Abstract
Overall Abstract: Cellular programming and reprogramming technology (CPART) has provided a new way to investigate human development and disease. This technology is particularly useful for diseases in which the affected tissue is not available for cell purification and where aspects of cell development are crucial for the pathology. The central nervous system (CNS) is a good example of tissue that falls into this category. Modeling human brain diseases using induced pluripotent stem cells (iPSC) or induced neural cells (iN) has remarkable potential to generate insights into understanding disease mechanisms and opening new avenues for clinical intervention. Researchers now have the opportunity to study human disease in living, developing neural cells that carry the disease-specific genetic variants that are present in the patient. In addition, CPART represents a fresh approach for developing original diagnostic tools and obtaining novel drug candidates for CNS therapy. In order for CPART to be successful/useful, our underlying assumption is that, cellular deficiencies can be measured in vitro, recapitulating the phenotype that is relevant to human brain disease. Success requires that in vitro modeling is robust enough to detect a reliable and statistically meaningful difference between phenotypically normal and abnormal cells derived using CPART. This is particularly important in our view because there could be diseases where the variability of phenotypes will be too large to achieve reliable statistical significance. I will present several potential uses for modeling neurological and psychiatric diseases as well as highlighting areas of caution and opportunities for improvement.