TS-002279 — What: gene therapy for pediatric epileptic encephalopathy resultant from mutations in SLC6A1 gene Six new gene replacement products New shRNAs for gene knockdown New delivery route and dosing ranges Why: pediatric epileptic encephalopathy Current treatment is limited to symptomatic treatment, primarily by use of antiepileptic drugs How: single stranded AAV serotype 9 that will provide a wildtype copy of SLC6A1 to address haploinsufficiency resultant from mutations in one copy of the SLC6A1 gene Delivered through cerebrospinal fluid (CSF) via injection

TS-002177 — Researchers at Nationwide Children's Hospital are in the process of developing an Adeno-Associated Virus (AAV) gene therapy for the Eukaryotic Initiation Factor 2B complex (EIF2B5) related Vanishing White Matter Disease (VWM), an inherited pediatric leukodystrophy disease resulting from autosomal recessive mutations in the five subunit genes of EIF2B5. VWM deteriorates the central nervous system’s white matter which affects the brain’s communication and function. Common symptoms include spasticity, ataxia, hypotonia, speech issues, dysphagia, vision and hearing impairments along with cognitive deficits. The research team is evaluating the CSF delivery of AAV serotype 9 that will target astrocytes which are central in VWM pathology in order to constitute potential therapeutic targets. The AAV vectors will provide wildtype copies of EIF2B5 to address the loss of function resultant from mutations.