Thousands of patients are affected by monogenic CNS diseases.

At Taysha, we are focused on developing gene therapies that hold promise to significantly improve outcomes and quality of life for those patients.

Our gene therapy candidates are designed to target the unique underlying biology of CNS diseases. We are laser-focused on advancing our lead clinical program in Rett syndrome.

Lead Clinical Program in Rett Syndrome





Phase 1/2


Rett syndrome

Regulated GRT

REVEAL Adolescent and Adult Study in U.S. and Canada

Rett syndrome

Regulated GRT

REVEAL Pediatric Study in U.S. and U.K.


GRT: Gene replacement therapy

Other Programs

Taysha has a pipeline of early-stage gene therapy programs targeting CNS diseases that we may progress in the future or advance through potential partnerships. We have deprioritized the company sponsored evaluation of certain clinical-stage programs, including TSHA-105 for SLC13A5 and TSHA-118 for CLN1, and are seeking external strategic options to potentially enable further development of these programs.

Please contact us to discuss potential opportunities for partnering and collaborating at .

Rett Syndrome:

A Rare and Devasting Neurodevelopmental Disease

Rett syndrome is a rare progressive neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene encoding methyl CpG-binding protein 2 (MeCP2), which is essential for regulating neuronal and synaptic function in the brain.1 The disorder is characterized by loss of communication and hand function, slowing and/or regression of development, motor and respiratory impairment, seizures, intellectual disabilities and shortened life expectancy.3,5 Rett syndrome progression is divided into four key stages, beginning with early onset stagnation at 6 to 18 months of age followed by rapid regression, plateau and late motor deterioration.3

Rett syndrome primarily occurs in females and is one of the most common genetic causes of severe intellectual disability.3 Currently, there are no approved disease-modifying therapies that treat the genetic root cause of the disease, and there is a significant unmet medical need. Rett syndrome is estimated to affect between 15,000 and 20,000 patients in the U.S., EU, and U.K.4

The Goldilocks Phenomenon

Using a traditional gene therapy approach to treat Rett syndrome presents a distinct challenge. While too little expression of the MECP2 gene causes Rett syndrome, overexpression of MECP2 is harmful as well, as evidenced by MECP2 duplication syndrome, a severe neurodevelopmental disorder.7 The success of a gene therapy approach to treat the underlying cause of Rett syndrome depends on engineering a gene therapy vector that regulates MECP2 expression on a cell-by-cell basis.

We believe TSHA-102, equipped with our novel miRARE technology, can appropriately address this challenge and provide therapeutic benefit.

TSHA-102 for Rett Syndrome:

A Unique Treatment Approach

TSHA-102 is a self-complementary intrathecally delivered AAV9 gene transfer therapy in clinical evaluation for Rett syndrome. Designed as a one-time treatment, TSHA-102 aims to address the genetic root cause of the disease by delivering a functional form of MECP2 to cells in the CNS. The vector is delivered directly to the cerebrospinal fluid via intrathecal administration, which facilitates optimal biodistribution and cell transduction within key regions of the CNS.

miRARE Technology

Because of the risks associated with both under- and over-expression of MeCP2, we have combined high-throughput microRNA (miRNA), profiling and genome mining to create miRNA-Responsive Auto-Regulatory Element (miRARE), our novel miRNA target panel. The miRARE element includes binding sites for endogenous miRNA, which are responsive to MeCP2 levels to prevent overexpression.2,6

By utilizing the miRARE technology, TSHA-102 is designed to mediate levels of MeCP2 in the CNS on a cell-by-cell basis without risk of overexpression. By increasing MECP2 levels in MECP2 deficient cells and maintaining healthy levels of MECP2 output of healthy cells, TSHA-102 has demonstrated the ability to produce and maintain safe transgene expression levels in the CNS.6

Taysha Gene Therapies has secured the following regulatory designations for TSHA-102:

  • U.S. RMAT designation
  • U.S. Fast Track designation
  • U.S. Orphan Drug designation
  • U.S. Rare Pediatric Disease designation
  • EMA Orphan Drug designation
  • U.K. MHRA Innovative Licensing and Access Pathway designation

1. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999;23(2):185-188.

2. Dhungel B, Ramlogan-Steel CA, Steel JC. MicroRNA-regulated gene delivery systems for research and therapeutic purposes. Molecules. 2018;23(7):1500.

3. Gold WA, Krishnarajy R, Ellaway C, Christodoulou J. Rett Syndrome: A Genetic Update and Clinical Review Focusing on Comorbidities. ACS Chem Neurosci. 2018 Feb 21;9(2):167-176. doi: 10.1021/acschemneuro.7b00346. Epub 2017 Dec 15. PMID: 29185709.

4. IRSF; NORD; Amir RE, Van den Veyver IB, Wan M, et al. Rett Syndrome Is Caused by Mutations in X-Linked Mecp2, Encoding Methyl-Cpg-Binding Protein 2. Nat Genet 232:185-188. 1999.

5. Neul JL, Kaufmann WE, Glaze DG, Christodoulou J, Clarke AJ, Bahi-Buisson N, Leonard H, Bailey ME, Schanen NC, Zappella M, Renieri A, Huppke P, Percy AK; RettSearch Consortium. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol. 2010 Dec;68(6):944-50. doi: 10.1002/ana.22124.

6. Sinnet, SE, et al. Engineered microRNA-based regulatory element permits safe high-dose miniMECP2 gene therapy in Rett mice. Brain. 2021 awab182.

7. Van Esch H, Bauters M, Ignatius J, et al. Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males. Am J Hum Genet. 2005;77(3):442-453.