Tag Archive for: patient-based therapeutics

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Combating Wolfram Syndrome

We have the pleasure of sharing the posts from Dr. Urano’s blog “Combating Wolfram Syndrome”.  Below are his posts for the week of July 21-25.

Friday, July 25, 2014

Endoplasmic Reticulum Disease Clinic 1

Thank you for your feedback for my blog.
http://wolframsyndrome.blogspot.com/2014/07/a-platform-for-providing-immediate-care_24.html
We need to consider multiple factors and logistics for establishing “Endoplasmic Reticulum Disease Clinic.” We need space, motivated physicians and nurses, and knowledgeable administrators. To accept out-of-state patients, we need to provide information and discount of hotels nearby. I feel that we can accomplish this.

Thursday, July 24, 2014

A Platform for Providing An Immediate Care for Patients 2

Thank you for your valuable feedback for my yesterday’s blog.
http://wolframsyndrome.blogspot.com/2014/07/a-platform-for-providing-immediate-care.htmlI feel that we need to create an interdisciplinary clinic where the integration of physicians across disciplines can lead to an improvement in the management of patients with Wolfram and Wolfram-related disorders (diseases related to ER stress). The key is that all the physicians are on the same floor and a patient can see them on the same day. I am working on a blueprint. Let’s call it “Endoplasmic Reticulum Disease Clinic“.

Wednesday, July 23, 2014

A Platform For Providing An Immediate Care for Patients 1 

I often think about this topic. What is the best platform for providing an immediate care for a patient with Wolfram and other rare diseases? My idea is to establish a multidisciplinary clinic for Wolfram and related diseases. When an undiagnosed patient comes to a hospital, he/she will see a medical geneticist/internist to get a correct diagnosis, and then a patient is referred to multiple specialists on the same floor. The key is that all the doctors are on the same floor so that a patient does not need to walk around a big medical center. I will keep on thinking about this. I welcome any feedback from you.

Tuesday, July 22, 2014

Please contact us if you receive a medicine for an “off-label” use

If you are a patient with Wolfram syndrome and have been prescribed a medicine for an “off-label” use, I would appreciate if you contact us (Phone: 314-362-8683, urano@dom.wustl.edu).
http://wolframsyndrome.dom.wustl.edu/As I mentioned in my previous blogs, the law let physicians prescribe a FDA-approved drug to treat a condition for which it is not approved. This is called an “off-label” use. Many physicians are compassionate, and try to help their Wolfram patients by prescribing a drug for an “off-label” use. I often get questions from physicians and patients related to an “off-label” use. Although I don’t recommend any specific FDA-approved drugs at the moment, I would gladly answer your questions. If you are receiving a drug for an off-label use, we can monitor biomarker levels for you and your physician. I respect your and your physician’s decision. So please contact us. I just want to help.

Monday, July 21, 2014

Consultation Clinic 2

As I mentioned in my previous blog, it would be important to establish a consultation clinic for Wolfram at Saint Louis Children’s Hospital for pediatric patients and at Barnes-Jewish Hospital for adult patients. We can do this using regular clinic space or set up new space. For the latter, we probably need to include other rare diseases into our platform. There are several advantages for this. My big idea is to set up a platform for regular care for patients with rare diseases.
http://wolframsyndrome.blogspot.com/2014/07/consultation-clinic.html

Photo of Dr. Fumihiko Urano Combating Wolfram Syndrome

Dr. Fumihiko Urano

Dr. 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.

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Patient-Based Therapeutics Part 5 – Wolfram Syndrome iPSCs

Wolfram Syndrome iPSCs

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

Photo of Dr. Fumihiko Urano

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.

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Research Reports From Washington University

Introducing… the Washington University Wolfram Syndrome Study Group!

By Dr. Tamara Hershey

Photo of Dr. Tamara Hershey

Dr. Tamara Hershey

I would like to tell you about the big picture of research and clinical activities at Washington University focused on Wolfram Syndrome. There are three parts to this effort 1) Diagnostic markers and treatment  development for Wolfram syndrome using animal models and human cells, led by Dr. Fumi Urano (see his previous blog postings here); 2) Patient-oriented natural history studies, led by me — Dr. Tamara Hershey) to determine the trajectory of Wolfram Syndrome-related neurological changes, providing the necessary background information for future clinical trials and 3) Expert clinical screening and care for Wolfram Syndrome, led by Dr. Bess Marshall. Dr. Marshall and other WU physicians now have the most in-depth clinical experience with Wolfram Syndrome in the nation and perhaps the world, providing the basis for a true clinical center of excellence.

Photo of Wash U Team of Drs.

(Left to Right): Dr. Fumihiko Urano, Dr. Tamara Hershey, and Dr. Bess Marshall

Fumi, Bess and I work as a team on all three of these aspects of Wolfram Syndrome research and care. We are in almost daily contact with each other to push our work further and problem solve together. It has been a privilege to work with both of them on something we are all so passionate about. In addition, we work with a large team of dedicated clinical and research faculty and staff, who we collectively refer to as the WU Wolfram Syndrome Study Group. Their names are below. I want you to know that there are a lot of talented and dedicated people here at WU working hard on the behalf of all Wolfram Syndrome families!

Photo of Dr. Timothy Barrett

Dr. Timothy Barrett

We are also in contact with collaborators across the world, including Dr. Tim Barrett in the UK and others, to pool our experimental and clinical data and share measurement tools and ideas. We hope that in the future, these collaborations will provide the basis for a multi-center international clinical trial network. We are committed to being ready to implement an efficient, high quality clinical trial, as soon as a safe drug is identified with strong experimental evidence suggesting that it might help.

WU Wolfram Syndrome Study Group Leaders:  F. Urano (Medicine), T. Hershey (Psychiatry, Radiology, Neurology) and B. Marshall (Pediatrics)  P. Austin, M.D. (Surgery) G. Earhart, Ph.D. (Physical Therapy) S. Eisenstein, Ph.D. (Psychiatry) J. Garbow (Radiology) J. Hoekel, O.D. (Ophthalmology) T. Hullar, M.D. (Otolaryngology) R. Karzon, Ph.D. (Audiology & Communication Sciences) H. M. Lugar, M.A. (Psychiatry) L. Manwaring, M.S. (Pediatrics) A. R. Paciorkowski, M.D. (Neurology, U Rochester) K. Pickett, Ph.D. (Physical Therapy) S. Ranck, MSW (Psychiatry) J. Rutlin, B.S. (Psychiatry) J. Shimony, M.D., Ph.D. (Radiology) A. Viehoever, M.D. (Neurology) N. H. White M.D., CDE (Pediatrics) In memoriam: A. Permutt, M.D. (Medicine) J. Wasson B.S. (Medicine)

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Diabetes, Wolframs and Botox, Oh My! – Lauren Gibilisco

Photo of Lauren Gibilisco

Lauren Gibilisco

Hello everyone.  My Botox surgery was a success.  I am happy to report that I am getting up only two or three times a night instead of every hour. I don’t feel as tired anymore through out the day.  This has made me feel so much better. I am able to drink a lot more and hold a lot more than every before.  This gives me a lot more energy so I can talk a lot more which is just what my mom needs. LOL.

I was also able to go back to my volunteer job this week where I shred paper.  Who better to shred confidential papers than someone who can’t see anything on them. ha-ha.  I’ve had this job since high school which I really enjoy.  The people there treat me like anyone else.  They don’t pity me.  In fact quite the opposite.  They love to give me a hard time and tease me.  It’s hard to know who is getting more harassed, them or me. My mouth is the only part of me that is not affected by WS.

I should back up and tell you a little about me.  I am affected by all aspects of DIDMOAD.  DI (DIABETES INSIPIDUS), DM (DIABETES MELLITUS), OA (OPTIC ATROPHY, D (DEAFNESS).  I am legally blind and use a cane to get around. I wear hearing aids for high frequency hearing loss. I was diagnosed with Diabetes Mellitus when I was two years old and take insulin shots.  The Diabetes Insipidus is controlled by medication. I take 20 prescription pills every day to control my WS. I was diagnosed with WS when I was 12. I have other symptoms but I will talk about them another day.

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Patient-Based Therapeutics Part 3

Research Update from
Dr. Fumihiko Urano

Patient-Based Therapeutics Part 3
Photo of Dr. Bess Marshall, Dr. Fumi Urano, Dr. Tamara Hershey

LEFT TO RIGHT: Dr. Bess Marshall, Dr. Fumi Urano, Dr. Tamara Hershey

Instead of introducing my research activities,  I would like to introduce my colleagues today. I have a lot of colleagues who have been helping me develop diagnostics and therapeutics for Wolfram at the Washington University Medical Center. Without their help, I cannot accomplish anything. I give many lectures and talks on Wolfram syndrome, but I feel that I am just a spokesperson or a salesman of our team.

Today I would like to introduce Dr. Bess Marshall and Dr. Tamara Hershey. Dr. Marshall is a pediatric endocrinologist and serves as a medical director of our annual Wolfram clinic. Dr. Marshall is an experienced, smart, and caring physician scientist. Dr. Hershey is a neuropsychologist and serves as a scientific director of our Wolfram clinic. Dr. Hershey is thoughtful, smart, and extremely good at getting things done. They are powerful driving force of our Wolfram project! I always appreciate their continuous support and advice. Here is their picture! (From left to right: Dr. Marshall, Fumi, and Dr. Hershey)

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.

 

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Research Update – Patient Based Therapeutics Part 1

Patient Based Therapeutics – Part 1

Photo of Dr. Fumihiko Urano

Dr. Fumihiko Urano

We are taking an unconventional approach to develop therapeutics for Wolfram syndrome. I would call it “patient-based therapeutics.” Our extensive molecular characterization of patient cells, especially iPSC-derived cells, has been providing us remarkable insights into the root cause of Wolfram syndrome. Based on these insights, I have been carefully choosing molecular targets and processes for developing therapeutics. These are the endoplasmic reticulum (ER) membrane integrity, ER calcium leakage, calpain-2, and WFS1 gene mutations.How we target WFS1 gene mutations? We have started testing genome editing to accomplish this. Genome editing is a process that involves cutting out pathogenic genetic material (i.e., mutations in the WFS1 gene) and replacing it with healthy genetic material. This is a molecular surgery. So I am becoming a molecular surgeon. In short, we are trying to repair a genetic defect in Wolfram syndrome.

Currently, we are repairing a genetic defect in iPS cells from patients with Wolfram syndrome to see if the molecular surgery can restore the normal function of neural progenitor cells derived from Wolfram iPS cells. This is an important step. When the transplantation of iPSC-derived retinal ganglion cells and beta cells are available in the clinic in the future, we need to repair the genetic defect before the transplantation.

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.

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