Why are we creating eye cells using skin cells from patients? More accurately, we are creating two different types of retinal cells using stem cells derived from skin fibroblasts of patients with Wolfram syndrome. We can immediately use these cells to understand the mechanisms of the disease and test the efficacy of candidate drugs. That’s a practical goal and should be achievable.
My audacious goal is to use these cells to replace damaged eye cells in patients. There are many theoretical and practical hurdles to accomplish this, but we should try. Every accomplishment starts with the decision to try.
http://thesnowfoundation.org/wp-content/uploads/2019/06/snow-foundation_logo.svg00Dr. Fumihiko Uranohttp://thesnowfoundation.org/wp-content/uploads/2019/06/snow-foundation_logo.svgDr. Fumihiko Urano2014-07-11 19:43:502020-09-07 20:10:39Why are we creating eye cells using skin cells from patients?
A Scientific Mind, a Tender Heart The Life of M. Alan Permutt, MD
Once asked why he had so many books documenting the trials and tribulations of people attempting to reach the peaks of some of the world’s tallest mountains, Dr. M. Alan Permutt replied that he enjoyed reading true stories about people overcoming great adversity.
J.T. Snow, Raquel Gebel and Dr. Permutt at the 2011 Casino Night.
Dr. Permutt speaking to the crowd at the 2011 Casino Night fundraiser benefiting the Snowman Fund.
While he never scaled a mountain himself, Dr. Permutt knew a thing or two about adversity. Diagnosed with juvenile diabetes as a teen, Permutt spent a lifetime managing a disease while becoming one of the nation’s leading diabetes researchers. Dr. Permutt, a Professor of Medicine and of Cell Biology and Physiology, and the former director of the Diabetes Research and Training Center, at Washington University School of Medicine, died on Sunday, June 10 at the age of 72 after a lengthy battle with cancer.
Dr. Permutt, born and raised in Birmingham, Alabama, was known for his enveloping warmth, outgoing personality, a laser-like scientific mind and dedication to his research. He was as comfortable discussing the minutia of cell biology as he was explaining his preferred method for grilling barbecue ribs. He enjoyed taking in the St. Louis Symphony as much as watching a football game over a corned beef sandwich at Lester’s Sports Bar. His love for his children and grandchildren knew no bounds.
Dr Alan Permutt MD JT Snow Stephany Snow -Gable
He was a respected teacher and mentor to medical residents and lab partners. Many colleagues without family in St. Louis were welcomed into his home to celebrate holidays and enjoy his popular dinner parties.
“I admired his continued passion for research, his tenacity to overcome adversities, imagination, drive, and innovation. I learned to be a scientist with Alan,” said Dr. Ernesto Bernal-Mizrachi, a former colleague in Dr. Permutt’s lab. “As a friend, he was truly precious and generous with my family and me. He was remarkably insightful, attentive, and invariably reflective and thoughtful.”
Dr. Permutt was an avid cyclist and work-out devotee – aerobics and Spinning classes were his favorites – who rarely missed a day of exercise prior to his illness. In 2009 he received the Active Living Award from Trailnet for his “indomitable spirit” and passionate promotion of physical activity as a primary treatment for diabetes.
“His force of will and implacable determination refused to allow diabetes to limit his aspirations, in work or play,” said friend and fellow cyclist David Howard. “Despite myriad responsibilities, he maintained a daunting regimen of exercise, honing his fitness on the bicycle to a remarkably high level.”
Dr. Permutt was an investigator or author for more than 200 publications on the genetic and physiological bases of diabetes, according to the medical database PubMed. He was a Howard Hughes Medical Investigator, and twice received the MERIT Status Award from the National Institute of Health, as well as several other distinguished awards relating to diabetes research. Last February, he received the prestigious Daniel P. Schuster Award for Distinguished Work in Clinical and Translational Science from the Washington University School of Medicine, among the highest honors the School of Medicine bestows on faculty.
One particularly significant contribution to medical science as the result of Dr. Permutt’s research team was the discovery of the Wolfram Syndrome gene in 1998. A rare genetic disorder that typically starts as Type 1 diabetes, the disease later deteriorates nerve cells in the eyes, ears and brain, usually resulting in death by age 30.
Years of lab work on Wolfram culminated in perhaps Dr. Permutt’s proudest professional achievement: two years into his cancer diagnosis, he was still able to bring together Wolfram Syndrome patients and their families for the first-ever multidisciplinary testing and assessment clinic in August 2010 in St. Louis.
The inaugural, and subsequent, groups of patients provided researchers with a significant amount of data to better understand the disease in the hopes of one day creating a treatment therapy. Because the disorder is so rare, it was the first time that Dr. Permutt and his researchers had actually met Wolfram patients. “For years,” Dr. Permutt said at the time, “I’ve been getting letters and e-mails from patients asking for help, and I’ve never been able to. It was very rewarding to finally be in a position to help.”
Dr. Permutt was preceded in death by his son, Alex; his mother Marguerite and father James Permutt, his stepmother Alva Shevin Permutt and his brother Stuart Shevin. Survivors include his daughters Joelle Permutt (Christopher Mumford) and Robin Winer (Todd), dear friend Rhea Oelbaum, grandchildren Abe, Eli, Benny and Alexi, sisters Patti (Jules) Wainger and Jan Shevin, and brother Maury Shevin.
In lieu of flowers, donations can be made in Dr. Permutt’s memory to a Wolfram Syndrome research foundation, the Jack and J.T. Snow Scientific Research Foundation, 17703 Gardenview Place Court, Glencoe, MO, 63038, or via www.thesnowfoundation.org
***When making a donation on PayPay, if you would like to add a message to the family, go to the section marked “Add special instructions to the seller”. This is where you can leave a note for the family. Thank you!
St. Louis’ CBS affiliate, KMOV, is a proud supporter of The Snow Foundation. Anchorman Steve Savard has been a longtime advocate and friend to our organization and supports our fight against Wolfram syndrome and diabetes in a variety of ways. Recently they have added our organization to the list of community partners they support throughout the year. We are very grateful for our friends at KMOV.
Here is more information about their program, KMOV Cares.
KMOV is devoted to making a difference in our community by partnering with nationally recognized and smaller local non-profit charities to aid the citizens of St. Louis.
KMOV is dedicated to bringing key issues in our community to light to make a difference. It is our mission to raise awareness through special broadcasts, news stories, public service announcements, web, mobile, and social media presence. Our award-winning journalists and staff strive to lend a helping hand. Plus, Steve Templeton’s 4 Degree Guarantee has generated over $31,550 in donations to date for our partners. More importantly KMOV has raised awareness for each organization, spurring even more donations, thanks to our viewers.
Dr. Fumihiko Urano Awarded Samuel E. Schecter Professorship in Medicine
Raquel Gebel and Dr. Fumihiko Urano at the Installation Ceremony
On Monday, April 1, 2013, Dr. Fumihiko Urano of the Washington University School of Medicine (WUSM) and renowned Wolfram syndrome researcher, was awarded the Samuel E. Schecter Professorship in Medicine. The event was held at the Eric P. Newman Education Center.
Dr. Urano is joined the faculty of Washington University School of Medicine as an Associate Professor of Medicine in the Division of Endocrinology, Metabolism and Lipid Research, and Director of the Wolfram Syndrome International Registry. Dr. Urano also holds a joint faculty appointment in the Department of Pathology and Immunology.
Stephanie Snow Gebel, Raquel Gebel, and Dr. Fumihiko Urano at Installation Ceremony.
A 1941 alumnus and professor emeritus of clinical medicine at Washington University School of Medicine, Samuel E. Schecter, M.D., established the Professorship of Medicine in 2002.
Dr. Schecter served in the U.S. Air Force during World War II and completed his residency in internal medicine at The Jewish Hospital in St. Louis. Dr. Schecter retired from private practice in 1991. In 2002 he received the School of Medicine’s 2nd Century Award, and later passed away in 2004. His Professorship in Medicine is one of the highest honors one can achieve at WUSM.
<h4 style=”font-weight: bold; color: #003c76; text-align: center;”><a href=”http://localhost:8888/snow-foundation/wp-content/uploads/2014/06/temp20140608_CoachSftblGm063-nfl_mezz_1280_1024.jpg”><img class=”aligncenter size-full wp-image-4336″ src=”http://localhost:8888/snow-foundation/wp-content/uploads/2014/06/temp20140608_CoachSftblGm063-nfl_mezz_1280_1024.jpg” alt=”temp20140608_CoachSftblGm063–nfl_mezz_1280_1024″ width=”960″ height=”678″ /></a></h4>
While in the midst of competing for roster spots and preparing for the 2014 NFL season during organized team activities, the Rams took a day for a different type of competition. In a charity event that doubles as a camaraderie-building experience during the NFL offseason, 22 Rams players took part in Head Coach Jeff Fisher’s annual softball game on Sunday.
Played at GCS Ballpark in Sauget, Ill., for the third straight year, the game featured all the hijinks typical of Fisher’s yearly event, complete with a 3-0 lead before the game’s first pitch, cheerleaders as base runners, mascots as pitchers and the opposing team beginning an inning with two outs. Pitted against a team assembled by offensive coordinator Brian Schottenheimer, Fisher found his team in an unfamiliar spot, trailing often before rallying late. The game ended in a 22-22 tie after eight innings, continuing Fisher’s string of games without a loss.
“We had to get ourselves back in it,” Fisher said. “I had to give Coach Schottenheimer some applause, they did a nice job, so we walked off tied.”
Fisher continued his tradition of bringing celebrity guests with area ties for a third straight year. Among the guests this year was Grammy Award winning hip-hop artist and St. Louis native Murphy Lee, who also participated in the event’s home run derby, won by Rams LB <a class=”player-card-tooltip” style=”font-weight: bold; color: #00295b;” title=”James Laurinaitis” href=”http://www.stlouisrams.com/team/roster/james-laurinaitis/72120770-25b2-4fb2-9b56-10ca0d8067b9/” rel=”/cda-web/person-card-module.htm?mode=data&id=72120770-25b2-4fb2-9b56-10ca0d8067b9″ rev=”player”>James Laurinaitis<img src=”http://www.stlouisrams.com/assets/nflimg/icon-article-link.gif” alt=”” /></a>.
The “Coach Fisher and Friends” softball game has been a tradition for Fisher that dates back to his days as the head coach of the Tennessee Titans, and the event has supported a litany of charities since its inception. This year’s event included a player from those Tennessee days, in new Rams receiver <a class=”player-card-tooltip” style=”font-weight: bold; color: #00295b;” title=”Kenny Britt” href=”http://www.stlouisrams.com/team/roster/kenny-britt/ded52e21-7894-4369-ba1a-95c64129282d/” rel=”/cda-web/person-card-module.htm?mode=data&id=ded52e21-7894-4369-ba1a-95c64129282d” rev=”player”>Kenny Britt<img src=”http://www.stlouisrams.com/assets/nflimg/icon-article-link.gif” alt=”” /></a>, who delivered a two-run home run in the game.
The game featured more than 4,000 fans in attendance, and benefited five charities: The Wounded Warrior Project, The Backstoppers, Mercy Ministries, The Catch-A-Dream Foundation and The Jack and J.T. Snow Scientific Research Foundation. The Snow foundation, founded in part in memoriam of former Rams receiver and broadcaster Jack Snow, teams with Washington University’s medical research team to raise awareness for Wolfram syndrome, a rare form of diabetes.
While the game is certainly a benefit to the charities involved, they weren’t the only ones to gain from the event as a whole. The Rams raffled off the players’ game worn jerseys to fans in attendance and also held a silent auction featuring NFL memorabilia. Fans were also treated to a post-game fireworks show.
“It’s a big thing for the charities, but it’s also a fun evening—it’s a blast,” Fisher said. “People tell friends, and they tell friends, and they just keep coming out.”
<h4 style=”color: #003c76; text-align: center;”>Check out the 2013 St. Louis Rams video about the event <a style=”color: #003c76;” href=”http://www.stlouisrams.com/media-center/videos/Coach-Fisher–Friends-Celebrity-Softball-Game/b0ec045f-84fc-46f2-8bc3-f1b2efcfe7b8″ target=”_self”>HERE</a></h4>
<h2 style=”text-align: center;”></h2>
As I mentioned in my previous blogs, we have identified three FDA-approved drugs, one supplement, and new groups of drugs that can potentially delay the progression of Wolfram syndrome. We have been testing the efficacy of these drugs in cells from patients and two animal models of Wolfram syndrome. Preliminary data look good, and we have been working very hard to bring at least one drug to patients.
We have also identified a potential biomarker that would be useful for monitoring the efficacy of our new treatment. I would like to thank patients who donated blood samples to us. Recently, some families donated blood samples from patients’ siblings, and these samples were really helpful to confirm our findings.
I have been trying to establish firm relationships with biotech companies and nonprofit organizations to bring these drugs to our patients through clinical trials. Our lawyers have been helping us a lot. I will keep on pushing the envelope with my wonderful team and colleagues.
Dr. Fumihiko Urano
Dr. Fumihiko Urano is a renowned physician and scientist developing therapeutics and diagnostics for Wolfram syndrome and juvenile onset diabetes. His areas of expertise include Wolfram syndrome, type 1 diabetes, Pediatric pathology and genetics and Molecular Endocrinology. He is currently employed at the Washington University School of Medicine where he holds the Samuel E. Schechter Professor of Medicine, 2012 – present.
http://thesnowfoundation.org/wp-content/uploads/2019/06/snow-foundation_logo.svg00Dr. Fumihiko Uranohttp://thesnowfoundation.org/wp-content/uploads/2019/06/snow-foundation_logo.svgDr. Fumihiko Urano2014-04-24 20:03:042020-09-07 20:10:39Patient Based Therapeutics – New Drug Candidates
I received many emails regarding our progress on Wolfram syndrome induced pluripotent stem cells (iPS cells) in the past two weeks. I would like to update you on a few things. As I mentioned in my previous blogs, we have created many iPS cells from skin cells of patients with Wolfram syndrome. These iPS cells can differentiate into various types of cells including brain cells and pancreatic beta cells that are damaged in patients with Wolfram syndrome
1. Disease modeling
We could successfully differentiate these iPS cells into neural progenitor cells. These are immature brain cells. We found that neural progenitor cells from patients are not completely damaged, which was surprising, but good news to us. Instead, they have altered calcium homeostasis. My impression right now is that cells from patients with Wolfram syndrome are “sensitive” to environmental stress, especially stimulus that changes cellular calcium levels. So we are looking for drugs that can modulate calcium homeostasis in cells to develop a treatment for Wolfram syndrome.
2. Testing drugs
As I mentioned above, we are focusing on drugs that can modulate calcium homeostasis in cells, especially endoplasmic reticulum calcium levels, to develop a treatment. Three drugs out of five candidate drugs that we have identified so far can control endoplasmic reticulum calcium levels. We are testing these three drugs using iPS cells.
3. Correcting a mutation
Using a special enzyme and artificial DNA, we are replacing an abnormal segment of Wolfram gene with a normal segment of Wolfram gene in patient-derived iPS cells. In theory, we should be able to correct altered calcium homeostasis through this process.
4. Making eye cells
A group in Columbia University Medical Center in New York could successfully make pancreatic beta cells from Wolfram syndrome iPS cells. We are collaborating with this group. So we are focusing our own efforts on making eye cells from Wolfram syndrome iPS cells. This is a collaboration project with a group in a major medical center in Japan. They have a special “recipe” for making eye cells. Because a clinical trial using this technology for an eye disease will start in a few weeks in Japan, I feel that this collaboration is so important for us. A physician and scientist who is working on this collaboration project will come to the US and work with us in a few months. The arrangement has been made, and the Japanese agency will partially support this effort.
Dr. Fumihiko Urano is a renowned physician and scientist developing therapeutics and diagnostics for Wolfram syndrome and juvenile onset diabetes. His areas of expertise include Wolfram syndrome, type 1 diabetes, Pediatric pathology and genetics and Molecular Endocrinology. He is currently employed at the Washington University School of Medicine where he holds the Samuel E. Schechter Professor of Medicine, 2012 – present.
All of the people working on the Wolfram studies at Washington University are grateful every day for the support of the Snow Foundation and all of the other groups that support our work. The Washington University Wolfram Study group is continuing to work on analyzing the data that we have and to plan for collecting data that we still are lacking to come up with a reliable way to track progression of Wolfram Syndrome so that we will be prepared to be able to determine whether any intervention is helping. Although we don’t yet have an intervention, we are hopeful that that day is not far off when we begin an intervention trial. We are also accumulating as much information as we can to help provide recommendations for clinical care until that day arrives. I am happy to provide letters to anyone with Wolfram who needs help with insurance, work, school, or disability issues, just contact me at marshall@kids.wustl.edu.
All the best to our good friends in the Wolfram community!
Dr. Marshall’s research interests have included intermediary carbohydrate metabolism, glucose transporter structure and function, and metabolic engineering to alter insulin resistance. She is currently funded by a National Institutes of Health Clinician-Investigator Development award, the Diabetes Research and Training Center, and is a scholar of the Child Health Research Center of Excellence in Developmental Biology at Washington University. Dr. Marshall’s clinical interests include all aspects of endocrinology and metabolism.
http://thesnowfoundation.org/wp-content/uploads/2019/06/snow-foundation_logo.svg00The Snow Foundationhttp://thesnowfoundation.org/wp-content/uploads/2019/06/snow-foundation_logo.svgThe Snow Foundation2014-03-27 00:26:162020-09-07 20:10:39A Word From the Wolfram Study Group
Today I would like to discuss how we use induced pluripotent stem cells (iPS cells) derived from patients with Wolfram syndrome for developing treatment. Our group as well as a group in Columbia University have created iPS cells from patients with Wolfram syndrome.What are induced pluripotent stem cells (iPS cells)?
iPS cells are a type of stem cells that can be generated directly from adult cells, including skin cells. We can make pancreatic beta cells and neurons from these iPS cells.How can we use Wolfram syndrome iPS cells for treatment?
We can expect that Wolfram syndrome patients iPS cell lines and Wolfram iPS cell-derived beta cells to be a cornerstone for developing novel therapeutic modalities for Wolfram syndrome and other diseases involving endoplasmic reticulum (ER) dysfunction. We can utilize these cells to screen and identify drugs for treating patients with Wolfram syndrome and other ER-associated diseases.Regenerate Damaged Tissues
In the future, we can utilize these cells to regenerate damaged tissues including pancreatic beta cells, retinal ganglion cells (eye cells), and neurons in patients with Wolfram syndrome. Rapid progress in genetic editing technologies and regenerative medicine will make it possible to correct WFS1 mutations in patient-specific iPSC lines and regenerate patients’ damaged cells. Our current progress:
1. Using these Wolfram iPS cells, we have identified a drug target for developing treatment (our manuscript is in review.)
2. As I reported before, we are currently testing the efficacy of five different drugs using iPS cell-derived neurons.
3. We are correcting a WFS1 gene mutation by genetic editing and making eye cells using these iPS cells.We should make the best use of these cells to develop treatments for Wolfram syndrome, efforts that may lead to breakthroughs in diabetes treatment. I have articulated my strategy in the article just published in Diabetes. http://diabetes.diabetesjournals.org/content/63/3/844.full
Dr. Fumihiko Urano
Dr. Fumihiko Urano is a renowned physician and scientist developing therapeutics and diagnostics for Wolfram syndrome and juvenile onset diabetes. His areas of expertise include Wolfram syndrome, type 1 diabetes, Pediatric pathology and genetics and Molecular Endocrinology. He is currently employed at the Washington University School of Medicine where he holds the Samuel E. Schechter Professor of Medicine, 2012 – present.
Patient-Based Therapeutics Part 4 – Drug Screening Progress
Based on the data obtained from our patients, animal models, and cell models of Wolfram syndrome, we found that calcium depletion of the endoplasmic reticulum (ER) plays a role in the pathogenesis of Wolfram syndrome. So we have been looking for drugs that can prevent ER calcium-depletion-mediated cell death. As of today, we have found 4 FDA-approved drugs (currently used for other diseases), one supplement, and a new category of drugs (not approved by the FDA). One of the FDA-approved drugs can prevent ER calcium-depletion and cell death in the tissue culture dish. It seems like that this drug can relieve ER stress in one animal model of Wolfram syndrome. We are working very hard to complete these preclinical studies. The ER calcium-depletion releases a molecule called MANF from the ER to the circulation. So we are carefully monitoring levels of MANF in human blood samples.
So how long will it take to bring one of these drugs to our patients? I would like to share a few thoughts.
1. There is no guarantee that these drugs will work in our patients.
2. It is a little challenging for me to predict exactly how long it will take to bring these drugs to our patients.
3. However, I have a clear plan, and am doing my best to make it happen.
Dr. Fumihiko Urano a renowned physician and scientist developing therapeutics and diagnostics for Wolfram syndrome and juvenile onset diabetes. His areas of expertise include Wolfram syndrome, type 1 diabetes, Pediatric pathology and genetics and Molecular Endocrinology. He is currently employed at the Washington University School of Medicine where he holds the Samuel E. Schechter Professor of Medicine, 2012 – present.
A Few weeks ago, a young woman who had been battling Wolfram syndrome for many years passed away. Everyone knew, loved and supported her. Below is a touching blog post from Washington University School of Medicine’s Dr. Fumihiko Urano about our friend, Ms. K.
In Memory of K
Yesterday I was heartbroken because I learned of the death of Ms. K, a young woman with Wolfram syndrome. I was not helpful. I could not even find a way to delay the progression of the disease. I felt devastated. I really felt devastated. I was very sad and could not respond to any emails for several hours.
As a person, I sometimes feel scared. Although I am always doing my best and determined to figure out a way to help patients with Wolfram syndrome, I know that I am not a god. The treatment I am planning to test may not be effective. I often wake up at midnight and feel scared. However, as a physician, I swear to figure out a way to stop the progression of Wolfram syndrome, find a way to regenerate damaged tissues, and give patients hope. I think I should keep on running to figure out a way to help patients with Wolfram syndrome.
I saw Ms. K reading a poem entitled a single second in time, which reminded me of Sam Berns, a wonderful young man with progeria, a rare disease characterized by accelerated aging. Sam passed away earlier this year. Although he was much younger than myself, I learned a lot from him and his interviews. You may want to watch the following video and read Dr. Francis Collin’s blog on him. His philosophy for a happy life is a wonderful piece to watch. Take care everyone, and have a nice weekend. I will appreciate a single second in time just like Ms. K.
http://thesnowfoundation.org/wp-content/uploads/2019/06/snow-foundation_logo.svg00Dr. Fumihiko Uranohttp://thesnowfoundation.org/wp-content/uploads/2019/06/snow-foundation_logo.svgDr. Fumihiko Urano2014-02-28 23:52:472020-09-07 20:10:40In Memory of K by Dr. Fumihiko Urano
Why are we creating eye cells using skin cells from patients? More accurately, we are creating two different types of retinal cells using stem cells derived from skin fibroblasts of patients with Wolfram syndrome. We can immediately use these cells to understand the mechanisms of the disease and test the efficacy of candidate drugs. That’s a practical goal and should be achievable.
You must be logged in to post a comment.