John T. Milliken Department of Internal Medicine
Upcoming clinical trials We need new treatments and therapeutic modalities for Wolfram syndrome, including oral and injectable medications for optic nerve atrophy and neurological issues. I have been focusing my efforts on developing a new drug, AMX0035, to treat Wolfram syndrome in collaboration with Amylyx Pharmaceuticals in Cambridge, Massachusetts, USA. AMX0035 targets endoplasmic reticulum stress […]
I gave a talk for the Wolfram UK conference virtually last week. I updated the audience about our therapeutic development for Wolfram syndrome. The talk is now available via youtube. https://www.youtube.com/watch?v=pUyLPpwOM8Y Fumi URANO, MD, PhD
I have some exciting updates on our gene therapy development. The root cause of Wolfram syndrome is pathogenic changes in the WFS1 gene. Therefore, correcting these changes in the WFS1 gene is the best way to treat Wolfram syndrome. We initially used the original CRISPR-Cas9 gene editing technology and then used a newer technology, base […]
February 28th is Rare Disease Day, and Every day is Rare Disease Day, Wolfram syndrome day, for me. I keep on doing my best to provide the best clinical care, raise awareness, and develop safe and effective treatments for patients with Wolfram syndrome. Let’s work as one team and make a difference together. Fumi Urano
February 3rd was National Women Physicians Day! Hats off to all the women physicians, including my mom, a compassionate pediatrician/internist who sent my brother, and me to medical school after my dad passed away. She is our hero, best doctor, and best mom in the world. She encouraged me to keep on working on Wolfram […]
My strategy is to stop/delay the progression of Wolfram syndrome using oral medications and restore functions of retinal ganglion cells, brain cells, and insulin-producing cells by regenerative gene therapy. Our first target is vision. We have been trying to improve visual acuity using viral vectors expressing a healthy Wolfram gene (WFS1) and a regenerative factor called […]
Wolfram syndrome is often misdiagnosed as Type 1 diabetes. Patients with early-onset diabetes mellitus who are negative for islet autoantibodies and lean may have syndromic monogenic diabetes. Monogenic diabetes genetic testing, including WFS1 gene, should be considered for such patients (https://www.sciencedirect.com/science/article/pii/S2376060522000013?via%3Dihub).
As you know, we all have two copies of the Wolfram syndrome 1 (WFS1) gene, one from our mother and one from our father. Patients with Wolfram syndrome have two mutated copies of the WFS1 gene, and their parents have one mutated copy and one normal copy. They are carriers. Dr. Hattersley and I identified […]
We recently identified a WFS1 gene variant associated with a mild form of Wolfram syndrome in the Ashkenazi Jewish population. This WFS1 gene variant, WFS1 c.1672C>T (p.Arg558Cys) is prevalent in the Jewish population, and 1/30 Jewish people are carriers. We have deposited the data to the public database (https://www.biorxiv.org/content/10.1101/2021.11.07.467657v1). I have been extensively studying this […]
In the past, I looked for existing drugs that could be beneficial for patients with Wolfram syndrome. This effort led to a few clinical trials, but a repurposed drug could be just a band-aid for Wolfram, and we need a new medication for Wolfram syndrome. I have been focusing my efforts on developing a new […]
I saw an adult patient with Wolfram syndrome in my WFS1 clinic a few weeks ago as usual. She flew in just like other patients, but she was a little different from others. Although she had low vision, she came to my clinic with a white cane by herself. Most of my patients with low […]
I saw multiple patients with Wolfram syndrome from different states in the past few weeks. They flew in to see me in my WFS1 clinic during the Omicron surge. I felt so privileged and honored to see them as a doctor. I often see patients with Wolfram and WFS1-related disorders who even come from abroad. […]
December 3, 2021 Dear All, I hope you and your family are doing well. We live in a time of tumult. Many are wary of all the negativity, but I am incredibly positive and energetic and committed to making a difference. Our lab is 100% functional, and we are making steady progress. Here is a […]
May 30, 2021 Dear All, Hello everyone. I pray you’re in great spirits. Everyone in my research team has been vaccinated for COVID-19, and we are working very hard to develop novel treatments for Wolfram syndrome. Although our past has been harsh, our future looks brilliant now. I continue adhering to my three guiding principles: […]
As many of you are aware, Science Magazine featured my basic, translational, and clinical research on Wolfram syndrome. The article covers the history of Wolfram syndrome and its research. https://www.sciencemag.org/news/2021/02/race-treat-rare-fatal-syndrome-may-help-others-common-disorders-diabetes https://science.sciencemag.org/content/371/6530/663 This is a rare and amazing opportunity for us to raise awareness of Wolfram syndrome. Science initially interviewed me on endoplasmic reticulum stress (ER […]
February 6, 2021 Dear Friends, I wish and pray that 2021 is a year of splendid health and big success for you. Despite all the uncertainty, troubles, and challenges on our planet, I have focused my mind and efforts on helping and saving our patients with Wolfram syndrome and WFS1-related disorders. I have been adhering […]
Dear Friends, First of all, I want to express my gratitude for everything you’ve helped me achieve here. Your kind words and encouragement keep me motivated and inspired. My three guiding principles are: Improve clinical care, Raise awareness, and Provide a cutting-edge treatment for Wolfram syndrome. Here is our progress: A Drug-Repurposing Clinical Trial Our […]
Dear Friends, Thank you for visiting our Wolfram Syndrome website. I hope you and your family are safe, strong, and healthy on a brighter future. I have no doubt better days are ahead, and we can rise about this crisis. Many of you have asked me if I need to assist with COVID-19 research or […]
Dear Friends, Today, I would like to show my gratitude to you. I have received hundreds of emails in the past few days regarding our recent advances in regenerative gene therapy for Wolfram Syndrome that could lead to breakthrough therapy not only for Wolfram Syndrome but also for retinal degeneration, diabetes, and neurodegenerative disorders. All […]
Dear Friends, I hope you and your family are safe and well during this COVID-19 pandemic. Three things are always on my mind: Improve clinical care, Raise awareness, and Provide a cutting-edge treatment for Wolfram syndrome. As I mentioned on January 1st, I am determined to make 2020 the game-changing year for us despite this […]
Dear Friends, Happy Rare Disease Day. Thank you for your emails and messages in the past few days. I appreciate you shared your feelings with me and encouraged me regarding our therapeutic development for Wolfram syndrome. As I mentioned in my blog on January 1, 2020, I am determined to make 2020 the game-changing year […]
We have been developing drug-based therapies to delay/stop the progression of Wolfram Syndrome, and we have made significant progress. In parallel, we need to develop regenerative therapies to treat/replace damaged tissues. We have two pipelines for the regenerative therapies. 1. Stem cell-based therapies.This requires collaboration with surgeons and bioengineers. We are working on this.2. Regeneration […]
Dear Friends, Happy New Year. Thank you for your email, letters, and messages in the past few weeks. I appreciated your encouragement. I am determined to make 2020 the game-changing year for us. Three things are always on my mind: Improve clinical care, Raise awareness, and Provide a cutting-edge treatment for Wolfram syndrome. I have […]
Dear Friends, As the year 2019 is coming to an end, I would like to summarize our progress this year. Tomorrow, I would like to tell you my plan for 2020. We have been focusing our efforts on the development of regenerative and gene therapy. We successfully created the adeno-associated virus (AAV) that can deliver […]
Thank you for your continued support and encouragement. I would like to update you about our progress on the therapeutic development for Wolfram syndrome. Our clinical trial of dantrolene sodium for adult and pediatric patients with Wolfram syndrome has been going well. Based on the results of dantrolene trial, I feel confident that counteracting ER […]
I attended the Wolfram Syndrome UK annual conference on September 28, 2019. I started attending this important conference in 2014. Now I know many patients and families in the UK. This conference is special for me because I have a chance to discuss challenges patients and families have face to face. This year was also […]
Dear Friends, This year’s Wolfram research clinic was successful again. The community conference hosted by the Snow Foundation was a big success too. I would like to thank all the participants, families, and staff for the research clinic and community conference. Please feel free to contact me if you have any questions regarding the genetic […]
I have received many emails and phone calls regarding our therapeutic development for Wolfram syndrome in the past several weeks. Thank you so much for your kind words and encouragement. I would like to update you about our ongoing efforts on therapeutic development. I hope this blog will answerer some of your questions. A Drug-Repurposing […]
Thank you so much for visiting our website for Wolfram syndrome patients, their families, friends, and supporters. I hope you and your family are enjoying the beautiful autumn season and nature. I love to do a nature walk especially in autumn, and I came up with the following idea during my nature walk. I’d like […]
Dear Friends, Thank you so much for your support. I hope you are enjoying this beautiful autumn season with your family, and it is time for me to update you about our progress. Today, I’d like to talk about one of the new drugs we are developing as we have made significant progress on this […]
I’d like to begin by thanking all of you for your continued support, trust, and faith in me. I always feel your support and energy. It is always my pleasure to update you about our progress. To achieve a cure for Wolfram syndrome, we need breakthrough treatments. We currently have three new candidate drugs that […]
It is nice to see you again. I always appreciate your support, trust, and faith in me. I see patients with Wolfram syndrome every week and receive phone calls and emails from patients and their families every single day. It is definitely urgent to slow the progression of the disease and develop novel treatments for […]
Dear Friends, Nice to see you again. Thank you so much for following my mission & vision and being the kindest person. I think about patients with Wolfram syndrome and their families and friends every morning. That’s one of the first things I do every day at 4:30 am. I would like to know their […]
Dear Friends, It is always nice to talk to you. Thank you so much for reading this. I firmly believe that Wolfram syndrome is an underdiagnosed disease. Wolfram syndrome is characterized by juvenile-onset diabetes, optic nerve atrophy, diabetes insipidus, deafness, neurogenic bladder, and symptoms related to brain cell dysfunction. However, I have discovered that Wolfram […]
Dear Friends, Thank you so much for “coming to see me” today. It is always my pleasure and privilege to see you and talk to you. I feel your support and encouragement, and I am grateful for everything you have done for me, patients, patient organizations, the Snow Foundation, the Ellie White Foundation, Unravel Wolfram […]
I have three goals always on my mind: Raise Awareness, Improve Clinical Care, and Provide Novel Treatments for patients with Wolfram syndrome. As the Rare Disease Day is approaching, I would like to invite you to think about more about rare diseases, including Wolfram syndrome. There are 7,000 rare diseases and disorders that when combined […]
I would like to begin by thanking all of you for your continued support and encouragement. I appreciate it immensely. I am so grateful to have such supportive colleagues all over the world. Our drug-repurposing clinical trial of dantrolene sodium is ongoing. The trial began in January 2017. Twenty-two patients with Wolfram syndrome enrolled. Two […]
I thought a lot about our therapeutic development for Wolfram syndrome in the past several weeks. I feel that drug-repurposing may not be good enough. I firmly believe that we need a breakthrough therapy for Wolfram syndrome. This year, I would like to spend more time for developing regenerative gene therapy, especially for visual impairment. […]
Thank you for reading my blog. I always feel your support. I appreciate it immensely. As I am ready to say goodbye to 2017, I would like to update you about our progress. Our drug-repurposing clinical trial of dantrolene sodium is ongoing. The trial began in January, and nineteen patients with Wolfram syndrome from the […]
US Senator Roy Blunt (Missouri) and Director of National Center for Advancing Translational Sciences/NIH Dr. Christopher Austin visited us from Washington DC on August 9th. I had a chance to present our Wolfram syndrome clinical and research program to their teams. My colleague in Internal Medicine, Dr. Dan Ory, and I tried to tell them […]
Another successful Wolfram research clinic was completed this week. I would like to thank all the participants, Dr. Hershey, Dr. Marshall, Mrs. Samantha Ranck, and other physicians and scientists who were involved in the clinic. See you next year! Thank you again. Warmest regards,Fumi Urano
I have received many questions regarding our ongoing clinical trials, as well as questions related to our next step lately. We started the patient registry, and then moved onto the research clinic. Now, we are conducting trials. I think we are making progress, and need to speed up as we are racing against time. Although we don’t […]
I have received many emails and phone calls regarding the ongoing clinical trials for Wolfram syndrome in the US, UK, and Europe. After the discussion with Dr. Barrett’s team in the UK and other regulatory experts, we decided to summarize the gist of the ongoing clinical trials. You can find the information on the following […]
Dear Friends, I would like to update you about the status of our clinical trial of dantrolene sodium in patients with Wolfram syndrome. Dantrolene is a US Food and Drug Administration (FDA)-approved drug currently used for different medical conditions. Based on our data, we received orphan drug designation of dantrolene sodium for the treatment of […]
Our current focus is to bring our potential drugs to our patients. We are interested in drugs that can help patients “regain homeostasis.” In other words, we try to help our patients’ organ systems to keep cellular endoplasmic reticulum states stable. The challenge is that there are not many drugs that can modulate endoplasmic reticulum […]
We have become one of the first 8 members of the NIH’s Rare Disease Data Repository Program. This is one of the important projects at the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) in the USA. I have also become a steering committee member of this program. The purpose of this […]
I tried to make progress in the following three areas in 2016: 1) Improve Clinical Care, 2) Raise Awareness, and 3) Develop Novel Treatments for Wolfram syndrome. I did my best. I know I could not make a breakthrough, but I will keep on trying. My highest priority right now is to work out the […]
I attended the Wolfram UK and WellChild conference in England on Saturday, October 8th, 2016. This was my third time at the conference and met with around 100 patients and their family members. At the conference, Dr. Timothy Barrett (University of Birmingham) announced that his phase 2 randomized clinical trial of his repurposed drug in patients […]
I would like to accomplish the following three goals: #1 Improve Clinical Care, #2 Raise Awareness, and #3 Provide a Cure for Wolfram syndrome. I feel that we have been making steady progress in #1 and #2. #3 is the most challenging one. To achieve #3, we need to first delay the progression of the […]
I had a chance to present my data and concept on regenerative medicine for the treatment of Wolfram syndrome last week at the regenerative medicine symposium in Tokyo, Japan. Five faculty members from Washington University attended this important symposium. I got constructive feedback from the audience. To achieve a cure, we need to develop regenerative […]