Disease Modeling

    iPSCs for Development of Gene and Drug Based Therapeutics

      There are now numerous examples from animal models, and a few from human clinical trials, of successfully mitigating an inherited eye disease with a gene-replacement or gene silencing strategy. A sobering aspect of this otherwise exciting progress is the extremely slow pace of moving these therapies from a “proof of concept” stage in animals to a fully approved treatment that is available to anyone who needs it.

      Some diseases might be so rare in the population that it is not economically possible to bring a treatment through the regulatory gauntlet and into clinical availability. Additionally some genes will have a very narrow range of therapeutic “dose” such that overexpression could be as harmful as underexpression.

      To decrease the time between gene discovery and clinical trial, our lab is focused on using patient specific induced pluripotent stem cells (iPSCs) generated from a patient’s own skin to interrogate disease pathophysiology and test the efficacy of novel therapies.

      A summary of this strategy is depicted below.

      Disease modeling.jpg

      1) Blood and 3mm skin biopsies collected from patients with inherited retinal degenerative disease are used to identify the patients disease causing gene/mutations and generate iPSCs respectively.

      2) Patient specific iPSCs are differentiated into retinal tissue and initially used to confirm disease causing gene/mutations and interrogate disease pathophysiology.

      3) Patient specific retinal tissue is used to test novel genome editing, gene augmentation, and drug based therapeutics for ability to mitigate disease phenotype.