We are looking for disease modifying loci for Wolfram syndrome to identify new drug targets. What are disease modifying loci? These are the genes that may play a role in delaying or accelerating the progression of the disease. In addition to WFS1 or WFS2, it seems like there are genes affecting the manifestations of the disease. If we can identify these genes, we may be able to target the products of these genes to delay the progression. So we are searching for these genes.
Thank you for reading this blog. I hope you will have a wonderful week. I am sending kind thoughts toward you. Warmly, Fumi Urano
I received several questions related to my blog of September 26, 2014.
http://wolframsyndrome.blogspot.com/2014/09/soluble-factors.html
How can we utilize MANF, a natural soluble factor produced in our body, to protect and proliferate remaining beta cells and neurons?
The key is to understand how MANF simulates the proliferation and enhances the function of remaining tissues. It seems like there are two independent mechanisms. There are two different mediators for MANF in our body. Thus, our goal is to develop two different types of small molecules to enhance the functions of endogenous MANF. Another option is to inject recombinant MANF. Because of several scientific reasons, we prefer small molecules at the moment.
Thank you for reading this blog. I hope you will have a wonderful and beautiful Sunday. Please feel free to contact me if you have any questions. I am here for you. Take care, Fumi Urano
I keep on figuring out how to delay the progression and provide a cure for patients with Wolfram syndrome. In parallel, I keep on thinking about how we can improve the quality of life of our patients. One of the possibilities is to create a planform where patients can share their experiences. There are multiple non-profit and for-profit organizations working on this. Patients-like-me is one of them.
http://www.patientslikeme.com/
I am willing to donate our data from our patients to this type of organization. Of course, the data should be de-identified. If it is difficult to do it because of all the regulations, I am willing to help people create such a platform. By connecting each other, we would feel empowered, I think.
Thank you for reading this blog. I hope you will have a wonderful weekend. Kindly, Fumi Urano
We are looking for soluble factors in our body that can enhance the regeneration of damaged tissues in Wolfram syndrome and Type 1 diabetes. We have discovered two molecules so far. One of them is MANF.
We are trying to produce a large amount of these factors in the dish (recombinant proteins) and give these factors to animal models and cell models. We are also looking for methods/small molecules (i.e., drugs) to enhance the functions of these factors. This strategy is also related to "regenerative therapy", but independent of stem cells.
Thank you for reading this. I hope you will have a wonderful Friday. Warmly, Fumi Urano
Currently we are focusing on manipulating cellular calcium (ER calcium) homeostasis using small molecules (i.e., drugs) to delay the progression of Wolfram syndrome. In addition, I want to take another strategy, which is to alleviate cell stress using chemical chaperones. Chemical chaperones are small molecules that can reduce ER stress by stabilizing defective cellular proteins. It is a "crutch" for defective Wolfram proteins in patients with Wolfram syndrome. We may want to combine this strategy with our current strategy.
I hope you will have a wonderful day. Take care, Fumi Urano
In Wolfram syndrome, some cells are sensitive to the loss of function of Wolfram gene. These are insulin-producing pancreatic beta cells, some brain cells, and some eye cells. Why are these cells are sensitive? This is the key to provide a cure for Wolfram syndrome. If we know why these cells are sensitive, we can design a therapy for protecting these cells. In the past 24 months, we discovered that loss of function of Wolfram gene causes dysregulated calcium homeostasis in our cells. So we are trying to manipulate calcium homeostasis by drugs to delay the progression. We still don't know why these cells are sensitive to dysregulated calcium homeostasis. I keep on thinking.
Thank you for reading this blog. I hope that I will receive the key soon. Warmly, Fumi Urano
Dr. Roger Perlmutter joined Merck just 18 months ago and has significantly improved the company’s record of getting drugs through the FDA. Why? I think we should learn from his success. He focuses on the most important thing that they can do and that will have the biggest benefit for patients. "The Biggest Benefit for Patients." I will keep on focusing on the biggest benefit for patients.
https://en.wikipedia.org/wiki/Roger_M._Perlmutter
Thank you for reading this. I hope you will have a wonderful day. Warmly, Fumi Urano
I have been testing the possibility that existing drugs for other disorders may be beneficial for Wolfram syndrome patients. This is called "drug repurposing." This is not an crazy idea. For example, avastin which is licensed to treat various cancers is beneficial for patients with age-related macular degeneration (AMD) and diabetic retinopathy. Until we develop a drug specifically designed for Wolfram syndrome, I will keep on testing existing drugs.
Thank you for reading this blog. I am sending kind thoughts toward you. Take care, Fumi
The charity road trip 2014 in aid of Wolfram syndrome UK was successful! They have delivered the last of the information packs to the Hospital of Sick children Edinburgh.
https://www.facebook.com/NSHBWS
https://www.facebook.com/pages/Wolfram-Syndrome-UK-DIDMOAD/174039922735501
Thank you again, Jennifer, Tracy and Paul Lynch, Alan Nye, and their team. I could feel your PASSION and HOPE. I am very proud of you and your team. I look forward to meeting with you soon.
I feel grateful today. Thank you again for reading this blog. I hope you will have a wonderful Sunday. Take care, Fumi
I am trying to bring our new therapies to patients. As you can imagine, there are multiple steps to achieve it. Our medical center has the Institute for Clinical and Translational Sciences and they have been helping us make this happen. Our institute is supported by NIH. The institute is led by Dr. Bradley Evanoff and Dr. Kelle Moley. They have been supportive and offering us wonderful opportunities. I always appreciate their continuous support and encouragement.
Thank you again for reading this. I hope you will have a wonderful day.
A new article on a stem cell-based therapy for diabetes has been just published. With this method, we can make insulin-producing cells in 15 days. This is incredible.
http://www.ncbi.nlm.nih.gov/pubmed/25211370
In Type 1 Diabetes, we still need to find a way to avoid autoimmunity. In Wolfram syndrome, we need to modify the WFS1 gene locus in skin cell-derived stem cells. However, I feel that a cure for diabetes is approaching. We should keep on developing new therapy to provide a cure for patients suffering from challenging conditions. I would like to thank Dr. Kieffer's team and Dr. Johnson's team for developing this new method.
Thank you again for reading this blog. Thank you for your continuous support and encouragement. Thank you, Thank you, Thank you. Take care, Fumi
I had a productive conversation with an executive director of Missouri Cures, a non-profit organization promoting stem cell research in Missouri. I had a chance to explain our strategy to provide a cure for Wolfram using induced pluripotent stem cells derived from skin cells of patients. They will help us raise awareness of Wolfram and develop novel therapeutics using iPS cells. Please stay tuned.
http://missouricures.net/
I feel so grateful that many people are now helping us develop therapeutics for Wolfram syndrome. Thank you, Thank you, Thank you. I hope you will have a wonderful day today.
I always appreciate the efforts of patient support groups. I have been communicating with the Wolfram Syndrome UK in England
http://www.wolframsyndrome.co.uk/#
They will have an important event this weekend. They will deliver much needed information about Wolfram syndrome to medical professionals in 25 major children's hospitals over the weekend in less than 60 hours! Tracy and Paul Lynch are busy preparing for the event.
http://www.charityroadtrip.co.uk/2014-roadtrip-challenge
Thank you again for your sincere efforts, Tracy, Paul, and Alan Nye. Thank you, Thank you, Thank you. I hope you will have a wonderful week.
A revolutionary surgery was performed last week by Dr. Masayo Takahashi's group in Kobe, Japan. Dr. Takahashi's team created retinal cells using skin cells of a patient with macular degeneration and transplanted them back to the patient.
http://the-japan-news.com/news/article/0001564776
Here is a summary of their new therapy to restore vision
1. Collect skin cells from a patient.
2. Create induced pluripotent stem cells (iPS cells) from skin cells of the patient.
3. Differentiate iPS cells into retinal cells.
4. Transplant these retinal cells back to the patient.
We still don't know if this patient's vision will improve. However, this is an important step toward a cure for blindness. Our team is taking a similar strategy, and I hope that we can create multiple types of retinal cells and transplant them back to our patients.
I was very encouraged by the news. I am hopeful. Thank you for reading this blog. I hope you will have a wonderful Sunday.
Patient support groups have been helping us a lot. The Worldwide Society of Wolfram syndrome was established by Mr. Robert Birkinshaw. It was taken over by Mr. Kip Branch and Mrs. Pat Gibilisco is currently running the program. The Jack and JT Snow Foundation and The Ellie White Foundation have been helping our team's research toward a cure for Wolfram syndrome. I always appreciate their sincere efforts.
http://www.didmoad.org/
I hope you will share the following video created by the Jack and JT Snow Foundation. I hope you will help us spread the word. http://vimeo.com/82103685
Thank you again. I feel grateful. I will talk about a new therapy for providing a cure for blindness later today. http://the-japan-news.com/news/article/0001564776
I hope you will have a wonderful weekend. Take care, Fumi
I am always interested in a new therapy, especially non-invasive ones. My good friend at the medical center, Dr. Phil Cuculich, developed a new therapy for atrial fibrillation, a common heart disease, that can potentially cause a stroke. His new therapy and a patient he saved were reported in the Fox News recently. The patient was brave and shared his story with the public. I would like to thank both Dr. Cuculich and his patient.
Many of our Wolfram syndrome patients are brave like Phil's patient. They share their experiences in the public, which raises awareness of the disease. I cannot thank you enough. Thank you, Thank you, Thank you. I keep on moving forward to bring a new therapy to them like Dr. Cuculich.
http://thesnowfoundation.org/about-us/the-heroes-of-wolfram-syndrome/
In the past two years, my team has identified drug targets, developed animal and cell models of Wolfram, and identified small molecules for treating patients with Wolfram syndrome. We completed key preclinical studies last week and submitted a research article to the National Academy of Sciences of the USA (Medical Science section) last night. I have been fortunate to have wonderful fellow scientists, physicians and technical assistants in my team. I felt so grateful. Based on these findings, we keep on moving forward to advance to our next step.
Here is the acknowledgment section of our article.
We thank all of the participants in the Washington University Wolfram Registry and Research Clinic and their families for their time and effort (https://wolframsyndrome.dom.wustl.edu/). We also thank Mai Kanekura, Mariko Hara, and Karen Sargent for technical support and the Washington University Wolfram Study Group Members and the study staff for advice and support in the greater research program. This work was supported by grants from NIH (DK067493, P60 DK020579, and UL1 TR000448), JDRF (47-2012-760 and 17-2013-512), ADA (1-12-CT-61), the Team Alejandro, the Team Ian, the Ellie White Foundation for Rare Genetic Disorders, and the Jack and J.T. Snow Scientific Research Foundation to F. Urano. We dedicate this article to late Dr. M. Alan Permutt, and Mr. Jonathon Wasson who devoted their lives to Wolfram syndrome research. Their deaths were a great loss for us all.
Thank you for reading this blog. I saw many videos of people participating in the bucket challenge for Wolfram syndrome. I appreciate your support. Thank you, Thank you, Thank you.
I feel that this week is going to be a great one. Many good things happened yesterday.
Lasker Medical Research Award Winners were announced yesterday, and two of the recipients were ER stress researchers! This was great news in the field of ER stress! I sent them emails right away, and they responded to me right away! Thank you!
My former student texted me and let me know that her first class (as a professor) went well. I felt great!
We could confirm that our potential drugs for Wolfram can restore both beta cell and neuronal cell functions. The dose escalation study using beta cells is ongoing. I was encouraged.
Thank you for reading this. I feel grateful. I hope you will have a wonderful day.
I am optimistic because I see possibilities. We have FDA-approved drugs, new drugs, stem-cell therapies, and genome-editing therapies. When I came to Washington University Medical Center two years ago, none of these existed. So I have reasons to be optimistic.
Thank you for reading this blog. I hope you will have a wonderful week. I am grateful, optimistic, and hopeful. Thank you again.
In Wolfram syndrome, insulin-producing beta cells in the pancreas and brain cells selectively degenerate. Why? We extensively studied their skin cells and lymphocytes, and did not find any problems although these cells have impaired WFS1 functions. I always think that this mysterious finding will eventually lead to a cure for Wolfram. If we understand why beta cells and brain cells are sensitive to impaired Wolfram gene functions, we can design a new treatment.
We got encouraging results last week. It seems like that the same drug can potentially restore functions in beta cells and brain cells of Wolfram patients. Our results suggest that pancreatic beta cells and brain cells degenerate by the same mechanisms. Thus, a drug that can stop the degeneration of beta cells should be able to stop the degeneration of brain cells and eye cells. I was really encouraged. We should keep on moving forward.
I hope you will have a wonderful Sunday. I am sending kind thoughts toward you.
My interview will be published in "Resident Note" soon. This is a Japanese journal for young physicians. I talked about my career path and explained why I started working on Wolfram syndrome. I was reading a draft prepared by editors of the journal and realized that it was not an accident that I came to Washington University. All the patients whom I met in the past brought me here. It is a little difficult for me to explain by words, but I realized that I was brought here from the other side of this planet with a reason. So I will keep on doing my best.
I hope you will have a wonderful weekend. Thank you for reading this. I always appreciate your encouragement, support, and kind words. Thank you again. I am doing my best and will keep on doing my best.
I think about two S's all the time, Small molecules (i.e., drugs) and Stem cell-based therapy.
In Wolfram syndrome, there is imbalance of calcium levels between two cellular compartments. It seems like that brain cells and insulin-producing beta cells are sensitive to misregulated calcium homeostasis. Using small molecules, I would like to tip the balance to our favor. We are getting encouraging results.
By the way, I was speaking with Dr. Louis Philipson, Director of the Kovler Diabetes Center at the University of Chicago. He shared with me wonderful ideas on potential treatments for Wolfram syndrome. Dr. Philipson always has intelligent and constructive ideas. The following video is quite encouraging. We will follow Dr. Philipson's success.
http://kovlerdiabetescenter.org/videos/
http://kovlerdiabetescenter.org/bios/louis-h-philipson-md-phd/
I think about what I can do for patients with Wolfram syndrome every day. A cure for Wolfram can lead to a cure for diabetes, I believe.
http://wolframsyndrome.blogspot.com/2014/09/if-we-had.html
I am visualizing the world with:
1. Compassionate physicians who know how to manage the conditions.
2. Drugs that can stop the progression.
3. Therapies replacing the damaged tissues.
Thank you for your continuous support and encouragement. Thank you, Thank you, Thank you.
Base on emails and phone calls from patients and their families, I am focusing my energy on the following three things. If we had these three, what would happen to us? Am I in the right direction?
1. Compassionate physicians who know how to manage the conditions.
2. Drugs that can stop the progression.
3. Therapies replacing the damaged tissues.
Thank you again for reading this. I am sending kind thoughts toward you.
I thought a lot about how to create HOPE for patients suffering from Wolfram and other rare conditions during the Labor day weekend. If I were a patient, what would I want? These are the three things that I came up with.
1. Compassionate physicians who know how to manage the conditions.
2. Drugs that can stop the progression.
3. Therapies replacing the damaged tissues.
I think we have #1. Our friend, Dr. Bess Marshall, and her colleagues at the St. Louis Children's Hospital know a lot about Wolfram now. Our friend, Dr. Tammy Hershey, organized a research clinic, which helped these physicians learn about Wolfram syndrome. We need more physicians in different states and countries.
How about #2 and #3? I feel that #2 is getting closer. #3 requires the development of regenerative medicine center. I am working on both.
Thank you for reading this. I hope you will have a wonderful day.
I was watching the video that our friend and patient, Alejandro, was doing an ice bucket challenge. 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."
https://www.youtube.com/watch?v=Dbnn4GqrgPc
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.
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.
https://www.youtube.com/watch?v=qRCxvNXGx9g
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.
