TSHA-120 / Taysha Gene Therapies - LARVOL DELTA

Intrathecal Administration of scAAV9/JeT-GAN for the Treatment of Giant Axonal Neuropathy (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: National Institute of Neurological Disorders and Stroke (NINDS) | Active, not recruiting ➔ Completed | Trial completion date: Apr 2035 ➔ Apr 2026 | Trial primary completion date: Jun 2030 ➔ Apr 2026

First-in-human • Trial completion • Trial completion date • Trial primary completion date • Gene Therapies • Pain

Intraneural Administration of scAAV9/JeT-GAN Into the Vagus Nerve for Patients With Giant Axonal Neuropathy (GAN) (clinicaltrials.gov) - P1 | N=4 | Recruiting | Sponsor: University of Texas Southwestern Medical Center

New P1 trial • Pain

Broad CNS Biodistribution of AAV9-based Gene Therapies Delivered by Intrathecal Lumbar Puncture in Non-Human Primates (ESGCT 2024) - "During preclinical characterization of investigational gene therapies, biodistribution in NHPs of TSHA-101, TSHA-102, TSHA-105 and TSHA-120 was evaluated after administration by the IT (all products) or ICM (TSHA-102 only) routes. Overall, biodistribution analysis in Taysha’s NHP studies showed that both the IT and ICM routes led to comparable widespread AAV9 distribution throughout the CNS, achieving brain levels of ∼3 – 5 × 105 vg/µg at comparable doses and timing. These findings support the use of lumbar IT administration as an effective, procedurally simple approach for rAAV9 dosing of the CNS."

Gene therapy • Gene Therapies

T2 Hyperintensities in Gracile Tracts of Cervical Spinal Cord in Giant Axonal Neuropathy (GAN). (PubMed, Muscle Nerve) - "The localization of spinal T-2 signal abnormalities to the cervical gracile tracts in GAN patients mirrors the localization of active dying-back axonal degeneration in GAN rodent models and suggests that these T2-signal abnormalities may be used as a surrogate marker of active axonal degeneration in the long tracts of the spinal cord in GAN and possibly other dying-back neurodegenerative diseases involving the spinal cord."

Journal • CNS Disorders • Gene Therapies • Pain

Intrathecal Administration of scAAV9/JeT-GAN for the Treatment of Giant Axonal Neuropathy (clinicaltrials.gov) - P1 | N=14 | Active, not recruiting | Sponsor: National Institute of Neurological Disorders and Stroke (NINDS) | Recruiting ➔ Active, not recruiting | N=21 ➔ 14

Enrollment change • Enrollment closed • Gene Therapies • Pain

Intrathecal Administration of scAAV9/JeT-GAN for the Treatment of Giant Axonal Neuropathy (clinicaltrials.gov) - P1 | N=21 | Recruiting | Sponsor: National Institute of Neurological Disorders and Stroke (NINDS) | Active, not recruiting ➔ Recruiting

Enrollment open • Gene Therapies • Pain

Intrathecal Gene Therapy for Giant Axonal Neuropathy. (PubMed, N Engl J Med) - P1 | "Intrathecal gene transfer with scAAV9/JeT-GAN for giant axonal neuropathy was associated with adverse events and resulted in a possible benefit in motor function scores and other measures at some vector doses over a year. Further studies are warranted to determine the safety and efficacy of intrathecal AAV-mediated gene therapy in this disorder. (Funded by the National Institute of Neurological Disorders and Stroke and others; ClinicalTrials.gov number, NCT02362438.)."

Gene therapy • Journal • Cardiovascular • CNS Disorders • Gene Therapies • Pain • Pediatrics

Intrathecal Administration of scAAV9/JeT-GAN for the Treatment of Giant Axonal Neuropathy (clinicaltrials.gov) - P1 | N=21 | Active, not recruiting | Sponsor: Taysha Gene Therapies, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Gene Therapies • Pain

Taysha Gene Therapies to Host Virtual R&D Day on Lead Clinical Investigational Programs TSHA-120 in Giant Axonal Neuropathy (GAN) and TSHA-102 in Rett Syndrome (GlobeNewswire) - "Taysha Gene Therapies, Inc...discuss updates on TSHA-120, a self-complimentary intrathecally delivered investigational AAV9 gene therapy in clinical evaluation for GAN, and TSHA-102, a self-complementary intrathecally delivered AAV9 investigational gene transfer therapy in clinical evaluation for Rett syndrome....The event will feature collaborator Salman Bhai, MD, Assistant Professor of Neurology at UT Southwestern Medical Center, who will discuss the disease course and biology of GAN and present new data and analyses from the ongoing natural history and interventional trial evaluating TSHA-120. In addition, Taysha leadership will provide a clinical update on the investigational TSHA-102 program, including the initial safety observations of TSHA-102 from the first patient recently dosed in the Phase 1/2 REVEAL trial...More detailed clinical updates on the first patient will be provided in the third quarter of this year."

Clinical data • CNS Disorders • Developmental Disorders

The Optimization of AAV9 Dosage and Fluorescein Concentration in Direct Vagus Nerve Injection to Treat Autonomic Dysfunction (ASGCT 2023) - "We previously reported that a direct vagus nerve injection of AAV9/GAN (scAAV9/JeT-GAN) in combination with lumbar intrathecal (IT) delivery added benefit to the treatment of autonomic dysfunction caused by giant axonal neuropathy (GAN) (ASGCT-2020, Abstract#936)...Using a constant dose of 2.5E11 vg/rat AAV9/GFP, mixed with four different fluorescein concentrations (0.001, 0.002, 0.004, and 0.008) prior to vagal nerve injection into wild type Fischer 344 rats, we identified 0.004% fluorescein as the most optimal concentration to monitor injection fidelity. Taken together, these studies have identified practical parameters for optimal injection of AAV9 directly into the vagus nerve to target critical regions of the autonomic nervous system, which are prerequisite to facilitate the translation of this approach to larger animals and humans."

Pain

Intrathecal Administration of scAAV9/JeT-GAN for the Treatment of Giant Axonal Neuropathy (clinicaltrials.gov) - P1 | N=21 | Recruiting | Sponsor: National Institute of Neurological Disorders and Stroke (NINDS) | Trial completion date: Apr 2030 ➔ Apr 2035 | Trial primary completion date: Jun 2022 ➔ Jun 2030

Trial completion date • Trial primary completion date • Gene Therapies • Pain

Vagus Nerve Delivery of AAV9 to Treat Autonomic Nervous System Dysfunction in Giant Axonal Neuropathy (ASGCT 2022) - P1 | "A Phase I study (NCT02362438) is underway to test the safety of lumbar-injected, intrathecal (IT) delivered scAAV9/JeT-GAN to treat the most severe aspects of GAN...Additional studies are warranted to translate this approach into clinical testing for patients with GAN. Results from these studies are immediately applicable to GAN but may extend to treating a wider variety of neurological diseases."

Gene Therapies • Immunology • Inflammation • Pain • Pediatrics