New Models for Therapeutic Innovation from Japan

Medical innovation has an extraordinary attrition rate. More than the same time reported disastrous results for AMD therapy using autol95% of drug candidates fail to receive final approval for patient care, and to reachmarket the average drug requires a dozen years of research and development at a cost in the billions of dollars (Giri and Bader, 2015). Medical companies are responding by seeking strategies that lower these costs, including a reluctance to invest in less profitablemedications, such as those for rare or complex diseases. One reason costs remain stubbornly high is the dependence on animal models. For many diseases, animal models are the only option, because human samples are difficult to acquire pre-mortem. Even when human cells are available, they often express phenotypes of the disease at late stage. In the case of Parkinson's disease, for example, it has been estimated that approximately 50% of dopaminergic neurons are already lost when patients begin showing symptoms (Bezard et al., 2001). Most experimental therapies tested on human cells at this stage of the disease are unlikely to recover the lost cells, which is whymany Parkinson's patients still await effective treatments. Induced pluripotent stem cells (iPSCs) may provide an alternative model for cheaper and faster drug discovery. Human iPSCs, which were first reported in 2007, describe somatic cells that have been reprogrammed to the pluripotent state fromwhich they can be differentiated into three germ layers (Takahashi et al., 2007). iPSCs revolutionized our understanding of cell identity and revealed the epigenetic mechanism determining this identity. From a medical perspective, iPSCs also launched research into regenerative medicine that had been hamstrung by legislative limitations on the use of embryonic stem cells (ESCs). To date, there exists only one case study of iPSC-based therapy for human patients. In 2014, researchers in Japan transplanted autologous iPSC-derived retinal cells into the eye of a patient suffering from age-related macular degeneration (AMD). Observation one year later showed the transplanted sheet survived well without immune response or adverse proliferation (Mandai et al., 2017). This study was done conservatively, as the same operation on a second patient was cancelled when some irregularities were found in the iPSC clones. Because there is no international consensus on the criteria of safe iPSCs, the authors chose prudence. Comparatively, another article published