Abstract

Discovery of Regenerative Drugs That Modulate Endogenous Progenitor Cells

Jey Jeyakumar, Scientist, Plasticell Ltd

Most of the tissues in the human body are capable of regeneration to maintain their normal function and repair damage caused by injury and disease. We aim to discover small molecules that selectively stimulate this regenerative process. While many molecules with regenerative properties are natural proteins, it is possible to use traditional pharmaceutical drug screening technologies to discover synthetic small molecule modulators of regenerative pathways. For example, a TPO small molecule mimetic, Promacta® (GlaxoSmithKline), was discovered in this way and is now used to treat blood clotting disorders. Progenitor Therapeutics has shown that drugs with regenerative potential can be discovered through screening assays using progenitor cells involved in the maintenance and repair of adult tissues. These cells are relatively rare and usually an integral part of human tissue – they are therefore difficult to isolate in sufficient quantity for screening. To overcome this limitation, we use our unique combinatorial screening technology CombiCult® for the faithful derivation of tissue specific progenitor cells from pluripotent stem cells such as embryonic stem (ES) or induced pluripotent stem (iPS) cells, well-adapted to high throughput screening work flow. Combined with our ProScreen™ technology, IP and know-how, these in vitro-derived progenitor cells are then used to screen drug libraries consisting of diverse set of compounds selected over a broad range of stem cell signaling and regulatory pathways to identify candidates that cause cell regeneration. Using this approach we were able to identify and prioritise drug targets and potential drug leads for a number of preclinical programs/therapeutic areas; the lead program, for the regeneration of articular cartilage to treat osteoarthritis, the regeneration of myelinating oligodendrocytes to treat multiple sclerosis and of muscle to treat Duchenne muscular dystrophy, will be presented.