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Retinal degenerative disorders are a leading cause of the inherited, irreversible and incurable vision loss. While various rodent model systems have provided crucial information in this direction, lack of disease-relevant tissue availability and species-specific differences have proven to be a major roadblock. Human induced pluripotent stem cells (iPSC) have opened up a whole new avenue of possibilities not just in understanding the disease mechanism but also potential therapeutic approaches towards a cure. In this review, we have summarized recent advances in the methods of deriving retinal cell types from iPSCs which can serve as a renewable source of disease-relevant cell population for basic as well as translational studies. We also provide an overview of the ongoing efforts towards developing a suitable in vitro model for modeling retinal degenerative diseases. This basic understanding in turn has contributed to advances in translational goals such as drug screening and cell-replacement therapies. Furthermore we discuss gene editing approaches for autologous repair of genetic disorders and allogeneic transplantation of stem cell-based retinal derivatives for degenerative disorders with an ultimate goal to restore vision. It is pertinent to note however, that these exciting new developments throw up several challenges that need to be overcome before their full clinical potential can be realized.

Publisher Summary This chapter focuses on key documents required for the clinical trial to be conducted, and then on logistical considerations required to be addressed to execute all aspects of the study in an optimum manner. Clinical trials are designed to meet global International Conference on Harmonization good clinical practice (ICH-GCP) standards in almost all countries around the world. The logistical challenges of running multinational trials are therefore considerable, and are likely to be more so in developing regions study protocol includes precise accounts of the design, methodology, and statistical analysis considerations necessary to conduct the trial and analyze data collected. One challenge is to “maintain a balance between brevity and completeness.” If a drug is being considered for more than one indication, or prepared in various formulations, it is possible to create a set of individualized IBs, each one being tailored to a specific indication and/or formulation. The US Food and Drug Administration (FDA) and other regulatory bodies elsewhere in the developed world have been encouraging more trials in developing regions (for diseases that are not of neglect). Chemistry, manufacturing, and controls (CMC) address issues related to drug identity, manufacturing control, and analysis. A successful translation process requires all parties to be familiar with the timelines for securing translation, reviews, and back-translations ready on time. It may be necessary to use some dialects, and to have documents submitted and approved in other languages depending on the target population of the study.

Publisher Summary This chapter focuses on the study management of clinical trials conducted in developing regions of the world. Study management is a complex undertaking in any clinical trial, but considerably more so for large, multisite trials being conducted in developing countries. Cultural differences also need to be considered carefully. Once selected to conduct a specific clinical trial, a CRO has to create its own study team for that trial. This team will include individuals; the precise names used for these positions may differ somewhat from CRO to CRO, but the functions they perform will essentially be the same. The importance of laboratory data becomes extremely clear when one considers the fact that these data account for 70–90 percent of all data contained in marketing approval submissions to regulatory agencies. Although many companies use regional trials in developing regions to support products on a local basis, it is the ability to use locally generated data to support international regulatory submissions that is of greatest interest. Since ICH-GCP is currently less well known in many developing countries, running trials to the satisfaction of international authorities such as the FDA and the European Medicines Agency (EMA) requires huge training efforts for the local CRAs and principal investigators. CROs with global footprints can be very helpful in this regard, since they are knowledgeable about international standards and have been on the ground in developing regions for a number of years.