Pipeline

MZ-1866 is a gene therapy being developed to treat Pitt Hopkins Syndrome, a disorder caused by de novo mutations in a transcription factor called TCF4. Affected individuals present with a combination of autism, developmental delay, hypotonia, ataxia, apnea/hyperventilation, gastrointestinal issues and less frequently epilepsy.

Mahzi, in collaboration with UCSD, has developed an AAv9 based gene therapy. MZ-1866 is a novel AAV9-TCF4 gene replacement therapy, produced by inserting TCF4 isoform B (the longest known isoform and one of the most abundant brain isoforms) into an AAV9 expression cassette under the regulation of multimer E box sequences. Mahzi is currently planning a Phase 1-2 Clinical Trial.

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Letter to the Community/FAQs

Presents as a severe form of epileptic encephalopathy at birth – WOREE (WWOX related epileptic encephalopathy) and a slightly less severe form which presents around the age of 10-12 months – SCAR12 (spinocerebellar ataxia 12). Both forms are characterized by refractory epilepsy, global developmental delay and cognitive impairment.

These WWOX related diseases are caused by mutations in WWOX (WW domain containing oxireductase), Inherited in an autosomal recessive or compound heterozygous manner.

Mahzi in collaboration with the Aqeilan lab at the Hebrew University, Jerusalem, is developing an AAV9 based gene replacement approach to treat these diseases.

Children present at the age of 6 months – 4 years with a combination of refractory epilepsy, global developmental delays, speech and motor delays, intellectual disability, behavioral problems, autism, photosensitivity, and regression (loss of milestones).

The disorder is caused by mutations in the CHD2 gene that provides instructions for making Chromodomain DNA Helicase Protein 2, an epigenetic regulator.

Mahzi, in collaboration with the Ulitsky lab at the Weizmann Institute of Science, Rehovot, is developing an ASO approach for the treatment of CHD2 deficiency.