Taysha Gene Therapies, Inc. announced new data for multiple preclinical programs and a planned R&D Day, which will be held in June 2021. TSHA-113 for Tauopathies. Taysha is developing tau-specific microRNA (miRNA) shuttles designed to target tau mRNA for all six isoforms found in the human brain and/or mouse brain. TSHA-113 is an AAV9 capsid that packages these miRNA shuttles and is delivered in the CSF for the treatment of tauopathies. In transgenic mouse models carrying human tau, TSHA-113 significantly reduced tau mRNA and protein levels, while demonstrating widespread expression in neurons and glia; Together with previous in vitro findings, these data further validate selective reduction of tau mRNA and protein levels and warrant further preclinical development; An estimated 6.2 million Americans and 7.8 million Europeans are living with Alzheimer's disease. There are an estimated 13,000 patients in the U.S. and Europe affected by MAPT-associated frontotemporal dementia, progressive supranuclear palsy and corticobasal degeneration, which represent a significant commercial opportunity. TSHA-105 for SLC13A5 deficiency: TSHA-105 is a recombinant self-complementary AAV9 vector that expresses the human SLC13A5 protein under the control of a ubiquitous promoter. The drug candidate is being developed for the treatment of SLC13A5 deficiency. In SLC13A5 knockout mice, treatment with TSHA-105 resulted in a significant, sustainable decrease of plasma citrate levels up to three months post-injection compared to age-matched, wildtype controls. TSHA-105 normalized electroencephalogram (EEG) brain activity, reduced the number of seizures, and reduced seizure susceptibility compared to vehicle-treated controls. The company has advanced TSHA-105 into IND/CTA-enabling studies. There are an estimated 1,900 patients with SLC13A5 deficiency in the United States and in Europe. TSHA-106 for Angelman syndrome: TSHA-106 is an intrathecally delivered AAV9 viral vector designed for shRNA-mediated knockdown of UBE3A-ATS, the antisense transcript governing the expression of UBE3A through the paternal allele. In vitro testing in a neuroblast cell line demonstrated consistent knockdown of UBE3A-ATS and a subsequent increase in UBE3A expression across 26 distinct shRNA candidates. Selection of development candidate expected by mid-year. Interim expression and safety data from confirmatory non-human primate (NHP) studies expected by the end of 2021. There are an estimated 55,000 patients with Angelman syndrome in the United States and in Europe. TSHA-112 for Adult Polyglucosan Body Disease (APBD): TSHA-112 is an intrathecally delivered AAV9 viral vector designed for miRNA-mediated knockdown of the GYS1 gene to treat APBD. In preclinical studies, miRNA knockdown of GYS1 induced significant reductions in GYS1 mRNA, GYS1 protein, abnormal glycogen accumulation, and polyglucosan bodies throughout the brain in an APBD knockout mouse model. TSHA-112 decreased neuroinflammatory markers across three distinct mouse models. The company has advanced TSHA-112 into IND/CTA-enabling studies. There are an estimated 10,000 patients with APBD in the United States and in Europe. TSHA-111-LAFORIN for EPM2A and TSHA-111-MALIN for EPM2B for Lafora disease: TSHA-111-LAFORIN and TSHA-111-MALIN are intrathecally delivered AAV9 viral vectors designed for miRNA-mediated knockdown of the GYS1 gene to treat Lafora disease. In preclinical studies, TSHA-111-LAFORIN and TSHA-111-MALIN achieved effective knockdown of GYS1 expression and insoluble glycogen in the Lafora disease laforin and malin mouse models, respectively. Both product candidates decreased Lafora body formation within the brain in their respective mouse models. The company has advanced TSHA-111-LAFORIN and TSHA-111-MALIN into IND/CTA-enabling studies. There are an estimated 700 patients with Lafora disease in the United States and in Europe. TSHA-119 for GM2 AB variant: TSHA-119 is a self-complementary AAV9 vector designed to deliver a functional copy of the GM2A gene to treat GM2 AB variant. In preclinical studies, TSHA-110 caused a significant, dose-dependent reduction of GM2 accumulation at 20 weeks in mice that were dosed intrathecally at postnatal day 1 or at 6 weeks of age. Long-term follow up studies, which include bi-monthly behavioral, as well as biochemical and histological analyses, are currently ongoing. The company has advanced TSHA-112 into IND/CTA-enabling studies. There are approximately 200 patients with GM2 AB variant in the United States and in Europe.