I always carry a card articulating my strategy to provide a cure for Wolfram syndrome. I think there are four pillars to provide a cure for Wolfram syndrome.
1. Stop the progression of the disease.
We are looking for FDA-approved drugs that can delay the progression of Wolfram syndrome. These drugs are currently used for other indications. We are also developing new drugs specifically designed for Wolfram.
2. Raise Awareness
It is important to raise awareness of Wolfram in health care professionals and the general public. We need a list of doctors who have experience in managing patients with Wolfram.
3. Replace damaged tissues
We are creating eye cells, brain cells, and pancreatic beta cells from patients' skin cells (iPS technology). We are also correcting genetic mutations in these cells (genome editing technology).
4. Protect remaining tissues
We are looking for a trophic factor that can protect remaining brain cells and beta cells from dysfunction and death. MANF and MANF-related molecule that we have identified are good candidates.
Today, I would like to show my gratitude to all the people who keep me going. Who are they? They are patients with Wolfram syndrome and type 1 diabetes. I get around 20-30 emails per day from them. They ask me questions and share their experiences and feelings. I try to respond to every email. They empower me and keep me going. I also thank my colleagues, collaborators, and friends who help me develop therapeutics for Wolfram and raise awareness of the disease. Thank you all.
I would like to briefly outline our current efforts.
1. Develop drugs that can delay the progression of Wolfram syndrome.
As of today, we are focusing on one FDA-approved drug. We are testing the efficacy of this drug in iPS cells from patients and two animal models of Wolfram syndrome. We are also testing two new types of drugs.
2. Making eye cells using iPS cells derived from Wolfram syndrome patients.
As of today, we started seeing eye-like cells in our dishes. I am excited by this. We will keep on differentiating these cells and test the efficacy of our candidate drugs to develop treatments for eye manifestations in Wolfram syndrome.
3. Measuring the levels of disease-progression biomarkers
We have identified two potential disease-progression biomarkers. As of today, we are measuring the levels of these markers in blood samples from patients and control subjects.
4. Correcting genetic mutations using CRISPR technology in cells from Wolfram syndrome patients.
In the future, we need to correct genetic mutations in pancreatic beta cells, brain cells, and eye cells derived from patients' skin cells before they are transplanted. We are performing a "molecular surgery" to replace a mutated segment of WFS1 gene with a normal segment of WFS1 gene in cells from patients.
Here is my concept. Wolfram syndrome is the most difficult form of diabetes. Thus, a cure for Wolfram could lead to a cure for diabetes.
