Discovery of small molecules to manipulate cell fate in vivo: towards new therapies for degenerative diseases Angela Russell University of Oxford, UK With an increasingly ageing population, chronic diseases including cancers, dementia and heart failure are placing huge demand on society and healthcare services. Regenerative medicine approaches seek to transform healthcare management strategies, improving outcomes for patients suffering from degenerative diseases. Over the past two decades the majority of studies have been focussed on the transplantation of therapeutic cells. Several thousands of clinical trials have been conducted involving cell transplantation and while there have been signs of efficacy in some cases, major hurdles exist to the routine adoption of such therapies in the clinic. Moreover, we now understand that in most cases these cells act not as a cell replacement therapy but rather through the stimulation of endogenous repair pathways already present within the body. This has opened up a whole new avenue of research in the development of agents to directly stimulate these tissue repair and regeneration processes in the treatment of chronic degenerative diseases and injury, negating the need for cell transplantation. The field of drug discovery for regenerative medicine will be introduced and the impact this is beginning to have on the diseases of ageing described. Our own research in the discovery of small molecules to modulate utrophin for the treatment of the muscle degenerative disease, Duchenne Muscular Dystrophy will be described; translation of the first generation utrophin modulator to the clinic and deconvolution of its molecular target and mechanism. Our extension of this approach into regenerative medicine will then be described, exemplified by the discovery of small molecules to stimulate neurogenesis in vitro and in vivo.
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© The Author(s), 2023
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