22 December 2020 - - Queen's University in Ontario, Canada has received Clinical Trial Application approval from Health Canada for its investigator-sponsored Phase 1/2 trial exploring TSHA-101, US-based gene therapy company Taysha Gene Therapies, Inc's (NASDAQ: TSHA) investigational AAV9-based gene therapy, for the treatment of infantile GM2 gangliosidosis, the company said.

The trial will be a single arm, open-label Phase 1/2 trial evaluating the use of TSHA-101 for the treatment of infants with GM2.

The study will be sponsored by Queen's University and led by Jagdeep S. Walia, MBBS, FRCPC, FCCMG, Clinical Geneticist and Associate Professor Head, Division of Medical Genetics (Department of Pediatrics) at Queen's, and director of Research (Department of Pediatrics), at the Kingston Health Sciences Centre.

GM2 gangliosidosis is a rare and fatal monogenic lysosomal storage disorder and a family of neurodegenerative genetic diseases that includes Tay-Sachs and Sandhoff diseases.

The disease is caused by defects in the HEXA or HEXB genes that encode the two subunits of the β-hexosaminidase A enzyme.

These genetic defects result in progressive dysfunction of the central nervous system. There are no approved therapies for the treatment of the disease, and current treatment is limited to supportive care.

TSHA-101 is an investigational gene therapy administered intrathecally for the treatment of infantile GM2 gangliosidosis.

The gene therapy is designed to deliver two genes HEXA and HEXB driven by a single promoter within the same AAV9 construct, also known as a bicistronic vector.

This approach allows the simultaneous expression of a 1: 1 ratio of the two subunits of protein required to generate a functional enzyme.

It is the first and only bicistronic vector currently in clinical development and has been granted Orphan Drug and Rare Pediatric Disease designations by the US Food and Drug Administration.