MZ-1866

MZ-1866 is a recombinant adeno-associated virus serotype 9 (AAV9)-based gene therapy designed to treat TCF4 deficiency, specifically in Pitt Hopkins Syndrome (PHS). The therapeutic consists of an AAV9 vector carrying a transgene encoding the human Transcription Factor 4 (TCF4) protein. PHS is caused by heterozygous mutations in the TCF4 gene leading to haploinsufficiency and severe neurodevelopmental symptoms. The mechanism of action involves delivering the functional TCF4 gene into neurons via CNS administration, enabling neuronal transduction and expression of TCF4 to compensate for endogenous deficiency. This approach aims to restore normal levels of TCF4 protein in affected cells, thereby improving or reversing disease phenotypes such as intellectual disability, motor delay, speech impairment, seizures, and autism-like behaviors. Preclinical studies have demonstrated that postnatal delivery can prevent or reverse many pathological features in animal models[1][2][3][5][10]. Mahzi Therapeutics is developing this candidate with academic collaborators.

Other names

AAV9-based gene therapy for TCF4 deficiencyAAV-9-based gene therapy for TCF4 deficiencyAAV 9-based gene therapy for TCF4 deficiencyAAV9-TCF4 gene therapyAAV-9-TCF4 gene therapyAAV 9-TCF4 gene therapyAAV9-TCF4 replacement therapyAAV-9-TCF4 replacement therapyAAV 9-TCF4 replacement therapy