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AAIC 2022 | Discovery and validation of novel drug targets involved in neuroinflammation

Niels Plath, PhD, Muna Therapeutics, Copenhagen, Denmark, discusses the discovery and validation of novel therapeutics for neurodegenerative disorders, such as Alzheimer’s disease (AD). They are combining two platforms to achieve this, firstly, building on a target validation platform. This utilizes genetic information from genome wide association studies and builds on this by also looking at differential gene expression. Using methods such as spatial transcriptomics, they are analyzing human derived brain material in AD patients and comparing them to brain samples from subjects who show resilience to amyloid pathology. It is hoped that studying gene expression in these samples may identify genes that correlate with cellular vulnerability or neuroprotection. These findings are integrated with genetic and protein-protein interaction data to identify targets for novel therapeutics, which can pass through validation platforms. This starts with in vitro studies, then progressing to in vivo trials using human stem cell derived cell lines, which are used in mouse models to replicate the amyloid-beta pathology seen in humans. Concurrently, they are pursuing a structure-based drug design approach where they are collecting structural biology information for particular targets, using techniques such as crystallography. Using this structural information allows for construction of selective and potent compounds and validation of these compounds in experimental settings. This interview took place at the Alzheimer’s Association International Conference (AAIC) 2022 in San Diego, CA

Disclosures

Niels Plath is a full time employee at Muna Therapeutics.