Towards a clinical-trial-in-a-dish: Validating an animal product-free stem cell-derived 3D model of Alzheimer’s disease for drug discovery

Worldwide over 50 million people are living with Alzheimer's disease (AD). Currently there is no effective treatment for AD and most clinical trials have so far failed.

This is partly due to the lack of effective in vitro and animal models of AD that could be used in drug discovery prior to testing in humans.

This project aims to address this unmet need by developing an advanced in vitro animal product-free cellular model of AD, which will: Include the two most abundant cell types of the brain, neurons and astrocytes, derived from induced pluripotent stem cells (iPSCs) reprogrammed from somatic cells of heathy controls and people living with AD Recapitulate key AD features such as excessive levels of amyloidβ-42 and hyperphosphorylated Tau Be grown in 3D as this recapitulates the pathophysiology of AD better than cells cultured in 2D.

Because 3D culture relies on the use of the animal-derived product Matrigel, here we will test an alternative to Matrigel by using a novel animal product-free self-assembling peptide hydrogel (SAPH).

Support drug discovery through a high-throughput compatible format The main aims of this project are to: Aim 1: Characterize iPSC-neurons cultured in 3D in Matrigel vs SAPH Aim 2: Develop a 3D model of co-cultured iPSC-neurons and iPSC-astrocytes in SAPH Aim 3: Provide proof-of-concept for the new model in high-throughput drug screening Our long-term vision is to develop an in vitro clinical-trial-in-a-dish model for AD made up of cells derived from iPSCs reprogrammed from somatic cells from patients and that could be used in the future as a platform for pre-clinical drug discovery and personalised medicine.