I believe we should have three components for the treatment of Wolfram syndrome.
1. Delay the progression of the disease with existing FDA-approved drugs.
This is our current major focus, and we have a rising candidate. We are looking for a simple way to assess the efficacy of this drug in patients and are trying to collect blood samples from patients and their siblings. In parallel, we are also looking for a new group of drugs that can delay the progression of the disease with a company. All of these drugs seem to be related to cellular calcium homeostasis.
2. Enhance the viability of eye cells, brain cells, and pancreatic beta cells.
In Wolfram syndrome, brain cells, eye cells, and beta cells in the pancreas are sensitive to cell stress and susceptible to cell death due to the mutations in the WFS1 gene. We are developing a method to make brain cells, eye cells, and pancreatic beta cells, more resistant to cell stress. We have identified an interesting hormone-like molecule produced in our body called MANF. MANF can make our cells more resistant to cell stress-mediated cell death. We are trying to establish a collaboration with a pharmaceutical company to develop a drug based on our findings.
3. Replace damaged tissues using patients’ skin cells.
As I mentioned in my previous blogs, we have created induced pluripotent stem cells (iPS cells) using skin cells from patients. We are creating brain cells and eye cells using these iPS cells. These cells have been useful to dissect out the mechanisms of the disease and test the efficacy of candidate drugs. We are also replacing a pathogenic WFS1 gene part with a healthy WFS1 gene part in these cells. In the future, we will use these cells for replacing damaged tissues.