Modern drug discovery approaches take too long, are too expensive, have too many clinical failures and uncertain outcomes. There are many reasons for this unsustainable business model, but primarily, the approaches are not comprehensively holistic.
While the use of human cell lines has become a permanent fixture in drug discovery and development, the lingering issue has been in their inconsistent results.
High-content screening (HCS) is a well-established approach for the multiparametric analysis of cellular events. Since its first introduction more than a decade ago, HCS imaging systems have continually evolved with many improvements enabled to meet user demands of greater flexibility and the growing requirements of assays involving complex cellular disease models.
The case for using more physiologically-relevant cells for modelling disease pathophysiology, for understanding a drug’s mechanism of action, in toxicology/safety testing and in phenotypic drug screening assays is now well accepted.
Large-scale generation of patient-derived induced pluripotent stem cells to accelerate the understanding of disease biology and drug discovery. In 2012, the California Institute for Regenerative Medicine (CIRM) announced its Human iPSC Initiative, an ambitious effort to generate induced pluripotent stem cell (iPSC) lines from 3,000 donors.
The discovery by Yamanaka and Thomson in 2007 that human somatic cells can be reprogrammed to a pluripotent state (ie, induced pluripotent stem cells, iPSCs) has revolutionised cell biology.
Recently, pre-clinical and clinical studies of stem cells in regenerative medicine have demonstrated great promise as treatments for various diseases. Their ability to self-renew and differentiate makes stem cells valuable for both cell therapy and tissue engineering fields, both of which drive the demand for largescale cell expansion.
A recent market survey on stem cells in research and drug discovery showed that despite a significant amount of hype and hope around stem cells, most drug discovery-related efforts today still fall into the category of basic research and the majority of that was directed towards the oncology/cancer disease area. Human-derived stem cells were of greatest interest and the full range of stem cell types were under investigation, with no single stem cell type predominating.
With the failure rates of drug candidates continuing to present phenomenal costs to the pharmaceutical industry, this article discusses how newly emerging induced pluripotent stem cell (iPSC) technologies have the potential to be an effective tool in weeding out low quality candidates early in the process, reducing attrition costs and, ultimately, improving the percentage of new drugs to market.
Stem cells remain a hot topic in academia and industry alike, and with the potential to cause a paradigm shift where many believe in their ability to differentiate into a variety of valuable cell types. They unleashed a screening race using complex cell-based assays to evaluate cytotoxicity profiles of chemical entities, and to ultimately discover novel modulators of cell fate to be used in stem cell-based therapies. A comprehensive small molecule catalogue of modulators is emerging with no obvious value proposition as to their legitimacy towards clinical applications. Almost two decades of experimentation later, have stem cells maintained their pole position at the forefront of contemporary personalised medicine
While the jury is still out in terms of iPS cell technology and its ability to deliver a regenerative therapy or, indeed, contribute to the development of a clinical molecule, this paper argues that the progress by which this technology has been advancing is providing confidence that it will become a breakthrough technology for drug discovery.