Project Summary: Organoid models of Alzheimer’s and Parkinson’s disease using induced pluripotent stem cells (iPSCs) derived from diseased patients have been developed recently as model systems to study disease mechanisms. The 3D organoid model system has certain advantages over the current 2D iPSC derived motor neuron cultures, including the presence of an interstitial compartment, cytoarchitectural organization with synaptic connections and the increased translatability of pre-clinical drug discoveries. Organoids also provides an alternative to animal models for drug screening.

The aim of the project is to develop 3D organoid models of C9orf72-associated amyotrophic lateral sclerosis (ALS) and Frontotemporal dementia (FTD), using patient derived iPSC, to characterize pathogenic phenotypes in motor neurons and cortical neurons. In addition, the strategies of forward genetic screens using CRISPR/Cas9 technology and small compound screening in organoids will be developed to identify suppressors or compounds that counteract the phenotypes.