Microglia models for alzheimer's disease drug screening

Phenovista Biosciences LLC received a $749,700 Project Grant award from the National Institutes of Health's National Institute on Aging under the Aging Research program (CFDA 93.866) for the period February 1, 2021 through August 31, 2021.

The award will support Phenovista's development, validation, and commercialization of a suite of high-throughput, high-content functional assays using human induced pluripotent stem cell-derived microglia models for Alzheimer's disease drug screening. The assays will allow for next-generation in vitro screening of potential Alzheimer's disease therapies targeting microglial functions. The goal is to rank therapies' relative efficacy in modulating microglia, which play a key role in immune surveillance and inflammation in the central nervous system and have been implicated in Alzheimer's and other neurodegenerative diseases.

Abstract

Alzheimer's disease (ad) is a late-onset neurodegenerative disease marked by a progressive loss of memory and other cognitive functions, resulting in profound dementia. Ad is the most common late-onset dementia affecting millions of people in the developed countries of the world and the ad population predicted to reach 130 million by 2050. There has been a concerted effort to identify the mechanism of disease, development of models and therapeutics. In ad and other neurodegenerative diseases, the observations of uncontrolled chronic inflammatory pathology in the CNS and genetic associations of immune pathways have implicated the microglia. The microglia are the key immune cells in the CNS which provide immunesurveillance, secrete inflammatory molecules, and clear cell debris from the extracellular space. In ad, there is an uncoupling of microglial activation and phagocytosis functions suggesting that these cells are targets for ad drug discovery. Recently, human IPS-derived microglia (IMGLS) models have started to become available. Therefore, the overall goal of this multi-phase sbir project is to develop, validate, and commercialize an in vitro high throughput, high content functional suite of ad IMGLS assays with the phenovista's proprietary culture screening system. These assays will allow for a next-generation in vitro system for ranking the relative efficacy of ad microglial based therapies.