Mahzi Therapeutics has announced that the first patient has been dosed in its Phase I/II UNITE clinical trial evaluating MZ-1866, an investigational gene therapy for the treatment of Pitt Hopkins syndrome, a rare neurogenetic disorder.

The global, multicentre, open-label study is designed to assess the safety, tolerability and preliminary efficacy of a single administration of MZ-1866 in individuals with genetically confirmed Pitt Hopkins syndrome. The condition, estimated to affect between 1 in 34,000 and 1 in 41,000 people, or roughly 8,000 individuals in the United States, is caused by mutations in the TCF4 gene.

Pitt Hopkins syndrome is characterised by a range of severe symptoms, including autism spectrum features, developmental delay, hypotonia, ataxia, breathing abnormalities such as apnea or hyperventilation, significant gastrointestinal complications and, in some cases, epilepsy. MZ-1866 is designed to address the underlying disease biology by delivering functional copies of the TCF4 gene.

Yael Weiss, Chief Executive Officer of Mahzi Therapeutics, described the first patient dosing as a major milestone for both the programme and the company’s transition into a clinical-stage organisation, highlighting the urgent unmet need among patients and families affected by the disorder.

Audrey Davidow, President of the Pitt Hopkins Research Foundation, called the trial launch a historic moment for the community, noting that it reflects years of advocacy and collaboration aimed at advancing meaningful therapeutic options.

MZ-1866 was developed in collaboration with the Muotri Lab at the University of California San Diego. The Phase I/II study has been supported by funding from the California Institute for Regenerative Medicine, a state agency focused on regenerative medicine, stem cell and gene therapy research.

The trial marks an important step in advancing gene therapy approaches for rare neurogenetic conditions and could potentially transform future treatment pathways for individuals living with Pitt Hopkins syndrome.