Molecular prosthetics

Dear Friends,

Thank you so much for your support. I hope you are enjoying this beautiful autumn season with your family, and it is time for me to update you about our progress. Today, I’d like to talk about one of the new drugs we are developing as we have made significant progress on this drug in the past few months. I call it “Molecular Prosthetics.”

To provide a cure for Wolfram syndrome, we need to stop the disease progression. A common problem in patients with Wolfram syndrome is a particular type of cell stress, endoplasmic reticulum stress (ER stress), caused by the expression of mutant Wolfram protein (WFS1 protein) produced in patients’ cells. ER stress can ultimately result in dysfunction and death of insulin producing cells, retinal cells, and brain cells. To resolve this issue, we have been developing molecular prostheses that can optimize the structure and conformation of mutant Wolfram protein. If we can restore the structure of mutant Wolfram protein, it should result in resolution of ER stress and reduction of cell death.

I have been working with Amylyx Pharmaceuticals in Cambridge, MA, and NIH/NCATS to evaluate a novel molecular prosthesis in brain cells derived from induced-pluripotent stem cells (iPSCs) of patients with Wolfram syndrome to determine whether this therapeutic has potential to act as a molecular prosthetic/ER stress reducer to treat the disease. We have been getting encouraging results using cells from patients. My goal is to confirm the results in our humanized mouse and rat models of Wolfram syndrome for conducting a clinical trial. This drug seems to be especially beneficial for brain cells. So it is important for us to know if this drug can improve visual acuity and motor function in our rodent models of Wolfram syndrome.

As always, please feel free to contact me with any questions or concerns (urano@wustl.edu). I would like to know what you think and how you feel. Thank you again for your support. Your encouragement keeps me going. I think about our patients every single day. We will decrease human suffering together.

With passion, hope, and gratitude,
Fumi Urano