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09.03.17 Livesey lab demonstrate potential of in vitro stem cell model of dementia as drug screening platform

last modified May 17, 2017 02:49 PM
The Livesey lab's model of dementia in a dish, using Down syndrome patients' cells, offers a platform for screening potential drug compounds
09.03.17 Livesey lab demonstrate potential of in vitro stem cell model of dementia as drug screening platform

Images of human iPSC-derived neurons in vitro

Phenotypic Screening Identifies Modulators of Amyloid Precursor Protein Processing in Human Stem Cell Models of Alzheimer's Disease


Brownjohn PW et al. (2017) Stem Cell Reports doi: 10.1016/j.stemcr.2017.02.006.  [ePub ahead of print]

 

Abstract from the paper

Human stem cell models have the potential to provide platforms for phenotypic screens to identify candidate treatments and cellular pathways involved in the pathogenesis of neurodegenerative disorders. Amyloid precursor protein (APP) processing and the accumulation of APP-derived amyloid β (Aβ) peptides are key processes in Alzheimer's disease (AD). We designed a phenotypic small-molecule screen to identify modulators of APP processing in trisomy 21/Down syndrome neurons, a complex genetic model of AD. We identified the avermectins, commonly used as anthelmintics, as compounds that increase the relative production of short Aβ peptides at the expense of longer, potentially more toxic peptides. Further studies demonstrated that this effect is not due to an interaction with the core γ-secretase responsible for Aβ production. This study demonstrates the feasibility of phenotypic drug screening in human stem cell models of Alzheimer-type dementia, and points to possibilities for indirectly modulating APP processing, independently of γ-secretase modulation.

 

Read more about research in the Livesey lab.

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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