Combating Wolfram Syndrome - Fumihiko Urano Sat

Combating Wolfram Syndrome - Fumihiko Urano

Saturday, August 30, 2014

Small molecules and Stem cells

I have realized that I always think about two things, Small molecules for Wolfram syndrome treatment and Stem cell therapeutics for Wolfram syndrome. I call it SWSW.

We are looking for small molecules (i.e., drugs) that can stop the progression of Wolfram syndrome. We have made significant progress in the last 6 months. My team has been collaborating with 5 pharmaceutical and biotech companies to develop drugs for ER stress-related diseases, including Wolfram and Type 1 Diabetes. Although they are not directly involved in the therapeutic development specifically for Wolfram, their advice is precious. They know how to get the approval from the regulatory agencies. They are very kind. They are very sympathetic and give us candid advice. I wish I had a small biotech company focusing on Wolfram syndrome.

I was thinking about stem cell therapies for Wolfram and Type 1 Diabetes while I was waiting for my iced latte at the coffee shop yesterday. Interestingly, I found a director of our newly formed regenerative medicine center there. So I approached her and talked about regenerative medicine and Wolfram. She offered me to serve on the committee of the new regenerative medicine center. I promised that I would help her develop the center. It was a great conversation. I felt that higher power was helping us. I was so grateful.

I hope you will have a wonderful weekend. I am sending kind thoughts toward you.

http://wolframsyndrome.blogspot.com/2014/08/s...cells.html


We have two goals for treating patients with Wolfram syndrome.

1. Halt the progression by drugs.

2. Restore damaged tissues using iPSCs cells modified by the genome editing.

We have created iPSCs (induced pluripotent stem cells) using skin cells from patients with Wolfram syndrome. These cells can be differentiated into any types of cells.

I'd like to briefly summarize my efforts on goal #1 here. To discover drugs, I am currently leading three projects.

1. Looking for FDA-approved drugs that can potentially halt progression of Wolfram syndrome.

We looked for drugs that can protect cell death mediated by the leakage of calcium from the endoplasmic reticulum (ER) to the cytosol. We found four FDA approved drugs and one supplement so far. We are testing these drugs in Wolfram iPSC-derived neural progenitor cells and mouse models of Wolfram syndrome.

2. Looking for a new class of drugs that can protect cell death mediated by endoplasmic reticulum dysfunction.

We have developed a drug screening method to identify drugs that can protect cell death mediated by ER dysfunction. In collaboration with a non-profit organization, we are actively looking for a new class of drugs that can potentially halt the progression of Wolfram.

3. Testing if MANF (mesencephalic astrocyte-derived neurotrophic factor) can suppress the ER calcium leakage-mediated neuronal cell dysfunction in Wolfram iPSC-derived neural progenitor cells.

I will talk about more on MANF some other time. I thought that this was a good biomarker for Wolfram syndrome because expression of this molecule is increased by ER dysfunction. However, the increase of MANF might be an adaptive mechanisms of our cells to cope with abnormal ER function.

http://www.erstress.com/Wolfram-Theraputic_Development.html