Taysha Gene Therapies announced that it has received rare paediatric disease designation and orphan drug designation from the US Food and Drug Administration (FDA) for TSHA-102, an AAV9-based gene therapy in development for the treatment of Rett syndrome. Taysha anticipates that it will submit an Investigational New Drug (IND) application for TSHA-102 to the FDA in 2021.

 “Patients with Rett syndrome are currently managed with symptomatic treatments as there are no therapies approved to treat the underlying cause of disease,” said Berge Minassian, Chief Medical Advisor of Taysha and Chief of Pediatric Neurology at the University of Texas Southwestern Medical Center (UT Southwestern). Dr Minassian is credited with describing the CNS isoform of the MECP2 gene which is responsible for neuronal and synaptic function throughout the brain. “Gene therapy offers a potentially curative option for patients suffering with Rett syndrome.”

Rett syndrome is caused by mutations in the MECP2 gene. TSHA-102 is designed to deliver a healthy version of the MECP2 gene as well as the miRNA-Responsive Auto-Regulatory Element, miRARE, platform technology to control the level of MECP2 expression.

“TSHA-102 represents an important step forward in the field of gene therapy, where we are leveraging a novel regulatory platform called miRARE to prevent the overexpression of MECP2. In collaboration with Sarah Sinnett to develop miRARE, our goal was to design a regulated construct that allowed us to control MECP2 expression to potentially avoid adverse events that are typically seen with unregulated gene therapies,” said Steven Gray, Chief Scientific Advisor of Taysha and Associate Professor in the Department of Pediatrics at UT Southwestern.”

The FDA defines a rare paediatric disease as a serious or life-threatening disease in which the disease manifestations primarily affect individuals aged from birth to 18 years. Orphan drug designation is granted by the FDA Office of Orphan Products Development to investigational treatments that are intended for the treatment of rare diseases affecting fewer than 200,000 people in the US.

Rett syndrome is one of the most common genetic causes of severe intellectual disability worldwide. It is an X-linked disease that primarily occurs in females, but it can be seen very rarely in males. It is usually recognised in children between six to 18 months of age as they begin to miss developmental milestones or lose abilities they had developed. Individuals with Rett syndrome also show symptoms that include loss of speech, loss of purposeful use of hands, loss of mobility, seizures, cardiac impairments, breathing issues and sleep disturbances.