END WOLFRAM, END DIABETES, END ALS

I was watching the video that our friend and patient, Alejandro, was doing an ice bucket challenge.

Photo of Dr. Fumihiko Urano

Dr. Fumihiko Urano

This project originally started for ALS. So I was checking the ALS-related websites and found the following youtube video. As most of you know, ALS (amyotrophic lateral sclerosis) is a neurodegenerative disease, leading to the progressive degeneration of the motor neurons. As a result, patients with ALS may become totally paralyzed.

In these video series, many friends of Mr. Hiro Fujita, who has lost his voice due to ALS, read his messages. The project is called “END ALS.” He was in the advertising business. So many celebrities read his messages. One of his messages was toward his mother. I would probably say the same word. There is an English caption in each video. He said, “Mom, Thank you.”

He has a website, END ALS. He often uses the word, “HOPE.” What do we need to help our patients suffering from life-threatening diseases? How can we create HOPE? Let’s think about the basics.

1. Make correct diagnosis and refer them to the best specialists.

2. Develop therapeutics to stop the progression.

3. Replace damaged tissues.

These three should happen simultaneously. We need all of these. I want to END WOLFRAM, END DIABETES, END ALS, and…

I hope you will have a wonderful day. Thank you for reading this blog. Thank you for your supports. Thank you, thank you, thank you.

Thank you again, and Regenerate to Beat Degeneration.

Posted: 01 Sep 2014 05:53 AM PDT

I was surprised and glad to see that our patient and friend, Alejandro, was doing an ice bucket challenge for Wolfram syndrome. Thank you again, Ale and the team Alejandro!

I often get questions about “regenerative medicine.” I really like the following video created by the Mayo Clinic. “Regenerate” is the opposite of “degenerate.” Because Wolfram syndrome is a degenerative disease, the best way to counteract is to “regenerate” damaged tissues.

http://www.mayo.edu/research/faculty/nelson-timothy-j-m-d-ph-d/bio-00027362

I hope you will have a wonderful Labor day today.

Dr. Freireich said, “You swear to give people hope.”

Today I would like to begin by thanking everyone who has been reading my blogs.

I checked the statistics function of my blogs yesterday and found something unexpected. Several thousand people read my blogs every week! Why? I don’t know, but I was so moved and surprised. I am so glad that many people are interested in Wolfram syndrome and Type 1 Diabetes. Thank you so much. I feel grateful.

I was reading Malcolm Gladwell’s book, David and Goliath. This book describes “Underdogs, Misfits, and the Art of Battling Giants.” I am an underdog and battling giants, Wolfram syndrome and Type 1 Diabetes. So I really enjoyed reading this book. I was struck by a story of Dr. Emil “Jay” Freireich. He was an immigrant doctor and absolutely an underdog. He said, “As a doctor, you have to figure out a way to help them, because people must have hope to live. You swear to give people hope. That’s your job.” Dr. Freireich discovered a novel treatment for acute leukemia and saved many people’s lives. He received Albert Lasker Medical Research Award in 1972.

iPS cells and Personalized Medicine

We have created many induced pluripotent stem cells (iPS cells) from skin cells of Wolfram syndrome patients.

Because these cells can be differentiated into any types of cells, including brain cells, eye cells, and insulin-producing pancreatic cells, we can use these cells to replace damaged tissues in our patients in the future.

In addition to this, there is another advantage in making iPS cells. We can use these cells now. We can test the efficacy of different candidate drugs using brain cells and eye cells differentiated from iPS cells. It seems like that patients’ cells respond to different treatments based on their genetic make-up. So these cells are useful for designing personalized medicine for the treatments of Wolfram syndrome. This would apply to any other diseases. Thank you again for donating your cells. I would like to expand this program and make iPS cells from all the patients with Wolfram syndrome in the world.

A platform for providing the best treatment for patients with ER Disease: Personalized Medicine

I think about this topic every day. I firmly believe that our future clinic for Wolfram syndrome and other ER stress disorders should provide “Personalized Medicine.” This 2 min-video explains about the personalized medicine very well.

Why? As I mentioned before, each patient is different, and should be treated differently. The key is to obtain complete family history and genetic information from each patient. Exome sequencing and genome sequencing should be integrated into our clinic to design the best treatment for each patient.

The article I read over and over

I have read many articles related to Wolfram syndrome.

The most-read article is entitled “Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome” describing the natural history of Wolfram syndrome. This article was written by Timothy Barrett, MB, BS (MD), PhD in 1995.
http://www.ncbi.nlm.nih.gov/pubmed/7490992

I read this paper over and over when I started working on Wolfram syndrome in 2002. I recommend that all the researchers in diabetes, neurodegeneration, and genetic diseases, read this article. 

Regenerative Therapy and Modern Medical Genetics

I think a lot about a new platform for endoplasmic reticulum disease and other rare diseases.

The new clinic requires new expertise in addition to conventional neurology, ophthalmology, and endocrinology. I feel that regenerative therapy and modern medical genetics based on high-throughput sequencing are the key players.

I found an interesting video describing regenerative medicine.
https://www.youtube.com/watch?v=v-Q2kghHwq4

I hope you will have the best week in your life.

Developing novel therapeutics to stop the progression of eye diseases

Some people say that it is not realistic to develop a novel therapy to stop the progression of eye manifestations in Wolfram syndrome. I don’t agree.

It is possible. If we can modulate ER stress in retinal cells, we can slow or stop the progression of optic nerve atrophy in Wolfram syndrome. I have found a biotech company in Seattle that is developing novel therapeutics for “sight-threatening” eye diseases. If they can do it, we can do it.  http://acucela.com/About-Us

A tablet for eye diseases?

The biotech I mentioned above is taking a very interesting strategy. They are trying to use a tablet (i.e., a pill) for delaying the progression of eye diseases.
https://clinicaltrials.gov/ct2/show/NCT02130531?term=acucela&rank=1

I was envisioning that I would use ophthalmic suspensions (eye drops) or intravitreal injections (injection into eyes) for stopping eye manifestations in Wolfram syndrome, but we should also think about using pills.

 

Regenerative Medicine and Regenerative Therapy

Regenerative Medicine and Regenerative Therapy are the same concepts. Regenerative Therapy focuses on the clinical application of regenerative medicine. Regenerative therapy aims at growing tissues and organs from stem cells derived from patients in the laboratory and implanting them to patients.

When we establish our ER disease clinic, we should include “regenerative therapy” into our platform in addition to endocrinology, neurology, and genetics.

We have established more than 100 stem cell lines from Wolfram patients. We are currently differentiating them into eye cells and brain cells. There are many ongoing clinical trails using stem cells. My goal is to join them as soon as possible. There are many hurdles and challenges, and we need to solve them one by one.
http://clinicaltrials.gov/ct/search?term=stem+cell&submit=Search

 

Endoplasmic Reticulum Disease Clinic 4: Personalized Medicine Again

One of my goals is to practice “Personalized Medicine” in our clinic because each patient is different.

The power of genetic medicine should be fully utilized. I believe that whole genome sequencing and exome sequencing are useful for making an accurate diagnosis. The information we get from patient’s DNA can be utilized to choose the best specialists for each patient and design a regenerative therapy or gene therapy. I will talk about this more.

I feel that something wonderful is going to happen to you today!

The Last Advice from late Dr. Alan Permutt

I talked about medicine and DNA too much in the past several days. So let’s take a break and talk about Dr. Permutt.

Dr. Alan Permutt

The late Dr. Alan Permutt

As many of you know, I took over Dr. Alan Permutt’s research program on Wolfram syndrome two years ago. I believe that it was controversial that a young foreign physician would take over Dr. Permutt’s position. As I mentioned in my previous blogs, I was leaving research when Dr. Permutt asked me to come to Washington University. So I talked with him many, many times before I made a decision. He assured me that other Washington University doctors, including Dr. Semenkovich, Dr. Fraser, Dr. Hershey, Dr. Marshall, Dr. White and others, would help me. He also told me that the Snow Foundation would support me. What he told me was all true. All the doctors have been supportive and helping me a lot, which I always appreciate. The support from the Snow foundation is enormous. I always feel that our higher power lets us work together.

The last advice from Dr. Permutt was the following.
“Fumi, All of my colleagues will help you. Just trust them. You will take us to the next level, and all of your new colleagues will help you.”

I see a big smile in your face! I hope you will have the best day in your life. I am sending kind thoughts towards you!