Taysha Gene Therapies Announces Publication of Positive Preclinical Data for TSHA-104 Demonstrating Therapeutic Potential in SURF1-associated Leigh Syndrome in Journal Molecular Therapy: Methods & Clinical Development
September 15, 2021 at 07:00 am EDT
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Taysha Gene Therapies, Inc. announced publication of new preclinical data for TSHA-104 in SURF1-associated Leigh syndrome in Molecular Therapy: Methods & Clinical Development. SURF1 deficiency is a monogenic mitochondrial disorder that is the most common cause of cytochrome c oxidase deficient Leigh syndrome, a rapidly progressive neurological disorder that leads to degeneration of the CNS. Leigh syndrome typically presents in the first year of life and is characterized by progressive loss of mental and movement abilities that can result in death in early childhood. Approximately 10-15% of people with Leigh syndrome have a SURF1 mutation, and the estimated prevalence of SURF1 deficiency is 300 to 400 patients in the United States and European Union. There are currently no approved therapies to treat SURF1-associated Leigh syndrome. A one-time intrathecal injection of TSHA-104 resulted in codon-optimized human SURF1 expression in multiple relevant brain and spinal cord regions in SURF1 knockout mice. A combination of intrathecal and intravenous delivery did not provide any benefit over intrathecal delivery alone, supporting continued use of intrathecal administration. TSHA-104 increased mitochondrially encoded cytochrome c oxidase 1 (MT-CO1) abundance four weeks post-injection in the CNS and peripheral tissues and increased COX1 activity in brain and muscle in a dose-dependent manner. Biochemical COX activity correlated with histological COX content level, supporting regional COX activity. Following exhaustive exercise-induced lactic acidosis TSHA-104 was able to rescue elevated lactate levels in SURF1 knockout mice dose-dependently. The safety profile assessed by non-GLP (Good Laboratory Practice) evaluation in wild-type mice using a similar dosing regimen determined no associated toxicity risks or severe tissue damage detected up to one year post-injection. Collectively this proof-of-concept study demonstrates TSHA-104 can safely and sufficiently rescue mitochondrial dysfunction in SURF1 knockout mice, supporting further translational development for the treatment of SURF1-associated Leigh syndrome. TSHA-104 is an AAV9-based gene replacement therapy encoding the human SURF1 protein that is administered intrathecally for the treatment of SURF1-associated Leigh syndrome. TSHA-104 has been granted Orphan Drug and Rare Pediatric Disease designations by the FDA.
Taysha Gene Therapies Inc is a clinical-stage biotechnology company, which is focused on advancing adeno-associated virus (AAV)-based gene therapies for severe monogenic diseases of the central nervous system. The Companyâs lead clinical program, TSHA-102, is in development for the treatment of Rett syndrome, a rare neurodevelopmental disorder. The Company is evaluating TSHA-102 in the REVEALPhase I/II adolescent and adult clinical trial, which is a first-in-human, open-label, randomized, dose escalation and dose-expansion, multicenter study evaluating the safety and preliminary efficacy of TSHA-102 in female patients aged 12-years and older with Rett syndrome. It has acquired a worldwide right to a clinical-stage, intrathecally dosed AAV9 gene therapy program, TSHA-120, for the treatment of giant axonal neuropathy (GAN). It received orphan drug designation from the European Commission for TSHA-120 for the treatment of GAN.
Taysha Gene Therapies Announces Publication of Positive Preclinical Data for TSHA-104 Demonstrating Therapeutic Potential in SURF1-associated Leigh Syndrome in Journal Molecular Therapy: Methods & Clinical Development
TAYSHA GENE THERAPIES, INC. 
