically to track changes in behavior and development. Enrollment requires a pathogenic or likely pathogenic TCF4 mutation and excludes individuals with large deletions or CNS conditions that prevent safe ICV delivery.
Why it matters
Potential benefit: If successful, this approach could reduce key neurological symptoms and improve development and daily functioning for people with Pitt Hopkins syndrome.
How similar studies have gone: AAV9 gene therapies have shown benefit in other genetic neurological disorders (for example spinal muscular atrophy) and preclinical work supports ICV delivery, but using MZ-1866 for Pitt Hopkins is a novel, early-stage approach.
Who can join: the full rules
Show full inclusion / exclusion criteria
Inclusion Criteria: * The participant has a TCF4 gene mutation confirmed as "pathogenic" or "likely pathogenic" by whole exome sequencing, whole genome sequencing, gene panel, single gene testing, or microarray, performed at an accredited laboratory * Clinical phenotype consistent with Pitt Hopkins Syndrome, in the opinion of the investigator * The participant, or the participant's parent or legal guardian, is willing to provide access to prior medical records for the collection of demographics and diagnostic and treatment history Exclusion Criteria: * A deletion that includes the TCF4 gene that is over 12 Mbp in size * Another genetic mutation or clinical comorbidity not associated with Pitt Hopkins Syndrome that could potentially confound interpretation of the study data * A central nervous system structural or vascular abnormality that is a contraindication to the ICV administration procedure, including but not limited to: signs or symptoms of increased intracranial pressure, history of a space-occupying lesion, or presence of a ventricular shunt that would preclude ICV procedures or safety assessments, or increase risk to the participant * Not able to receive prophylactic corticosteroids due to a medical contraindication or participant has a history of a condition that could worsen with corticosteroid therapy as assessed and determined by the Investigator * Not able to undergo MRI procedures * Cannot be anesthetized for the ICV injection
Where it's running
-
UCSF Benioff Children's Hospital Oakland
Oakland, California, United States Recruiting -
Children's Hospital Colorado
Aurora, Colorado, United States Recruiting -
Rush University Medical Center
Chicago, Illinois, United States Recruiting -
Sheba Medical Center
Tel HaShomer, Israel Recruiting
Study contacts
- Study coordinator: Emily Radomile
- Email: clinicaltrials@mahzi.com
- Phone: 1-844-446-2494
Similar studies
Other studies for the same condition or treatment. Recruiting studies are listed first.
-
Testing vorinostat for safety and potential benefit in Pitt Hopkins syndrome
This trial will try daily oral vorinostat at two dose levels and placebo to see if it is safe and helps children and young adults (ages 3–21) with Pitt Hopkins syndrome.
-
Registry for patients with rare diseases
This study is creating a central registry for people with rare diseases to help connect them with researchers and improve treatments.
How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.