The broad objective of this project is the identification of new medicines for the treatment of Danon disease using a cell-based screening system. To achieve this goal, we use cells derived from stem cells from patients with Danon disease to identify potential medicines. Potential medicines identified in the screen will then be tested on heart cells to confirm that they improve cardiomyocyte function. We will then optimize and generate large quantities of the leading medicines identified through these screens and test them on mice.
Our strategy is based on previously established findings in our lab that Danon stem cell derived heart cells retain key features of the patients from which they were derived. Using cells generated from Danon disease patients, we have confirmed that these cells have impaired function. Initially we plan to screen FDA-approved compounds using this system and then move onto pathway-based small molecule libraries if no FDA-approved compounds are identified. The most promising compounds identified in these screens will then be tested in an established mouse model of Danon disease.
We continue to make progress toward these goals. Currently, we have performed two separate small molecule screens from which we have identified >10 potential compounds of interest. Furthermore, based on pathway analysis done in fibroblasts we have identified one FDA-approved compound for testing in our mouse model.