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A cure for Wolfram syndrome could lead to a cure for diabetes.

Sunday, August 31, 2014

Adult beta cells proliferate? How about eye cells and brain cells?

I talked about stem cell-based therapy yesterday. In parallel, we are seeking a way to increase the proliferation of remaining insulin-producing cells (i.e., pancreatic beta cells) and eye cells.

Is it possible? Growing evidence indicates that adult human beta cells can proliferate under certain conditions. The challenge is that adult human beta cells have very low proliferation rates. So we need to find a way to "increase" the proliferative potential of adult human beta cells. Interestingly, significant levels of proliferation occur during pregnancy.


We are considering leveraging our potential to increase the proliferation of our beta cells and neuronal cells. One of our candidate molecules is MANF. MANF is produced in our brain cells. The following article shows that MANF can increase the proliferation of "rodent" beta cells. Our next step is to develop a way to activate MANF and increase the proliferation of human beta cells and eye cells.
http://www.ncbi.nlm.nih.gov/pubmed/24726366

Thank you for reading this blog. I hope you will have a wonderful Sunday! I am sending kind thoughts toward you.



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.

Friday, August 29, 2014

I feel grateful because...

I receive a few hundred emails from patients with Wolfram syndrome and diabetes every week. As I mentioned in my previous blogs, I respond to every single email. It is my privilege to work for you. So please feel free to contact me.

I was grateful yesterday. I had a few meetings, and I could feel that things are going into the right direction. The unmet medical needs should be fulfilled and patients should receive the best care. On my way home, I remembered Dr. Rossini's words. He was my mentor. "Fumi, we should always offer help to our patients. Before they leave, please make sure if they still need help. Please make sure you offer help with compassion." He always emphasized the importance and power of "kindness" and "compassion".

I hope you will have a wonderful weekend. Thank you for reading this. I am here for you.

Thursday, August 28, 2014

Collaboration with Dr. Gil Leibowitz

I am very grateful today. We will officially work with Dr. Gil Leibowitz at Hadassah Medical Center in Jerusalem on Wolfram syndrome, and this will be funded by the US-Israel Binational Science Foundation in the next four years. We will develop and test a new treatment for Wolfram syndrome. 
http://www.hadassah-med.com/doctors/prof-leibowitz-lev-gil.aspx

Dr. Leibowitz is my long-term collaborator. He is a dedicated physician and scientist, and a very kind and reserved person. I first met with him at a diabetes meeting in France several years ago. I presented our work on Wolfram syndrome and Dr. Leibowitz showed his data on ER stress in beta cells. He mentioned that he had patients with Wolfram syndrome. Dr. Leibowitz has conducted a small scale clinical trial on Wolfram syndrome.
http://clinicaltrials.gov/show/NCT01302327

I feel grateful today and appreciate this opportunity. Thank you, thank you, thank you. I hope you will have a wonderful day.

Wednesday, August 27, 2014

Chasing the cure for Wolfram syndrome

I'd like to propose a two-step strategy to achieve a cure for Wolfram syndrome. The first step is to stop the progression using a small molecule (i.e., a drug) and the second step is to replace the damaged tissues using a stem cell technology. In parallel, we try to restore the functions of remaining pancreatic beta cells, eye cells, and brain cells using a small molecule or biologics such as MANF. A new technology called a "genome editing" can be combined with a "gene therapy." All of these are ongoing in my team.

I believe that these are all achievable goals. John Crowley, a father of two children with Pompe disease, and William Canfield, MD, PhD, a Pompe disease researcher, worked together, established a biotech, and discovered a treatment for the disease. Mr. Crowley could save his children's lives and is now looking for a cure. If they can do it, we can do it.

https://en.wikipedia.org/wiki/John_Crowley_(biotech_executive)
https://en.wikipedia.org/wiki/William_Canfield

Tuesday, August 26, 2014

Thank you for your support

It has been just two years since I joined the Washington University Medical Center. It was a very hot summer when I started. It was completely unexpected that I came here. I always feel that there is a higher power guiding me in my quest to find a cure for Wolfram syndrome and Type 1 Diabetes.

I hope you read Stephanie Snow Gebel's blog. I think that her power of mind attracted me from the other side of this planet.
http://thesnowfoundation.org/mom-mission/

I feel grateful today. Thank you again for reading this blog. I always appreciate your support.

Monday, August 25, 2014

Combination therapy

I often speak with people from pharmaceutical companies and R&D specialists. One of the important ideas that I have learned recently is "combination therapy."

Combination therapy is therapy that uses more than one medication. We could potentially mix two anti-ER stress drugs or mix anti-ER stress drug and anti-oxidative stress drug. There are many possibilities to improve our therapeutic strategy. 

Many people are trying to help us. Thank you so much. I feel grateful. I hope you will have a splendid Monday.

Sunday, August 24, 2014

Chasing the cure

We are chasing the cure for Wolfram syndrome and Type 1 Diabetes. I always believe that there must be a cure, and we just don't know how to do it now. I see the light at the end of the tunnel, and keep on running.

I was encouraged by the oath written by our first year medical students. Here is the first sentence.

I pledge that my patient will always be my foremost consideration.
http://whitecoat.wustl.edu/2014/

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

Saturday, August 23, 2014

1000-5000-25000 and...Thank you!

Mr. X: How many people have Wolfram syndrome? 
Me: 1000 in the US.

Mr. X: So you are working on an ultra rare disease. You are trying to help 1000 people.
Me: Yes.

Mr. X: You are helping their family too. So you are helping 5000 people. They also have families. So you are helping 25000 people. These 25000 people also have families and friends. So you are helping.....

Thank you, Mr. X. You made my day. I hope you will have a wonderful weekend. We are all connected.



Friday, August 22, 2014

Unusual forms of diabetes are not so rare

I have recently learned that unusual forms of diabetes, including Wolfram syndrome, are not so rare.  I am talking about diabetes patients whose manifestations are unusual for type 1 or type 2 diabetes. Significant advances have been made in our understanding of genetic forms diabetes, which accounts for around 1-3% of diabetes cases. These patients should be managed and treated differently. Personalized medicine may start from treating these patients.

Thank you again for reading my blog today. I am hopeful, and feel that something wonderful is going to happen to us today. Stay tuned!


Thursday, August 21, 2014

A stem cell-based replacement therapy

As I mentioned in my yesterday's blog, a stem cell-based beta cell replacement therapy has been approved by the FDA. I was so happy and grateful. This is an important step towards a cure for diabetes. The clinical trial for this new therapy will be led by Viacyte, a biotech company in California.
http://wolframsyndrome.blogspot.com/2014/08/genetic-testing-and-targeted-treatment_20.html

How do they do it? Here is their strategy.
1. Make insulin-producing cells from human embryonic stem cells.
2. Put these insulin-producing cells in a special capsule (device).
3. Implant the capsule under the skin.

What does this mean? If this technology keeps on improving, patients with diabetes don't need insulin injections. I was very happy and felt grateful to the company and investigators who developed this novel therapy.

What should my team do? We should keep on producing induced pluripotent stem cells (iPS cells) from skin cells of patients and create retinal cells from these iPS cells to implant them to patients. We should follow Viacyte's success. 

Thank you for reading this blog. Our friend and colleague, Stephanie Snow Gebel told me the importance of HOPE yesterday. I am HOPEFUL today. I HOPE you will have a wonderful day.

Wednesday, August 20, 2014

Genetic testing and Targeted Treatment Q&A and Good News

I received a lot of questions regarding my yesterday's blog.
http://wolframsyndrome.blogspot.com/2014/08/genetic-testing-and-targeted-treatment.html

Most people asked me, "Is it really beneficial for patients? Is genetic testing really helpful?" Yes, it is. We have a very good example. Our friend, Dr. Bess Marshall, discovered that some patients with juvenile diabetes should be treated with a drug called sulfonylurea instead of insulin more than 10 years ago. This was based on genetic testing of one gene. As of today, our hospital has a capability of performing genetic testing of more than 3000 genes at once. This is called "Exome Sequencing."

By the way, I had wonderful news yesterday. A stem cell-based beta cell replacement therapy has been realized. I was so happy yesterday. I will discuss this more tomorrow. 
http://viacyte.com/press-releases/viacyte-inc-announces-fda-acceptance-of-ind-to-commence-clinical-trial-of-vc-01-candidate-cell-replacement-therapy-for-type-1-diabetes/

Tuesday, August 19, 2014

Genetic testing and Targeted Treatment

There is growing interest in the clinical applications of new DNA sequencing technology. In short, physicians start using the information of all the genes from a patient to make diagnosis and identify the best treatment. This is called "targeted treatment." This is useful for determining necessary tests and suitable treatments. I will talk more about this. I am also looking into gene therapy now because of several reasons, and plan to introduce this to you. 

Thank you for reading this. Something wonderful is going to happen to us today! 

Monday, August 18, 2014

How to make beta cells

I keep on thinking how to stop the progression of Wolfram syndrome. If we can accomplish this, what is our next step? Our next step is to replace damaged tissues. The rapid progress in the field of regenerative medicine will make this possible. The beta cell replacement therapy using stem cells is becoming a reality.
http://jdrf.org/press-releases/jdrf-to-support-viacyte-s-development-of-innovative-encapsulated-beta-cell-replacement-therapy-for-diabetes/

This article articulates the current strategies for making insulin-producing cells. There are two ways. 1. Make beta cells from stem cells. 2. Stimulate the proliferation of remaining beta cells. This is exactly what we are trying to do for eye cells.
http://www.ncbi.nlm.nih.gov/pubmed/19781928

I hope you will have a wonderful Monday. I am sending kind thoughts towards you. Thank you for reading this.



Sunday, August 17, 2014

Changing the Mindset to Develop Therapeutics

I feel that I need to change my mindset to develop diagnostics and therapeutics for Wolfram syndrome and Type 1 Diabetes. We learn how to diagnose and treat patients using established drugs and devices in medical schools. In academic medicine, we tend to think about publishing our findings. To bring new drugs, diagnostic methods, and devices to patients, we should have different mindset and expertise. I am learning and changing. The pipeline is a "serendipity", and then we need to get out from research to achieve a clinical implementation of the discovery.

I was reading the oath written by our first-year medical students for their White Coat ceremony on August 15. It says, "I pledge that my patient will always be my foremost consideration." It is always good to remember the spirit that you started with.

I am sending kind thoughts towards you. I hope you will have a wonderful day. Thank you for reading this.

Saturday, August 16, 2014

Thank you my friends. I hope you read this.

We need to develop therapeutics for Wolfram syndrome as soon as possible. We need to stop the progression now, and replace damaged tissues in the future. I always appreciate the feedback from officers and researchers in biotech and pharmaceutical industries to bring our candidate drugs to patients faster. I am doing my best. Thank you again for reading my blog today.
http://thesnowfoundation.org/keeps-going-hope/

Friday, August 15, 2014

Thank you, Thank you, Thank you again

I am grateful that many people support our therapeutic development for Wolfram syndrome. I am so grateful for supports from our patients, their families, our colleagues at Washington University, Dr. Barrett and his team, Dr. Leibowitz and his team, collaborators at Amarantus and other pharmaceutical industries, and advisors for R&D and the pre-clinical and clinical trial processes. I always believe that a cure for Wolfram leads to a cure for diabetes and blindess. 

Our diagnostic and therapeutic development for Wolfram syndrome and Type 1 Diabetes is supported by National Institutes of Health, Juvenile Diabetes Research Foundation, American Diabetes Association, Amarantus, the Team Alejandro, the Team Ian, the Ellie White Foundation for Rare Genetic Disorders, and the Jack and J.T. Snow Scientific Research Foundation. There are a few other companies that give us advice.

Thank you, Thank you, Thank you again.


Thursday, August 14, 2014

My friends, I hope you read this

I was reading a blog written by Stephanie Snow Gebel who has a daughter with Wolfram syndrome. I was so moved. Stephanie created a non-profit organization to raise awareness and achieve a cure for Wolfram, and we have been working together since I moved to Washington University. I hope you read this. We need to develop novel therapeutics for Wolfram syndrome as soon as possible.
http://thesnowfoundation.org/day-life-wolfram-syndrome-mom/

Wednesday, August 13, 2014

Thank you and Good News

Two great things happened to me yesterday, and I would like to share these with you.

Our friends, Dr. Bess Marshall and Dr. Neil White, have been placed on the Best Pediatricians List in America for 2014! They are my wonderful colleagues and working on Wolfram syndrome together with me. I felt so happy yesterday. I always feel honored to work with wonderful colleagues at Washington University and other institutions in the world to find a cure for Wolfram syndrome.

My former trainee who is currently a staff scientist at UCSF and I gave lectures in the same session at a scientific meeting. I gave a lecture on Wolfram syndrome, and my former trainee, Rajarshi Ghosh, described a new small molecule that can be used for the treatment of ER stress-related diseases, including diabetes and retinitis pigmentosa. I was very proud of Rajarshi and his accomplishments. I was so happy.

I felt grateful yesterday, and still feel grateful today. I feel that something wonderful is going to happen. I hope you will have a wonderful day.

Tuesday, August 12, 2014

Thank you, Thank you, Thank you

I receive 20-30 emails related to Wolfram syndrome and Type 1 Diabetes every day. Most of them are from patients, their families, and doctors. I respond to every email. Sometimes my email is short, and I try to respond to every email. 

I appreciate that they share their experiences, concerns, symptoms, and other things with me. Thank you so much. I am doing my best to develop novel therapeutics for Wolfram, and I am encouraged by these emails. Thank you again. I hope you will have a wonderful day. Take care.

Monday, August 11, 2014

The need for clinical implementation

I strongly feel that we need to move out from research to advance to a next step, interventional studies. We have candidate small molecules and a peptide to develop novel therapeutics for Wolfram syndrome and Type 1 Diabetes. I feel the need for clinical implementation of all of our previous discoveries. We need to get out from research and use our discoveries in a clinical environment. I am working on it.

Sunday, August 10, 2014

Dose escalation study?

Recently, I often speak with medical and scientific officers of pharmaceutical industries. On Thursday, I had an exciting discussion with several officers of a pharmaceutical company. On Friday, I had another fruitful discussion with an expert in R&D, and Regulatory & Clinical Trials. I have a much better idea of what I should do to perform interventional studies for Wolfram syndrome and Type 1 Diabetes. 

What is most important? The answer is a "small molecule." We need a small molecule (i.e., a drug) to perform a clinical trial. This is probably obvious to anyone. We need another important component, the dose. We need to establish the recommended dose. There are multiple ways to accomplish this, and I am learning these.

I hope you will have the best Sunday in your life!

Saturday, August 9, 2014

A Small Molecule for Wolfram?

We are looking for small molecules for developing novel therapeutics for Wolfram syndrome. What is a small molecule?

A small molecule is a low molecular weight chemical compound that may help regulate a biological process. So a small molecule almost means a drug. Some drugs are not small molecules. We have several small molecules that can potentially delay the progression of Wolfram syndrome. Three of them are FDA-approved small molecules, and one of them is a FDA-approved peptide.

I hope you will have a wonderful weekend!

Friday, August 8, 2014

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.

Thursday, August 7, 2014

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.

Wednesday, August 6, 2014

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.

Tuesday, August 5, 2014

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. 

Monday, August 4, 2014

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.

Sunday, August 3, 2014

A tablet for eye diseases?

The biotech I mentioned yesterday 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.

Saturday, August 2, 2014

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

Friday, August 1, 2014

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