Tools & Strategies for Implementing iPSC-based Cell Models for Neurodegenerative Disease Drug Discovery

The ability to derive induced pluripotent stem cells (iPSCs) from differentiated cell types such as fibroblasts, has revolutionized drug discovery for many disease areas including neurodegenerative disease.  Reprogramming patient-derived cells (e.g fibroblasts, PBMCs) into stem cells allows researchers to capture more relevant disease models harboring genotypes for neurodegenerative disease with complex pathology.

By using human iPSCs, it is possible to establish uniform and scalable cell models for drug discovery, without the limitations or invasive procedures associated with using primary cells, or the uncertain translatability of animal models. In combination with precision gene editing through e.g CRISPR/Cas9 technology and directed differentiation of iPSCs to different neuronal cell types, these disease models provide an invaluable tool for accelerating drug discovery.

In this webinar we will give a broad overview of the practicalities of implementing iPSC-based models for neurodegenerative drug discovery by presenting a case study for investigating protein aggregation in iPSC-derived neurons.  The case study highlights how these disease models can be applied for genetic or compound characterization, along with screening applications.  A workflow is also presented to show how SOPs, training and establishment of cell banks can help overcome reluctance implementing complex cell models.

Furthermore, and in-depth overview of gene editing applications and tools will be presented, highlighting how researchers can replicate or remove disease-causing mutations, generate precisely defined knock-out lines and introduce inducible constructs that can drive iPSC differentiation and cell fate. The application of gene edited, iPSC-derived neurons for establishing neuronal co-cultures and cell-based assays will also be discussed.

 

Learning Objectives