23 September 2021 - - US-based gene therapy company Taysha Gene Therapies, Inc. (NASDAQ: TSHA) has been granted orphan drug designation from the European Commission for TSHA-102, an AAV9-based gene replacement therapy in development for Rett syndrome, the company said.

Rett syndrome is a severe genetic neurodevelopmental disorder caused by a mutation in the X-linked MECP2 gene essential for neuronal and synaptic function in the brain.

Primarily occurring in females, Rett syndrome is one of the most common genetic causes of severe intellectual disability worldwide, with a prevalence of over 25,000 in the United States and European Union.

Patients have normal early development, with symptom onset typically beginning between six to 18 months of age. Rett syndrome is characterized by rapid developmental regression that leads to intellectual disabilities, loss of speech, loss of purposeful use of hands, loss of mobility, seizures, cardiac impairments and breathing issues.

Currently, there are no approved therapies.

TSHA-102 is a self-complementary intrathecally delivered AAV9 gene replacement therapy under development for the treatment of Rett syndrome.

TSHA-102 delivers the MECP2 gene, which includes the novel miRNA-Responsive Auto-Regulatory Element (miRARE), to regulate MECP2 expression in a genotypic-dependent manner on a cell-by-cell basis. The miRARE technology is designed to prevent toxicity associated with overexpression of MECP2.

Positive preclinical data for TSHA-102 in Rett syndrome recently published in Brain provide quantitative evidence of miRARE's ability to exhibit genotype-dependent regulation of MECP2 gene expression on a cell-by-cell basis across different regions of the brain in both wild type and knockout mouse models of Rett syndrome.

TSHA-102 has previously received rare pediatric disease designation and orphan drug designation from the US Food and Drug Administration. Submission of an IND/CTA filing for TSHA-102 is expected in the second half of 2021, with initiation of a Phase 1/2 clinical trial by year-end 2021.

The European Commission grants orphan drug designation for medicines being developed for the diagnosis, prevention or treatment of treat life-threatening or chronically debilitating conditions that affect fewer than five in 10,000 people in the European Union.

Orphan designation in the European Union includes benefits such as protocol assistance, reduced regulatory fees and market exclusivity.