I have some exciting updates on our gene therapy development.
The root cause of Wolfram syndrome is pathogenic changes in the WFS1 gene. Therefore, correcting these changes in the WFS1 gene is the best way to treat Wolfram syndrome. We initially used the original CRISPR-Cas9 gene editing technology and then used a newer technology, base editing. Recently, we have started a collaboration with Dr. David Liu’s group at Harvard/MIT (https://www.liugroup.us/) and started using Prime Editing to correct WFS1 gene pathogenic changes in Wolfram syndrome because of safety reasons. Prime Editing is a newer version of gene editing, considered the best gene editing technology available to date. We can now test the technology in high-quality Wolfram syndrome iPS cells and iPSC-derived retinal ganglion cells to develop gene therapy for optic nerve atrophy. We are also creating cortical neurons (brain cells) and inner hair cells (ear cells) from Wolfram iPSCs for developing gene therapy for neurodegeneration and hearing loss.
Furthermore, we created rodent models with pathogenic changes in the Wfs1 gene to test Prime Editing in vivo. We call them humanized Wolfram mice and Wolfram rats. Our ultimate goal is to use this therapeutic modality for our patients, and we are currently establishing a formal collaboration with a newly established biotech.
These are exciting new developments, and we will keep you updated about our progress. Thank you for your continued support and faith in me.
Fumi URANO, MD, PhD – Wolfram Doc