Severe Neurodegenerative, Epileptic Disorders the Target of Taysha Gene Therapies


With numerous targets in CNS diseases and a unique partnership with gene therapy experts at UT Southwestern, Taysha is hoping to fill significant unmet needs.

Taysha Gene Therapies is harnessing gene replacement therapy for the treatment of severe disorders affecting the brain and nervous system, including CLN1 disease and SLC12A5 deficiency, both of which currently have no approved treatments.

The targets are among a number of programs currently being pursued by the company, which has partnered with UT Southwestern’s Gene Therapy Program and its leaders, Steven Gray, PhD, and Berge Minassian, MD.

Gray and Minassian are behind some of the most innovative viral vector research and manufacturing and play a key role in helping advance Taysha’s development efforts. 

Most recently, Taysha announced that its investigational gene replacement therapy for SLC12A5 deficiency—TSHA-105—received orphan drug designation from the European Commission, which followed a similar designation from the FDA.1 The AAV9-based gene therapy, which also received rare pediatric disease designation from the FDA, is intended to treat SLC13A5-related epilepsy, which manifests as persistent seizures and developmental delays in infants soon after birth. 

Preclinical data showed that treatment with TSHA-105 significantly reduced plasma citrate levels, normalized EEG brain activity, and reduced the number of seizures and seizure susceptibility in SLC13A5 knockout mice, providing proof-of-concept and support as the program moves into IND-enabling studies.2 

“We are encouraged by the early evidence of TSHA-105’s disease-modifying approach and believe these designations will help us potentially accelerate the development of this exciting program,” RA Session II, president, founder, and CEO of Taysha, said in a statement.3 “We look forward to working with the FDA to make TSHA-105 available to patients as expeditiously as possible.”

In CLN1 disease, also known as Batten disease, Taysha is in the process of launching a phase 1/2 clinical trial following approval of its investigational new drug application for its therapy TSHA-118, a self-complementary AAV9 viral vector that expresses human codon-optimized CLN1 complementary deoxyribonucleic acid under control of the chicken Beta-actin hybrid promotor. Preclinical studies have demonstrated dose-dependent survival benefits and functional improvements and good tolerability, with support for 5.0x1014 total vg and 1.0x1015 total vg dosing in human trials.4 

In addition, data showed that earlier treatment was associated with better response. As such, Taysha is working with organizations and partners, including Invitae, to support greater access to genetic screening to promote earlier diagnosis of these diseases.5 

“For LSDs [lysosomal storage diseases], there are more than 50 different disorders with overlapping symptoms, making misdiagnosis common,” said Session.5 “Likewise, more than 50% of epilepsies have a genetic basis. When a patient presents with seizures, genetic testing may help identify more than 100 underlying, often rare conditions. We are proud to support these initiatives to help patients gain timely access to natural history studies, clinical trials, and ultimately disease-modifying therapies.”

1. Taysha Gene Therapies receives orphan drug designation for TSHA-105 for the treatment of epilepsy caused by SLC13A5 deficiency from the European Commission. News release. Taysha Gene Therapies. August 25, 2021. 
2. Taysha Gene Therapies announces new data on multiple preclinical programs and upcoming R&D day. News release. Taysha Gene Therapies. April 14, 2021. 
3. Taysha Gene Therapies receives rare pediatric disease and orphan drug designations for TSHA-105 for the treatment of epilepsy caused by SLC13A5 deficiency. News release. Taysha Gene Therapies. January 19, 2021. 
4. Bringing New Cures to Life: CLN1 Disease Investor Day. August 30, 2021. Accessed September 2, 2021. 
5. Taysha Gene Therapies partners with Invitae to enable rapid access to genetic testing and earlier diagnosis of patients with CNS disease for rare and large-market indications. News release. Taysha Gene Therapies. October 6, 2020. 
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