Rare Diseases and Orphan Drugs

Biography

Biography: Alan B Moy

Abstract

Pluripotent stem cells represent a potential regenerative medicine for several orphan diseases because the cells exhibit broad plasticity. Induced pluripotent stem cells (IPSC) have the potential to serve as an autologous as well as an allogeneic cell therapy. However, IPSC therapy has not yet been fully realized because the IPSC reprogramming methods have historically required viral gene delivery and oncogenes in order to create a final IPSC product. Non-integrating IPSC reprogramming approaches like self-replicating ribonucleic acid and Sendai virus have been developed to reduce the tumorgenicity risk. However, these reprogramming methods still pose significant costs and oncogenic risk because they utilized the oncogenes, c-Myc and Lin28. Episomal reprogramming is a safe reprogramming approach to produce clinical-grade IPSC therapies. However, the reprogramming efficiency of episomal vectors has been inefficient and has required c-Myc and Lin28 to compensate for the low efficiency. We have developed a combinatorial reprogramming approach of small molecules and a novel episomal construct that is free of c-Myc and Lin28. The combinatorial approach significantly increased the reprogramming efficiency. Further, the reprogramming method also utilized a well-defined tissue cultured media that is feeder-free, xeno-free and matrigel-free. This combinatorial reprogramming approach is now poised to transition into GMP operations, which would satisfy regulatory requirements. The opportunity now exists to develop clinical-grade and safe IPSC for a variety of orphan diseases.