Type II diabetes and its associated co-morbidities are a growing global epidemic affecting an esimated 300 million patients worldwide. There currently is an abscence of therapeutic alternatives for halting or reversing disease progression. Furthermore, there is a lack of siutable human cellular models that recapitulate the biology of pancreatic beta-cells and which allow for drug screening activities at scale. AstraZeneca, in collaboration with the laboratory of Professor Douglas Melton (Harvard), are developing protocols to generate iPSC derived, functional, pancreatic beta-cells, at a scale comensurate with industry scale drug discovery. Data presented here demonstrates the succesful application of these protocols and shows the qualification of the generated cells in relation to their biological context. These cells are now being used in screening to generate novel chemical equity and identify new targets. In addition, data is presented that highlights the promise and power of combining precise genome editing (PGE) with iPSC technology to drive target validation, in a human context, with a precison and speed that has hitherto been unachievable. A specific case study is presented relating to Salt Inducible Kinase (SIK) target validation in chronic obstructive pulmonary disease. Here, PGE is applied to determine specific SIK isoform involvement in driving anti-inflamatory phenotypes in iPSC derived macrophages. This approach can be seen as a model for future combination of these two technologies in the target validation space.
Bringing Biologically Relevant Cells to Life - iPSC Technology in Discovery and Safety Assessment
Video Dec 23, 2016
Key concepts discussed in this webinar will include: - Description of the in vitro test systems used to evaluate P-gp and - BCRP inhibition at Sekisui XenoTech and the advantages/disadvantages of these assays - Description of the test system qualification process that takes places prior to offering these assays in definitive studies - Comparison of IC50 values obtained from the different test systems - Comparison of IC50 and Ki values determined with the vesicle test system - How IC50 and Ki values are used to evaluate clinical relevanceWATCH NOW
2nd International Conference on Pharmaceutical Research & Innovations in Pharma Industry
May 30 - May 31, 2019