Speaker:
Dr. Andrea Elser, Applied Stem Cell Sciences Team, Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Abstract:
Rare neuropathies, chemotherapy-induced neurodegeneration and SARM1 activity share common characteristics. NAD-consuming enzyme SARM1 plays a central role in programmed axon death and its loss-of-function has been shown to be protective in subtypes of Charcot-Marie-Tooth disease and Hereditary Spastic Paraplegia. These diseases are characterised by neurite degeneration and mitochondrial defects and currently lack effective therapies. SARM1 inhibitors may provide a much-needed disease-modifying opportunity for certain mechanistic subtypes of rare neurological disorders. To evaluate if SARM1 loss-of-function can protect against neurite degeneration linked to rare neuropathies, we performed arrayed phenotypic CRISPR-Knock-out (KO) screens in wildtype and SARM1-KO human iPSC-derived neurons, focusing on 60 disease-associated genes. In this webinar, we will present in vitro model validation data and how the genetic screen was used to identify rare neuropathies where SARM1 inhibition can be neuroprotective.
