Preclinical Data Now Available on TSHA-102 for Rett Syndrome

In a recent news release, gene therapy company Taysha Gene Therapies (“Taysha”) shared the publication of preclinical data on the company’s drug candidate, TSHA-102. Currently, Taysha is exploring TSHA-102 as a potential treatment for patients with Rett syndrome. The promising preclinical data suggests that the therapy’s ability to regulate MECP2 expression could potentially reverse Rett syndrome progression. Check out the study findings published in Brain.

Rett Syndrome

Rett syndrome is a rare neurological disorder which mostly affects young females. While Rett syndrome was once thought to exist on the autism spectrum, recent research recognizes its underlying genetic cause. Specifically, MECP2 gene mutations on the X chromosome cause this severe disorder. In many cases, it occurs as a spontaneous mutation rather than an inherited mutation. Typically, males with this mutation do not live past birth. Many females with Rett syndrome are also unable to live independently. While patients often develop normally for the first 6-12 months of life, symptoms associated with Rett syndrome often appear between 12-18 months. Symptoms include:

  • Microcephaly
  • Slowed brain growth
  • Low muscle tone
  • Poor sucking ability
  • Irritability
  • Scoliosis (abnormal spinal curvature)
  • Irregular heartbeat
  • Uncoordinated breathing
    • Note: This may consist of forcefully exhaling air or saliva, hyperventilating, or swallowing air.
  • Loss of language skills and abilities
  • Social anxiety
  • Sleep disturbances
  • Seizures
  • Loss of purposeful hand function
    • Note: Patients with Rett syndrome may also show compulsive hand movements, such as wringing or clapping.
  • Poor muscle coordination and/or mobility loss

Learn more about Rett syndrome.


According to Taysha, TSHA-102 is:

constructed from a neuronal specific promoter, MeP426, coupled with the miniMECP2 transgene, a truncated version of MECP2, and miRNA-Responsive Auto-Regulatory Element, or miRARE, our novel miRNA target panel, packaged in self-complementary AAV9.

Prior to the development of TSHA-102, researchers found it difficult to regulate transgene expression. However, years ago, Dr. Steven Gray, PhD, created the miRARE approach to manage this. Now, TSHA-102 offers a built-in self-regulatory feedback loop mechanism to help regulate MECP2 expression on a cell-by-cell basis. This helps overcome potential issues such as various genetic phenotypes, MECP2 toxicity related to genetic overexpression, and potential mosaicism. In the past, for example, MECP2 overexpression has been toxic, even fatal. Thus, the miRARE regulatory system allows for TSHA-102 to not only be effective, but to reduce mortality and improve survival rates.

Within this study, researchers used mice models of Rett syndrome. Altogether, these mice models were between 4-5 weeks old. Researchers administered TSHA-102 intrathecally (into the spinal theca). Once administered, TSHA-102 improved survival rates by 56% in knockout mice. Knockout mice are those who scientists genetically altered to “knock out,” or inactivate, a specific gene. This regulated MECP2 treatment shows promise over unregulated MECP2, which often relates to gene overexpression. Thus, TSHA-102 has the opportunity to fulfill an unmet need in the Rett syndrome sphere.

Altogether, Tasha hopes to use this data to both file an Investigational New Drug (IND) application, as well as initiate a Phase 1/2 clinical trial.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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