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A cure for Wolfram syndrome could lead to a cure for diabetes and blindness.

Tuesday, January 14, 2014

Patient-based therapeutics part 1

We are taking an unconventional approach to develop therapeutics for Wolfram syndrome. I would call it "patient-based therapeutics." Our extensive molecular characterization of patient cells, especially iPSC-derived cells, has been providing us remarkable insights into the root cause of Wolfram syndrome. Based on these insights, I have been carefully choosing molecular targets and processes for developing therapeutics. These are the endoplasmic reticulum (ER) membrane integrity, ER calcium leakage, calpain-2, and WFS1 gene mutations. 

How we target WFS1 gene mutations? We have started testing genome editing to accomplish this. Genome editing is a process that involves cutting out pathogenic genetic material (i.e., mutations in the WFS1 gene) and replacing it with healthy genetic material. This is a molecular surgery. So I am becoming a molecular surgeon. In short, we are trying to repair a genetic defect in Wolfram syndrome. 

Currently, we are repairing a genetic defect in iPS cells from patients with Wolfram syndrome to see if the molecular surgery can restore the normal function of neural progenitor cells derived from Wolfram iPS cells. This is an important step. When the transplantation of iPSC-derived retinal ganglion cells and beta cells are available in the clinic in the future, we need to repair the genetic defect before the transplantation.