Pipeline

Thousands of patients are affected by monogenic CNS diseases.

Our deep and sustainable pipeline aims to address this devastating need.

We are advancing our extensive AAV gene therapy pipeline to bring cures to those living with monogenic CNS disease, including for rare and large patient populations. Every one of our gene therapy candidates targets the unique, underlying biology of each indication.

Program

Indication

Discovery

Preclinical

Phase 1/2

Pivotal

Neurodegenerative Diseases

TSHA-120

GRT

Giant Axonal Neuropathy
Preclinical
TSHA-118

GRT

CLN1 Disease
Phase 1/2
TSHA-121

GRT

CLN7 Disease
Phase 1/2

Neurodevelopmental Disorders

TSHA-102

Regulated GRT

RETT Syndrome
Phase 1/2

Genetic Epilepsies

TSHA-105

GRT

SLC13A5 Deficiency
Phase 1/2

GRT: Gene replacement therapy;

TSHA-120

TSHA-120 is a clinical-stage AAV9 gene therapy program being developed for the treatment of giant axonal neuropathy, or GAN, which is a rare autosomal recessive disease of the central and peripheral nervous systems caused by loss-of-function gigaxonin gene mutations. TSHA-120 is an AAV9 self-complementary viral vector that encodes the full length human gigaxonin protein.

TSHA-102

TSHA-102 is being developed for the treatment of Rett syndrome, one of the most common genetic causes of severe intellectual disability. 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.

TSHA-118

TSHA-118 is being developed for the treatment of CLN1 disease, also known as infantile Batten disease, a rapidly progressing rare lysosomal storage disease with no approved treatment. TSHA-118 is a self-complementary AAV9 viral vector that expresses human codon-optimized CLN1 complementary deoxyribonucleic acid under control of the chicken ß-actin hybrid promoter.

TSHA-121

TSHA-121 is an investigational AAV9 intrathecally dosed gene replacement therapy designed to deliver a full-length copy of the CLN7 gene to potentially treat CLN7 disease, a rapidly progressing rare lysosomal storage disease with no approved treatments. The clinical development of the first-generation construct is in collaboration with UT Southwestern (UTSW) and Children’s Health and funded by Children’s Medical Center Foundation.

Publications

Goodspeed, K, et al. Gene Therapy: Novel Approaches to Targeting Monogenic Epilepsies. Frontiers in Neurology. 2022 Jun; https://doi.org/10.3389/fneur.2022.805007

Prasad, S, et al. Accepting the Challenge: Innovative Approaches and Translational Strategies in Gene Therapy Development. Abstract/Presentation. American Society of Gene and Cell Therapy Annual Meeting 2022.

Gray, SJ. Timing of Gene Therapy Interventions: The Earlier, the Better. Mol. Ther. 2016 Jun; 24(6): 1017-1018