tag:blogger.com,1999:blog-22275488991523323832024-03-12T19:51:59.312-05:00Combating Wolfram SyndromeAnonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comBlogger236125tag:blogger.com,1999:blog-2227548899152332383.post-49083670572417915222014-11-15T09:58:00.004-06:002014-11-15T09:58:55.239-06:00Moving to the Washington University Medical Center website<span style="font-size: large;">Dear Friends,</span><br />
<span style="font-size: large;"><br /></span>
<span style="font-size: large;">We are moving to the Washington University Medical Center website. We will make the most informative and helpful web for our patients, families, physicians, researchers, and general public. We will closely work with patient organizations.</span><br />
<span style="font-size: large;"><br /></span>
<span style="font-size: large;">Information about Wolfram syndrome</span><br />
<a href="http://wolframsyndrome.dom.wustl.edu/"><span style="font-size: large;">http://wolframsyndrome.dom.wustl.edu/</span></a><br />
<span style="font-size: large;">My blog</span><br />
<a href="http://wolframsyndrome.dom.wustl.edu/dr-uranos-blog/"><span style="font-size: large;">http://wolframsyndrome.dom.wustl.edu/dr-uranos-blog/</span></a><br />
<span style="font-size: large;"><br /></span>
<span style="font-size: large;">Please feel free to contact me if you have any questions.</span><br />
<span style="font-size: large;">urano@dom.wustl.edu</span><br />
<span style="font-size: large;">314-362-8683</span><br />
<span style="font-size: large;"><br /></span>
<span style="font-size: large;">Fumi Urano</span><br />
<span style="font-size: large;">Kindest regards,</span><br />
<span style="font-size: large;"><br /></span>
<br />Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-69522923208434895982014-11-14T08:13:00.002-06:002014-11-14T08:13:49.144-06:00Wolfram syndrome website at Washington University Medical Center<span style="font-size: large;">We have created an website specifically designed for Wolfram syndrome patients, families, physicians, and researchers. Our aim is to create the most useful and informative site and platform for patients with Wolfram syndrome. We plan to keep on adding information to this site.</span><br />
<a href="http://wolframsyndrome.dom.wustl.edu/"><span style="font-size: large;">http://wolframsyndrome.dom.wustl.edu/</span></a><br />
<span style="font-size: large;"><br /></span>
<span style="font-size: large;">Most of my previous blogs have been transferred to this site. I plan to move my blog there.</span><br />
<a href="http://wolframsyndrome.dom.wustl.edu/dr-uranos-blog/"><span style="font-size: large;">http://wolframsyndrome.dom.wustl.edu/dr-uranos-blog/</span></a><br />
<span style="font-size: large;"><br /></span>
<span style="font-size: large;">The site is managed by a wonderful information technology specialist. I cannot thank you enough for her efforts.</span><br />
<span style="font-size: large;"><br />Kindly,</span><br />
<span style="font-size: large;">Fumi Urano</span>Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-87680880074952380302014-11-14T07:55:00.001-06:002014-11-14T07:56:15.649-06:00Insulin-producing cells and brain cells in Wolfram syndrome<span style="color: #444444; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: medium;"><span style="background-color: white;">In Wolfram syndrome, insulin-producing pancreatic beta cells and brain cells selectively degenerate. Other cells, such skin cells and immune cells, are healthy. Why </span></span><span style="background-color: white; color: #444444; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: medium;">are</span><span style="background-color: white; color: #444444; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: medium;"> beta cells and brain cells so sensitive to the loss of function of Wolfram gene?</span><br />
<span style="background-color: white; color: #444444; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: medium;"><br /></span>
<span style="background-color: white; color: #444444; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: medium;">It has been recently suggested that beta cells and brain cells have many common features. My hunch is that brain cells and brain-like cells, including beta cells, are sensitive to dysregulated calcium homeostasis. So if we can modulate cellular calcium homeostasis using small molecules, we can potentially delay the progression of Wolfram syndrome. We have preclinical data supporting this model. We can disclose the information soon.</span><br />
<span style="background-color: white; color: #444444; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: medium;"><br /></span>
<span style="background-color: white; color: #444444; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: medium;">Thank you for reading this. I hope you have a wonderful day.</span><br />
<span style="background-color: white; color: #444444; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: medium;"><br /></span>
<span style="background-color: white; color: #444444; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: medium;">Kindly,</span><br />
<span style="background-color: white; color: #444444; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: medium;">Fumi Urano</span><br />
<a href="http://wolframsyndrome.dom.wustl.edu/" style="background-color: white; color: #4d469c; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 13px; line-height: 18.2000007629395px; text-decoration: none;"><span style="font-size: medium;">http://wolframsyndrome.dom.wustl.edu/</span></a>Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-54151513455311343682014-11-13T08:04:00.003-06:002014-11-13T08:04:40.161-06:00Dr. Banting<span style="font-size: large;">Today is our Diabetes Research Center's Diabetes Day. We will present our progress on the development of therapeutics and diagnostics for Wolfram syndrome.</span><br />
<span style="font-size: large;"><br /></span>
<span style="font-size: large;">The father of diabetes research is Dr. Banting who discovered insulin. His research led to the insulin therapy for patients with diabetes. Here is an interesting blog about him.</span><br />
<a href="http://diabetesdad.org/2014/11/12/this-man-saved-your-your-childs-life-what-do-you-know-about-him/"><span style="font-size: large;">http://diabetesdad.org/2014/11/12/this-man-saved-your-your-childs-life-what-do-you-know-about-him/</span></a><br />
<span style="font-size: large;"><br /></span>
<span style="font-size: large;">I hope you have a wonderful day.</span><br />
<span style="font-size: large;"><br /></span>
<span style="font-size: large;">Kindest regards,</span><br />
<span style="font-size: large;">Fumi Urano</span><br />
<a href="http://wolframsyndrome.dom.wustl.edu/"><span style="font-size: large;">http://wolframsyndrome.dom.wustl.edu/</span></a>Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-24014942037212240322014-11-12T07:30:00.001-06:002014-11-12T07:37:29.997-06:00Brain Functions and Medication<span style="font-size: large;">Patients with Wolfram syndrome face multiple challenges in addition to diabetes. That's why I always feel that Wolfram is the most difficult form of diabetes. Mood swings, anxiety, and depression are commonly seen. Although the molecular mechanisms underlying these symptoms are not clear, we assume that these are related to the dysregulation of neurotransmitter secretion. Endoplasmic reticulum is involved in the maturation and secretion of secreted factors in the brain cells, and Wolfram protein is localized to the endoplasmic reticulum and secretory granules.</span><br />
<div>
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<span style="font-size: large;">Because Wolfram is diabetes with brain cell dysfunction, our candidate drugs should pass the blood-brain barrier. Many drugs cannot reach the brain because blood vessels in the brain have a special structure called the blood-brain barrier. I always make sure that our candidate drugs pass the blood-brain barrier and reach brain cells. </span></div>
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<span style="font-size: large;">Thank you for reading this. I would like to send kind thoughts toward you. I would like you to stay optimistic. Thank you again.</span></div>
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<span style="font-size: large;"><br /></span></div>
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<span style="font-size: large;">Take care,</span></div>
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<span style="font-size: large;">Fumi Urano</span></div>
Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-39802141352143560982014-11-11T08:23:00.001-06:002014-11-11T08:23:28.110-06:00Please help us spread the word<span style="font-size: large;">There is an urgent need to develop therapeutics for Wolfram syndrome. We need to swiftly test the safety of each new treatment and bring it to patients. I hope you share the video and help us spread the word.</span><br />
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<a href="https://www.facebook.com/video.php?v=948926448455453"><span style="font-size: large;">https://www.facebook.com/video.php?v=948926448455453</span></a></div>
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<span style="font-size: large;"><br /></span></div>
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<span style="font-size: large;">I am interested in donating my intellectual properties to patient organizations. A clinical trial for new treatment is controlled by a pharmaceutical company or an investigator who owns the intellectual property of the treatment/drug. If a patient organization owns it, they can control the clinical trial and potentially get some income out of it. They can use the money for developing new therapies or raising awareness.</span></div>
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<span style="font-size: large;">Thank you for reading this. I always appreciate your continued encouragement and support. I read all the emails with gratitude. I cannot thank you enough.</span></div>
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<span style="font-size: large;"><br /></span></div>
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<span style="font-size: large;">Warmest regards,</span></div>
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<span style="font-size: large;">Fumi Urano</span></div>
<div>
<a href="http://wolframsyndrome.dom.wustl.edu/">http://wolframsyndrome.dom.wustl.edu/</a></div>
Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-26427372382395249872014-11-10T07:30:00.001-06:002014-11-10T07:30:45.209-06:00Intervention and Platform<span style="font-size: large;">My team is pursuing multiple therapeutic modalities, including therapies using FDA-approved drugs (drug repurposing), combination therapies, new small molecules, and stem cell-based therapy combined with genome editing. I am also working hard to create platforms to bring these new therapies to patients. Both should happen simultaneously.</span><br />
<span style="font-size: large;"><br /></span>
<span style="font-size: large;">Thank you for reading this blog. I feel something wonderful is going to happen to us today.</span><br />
<span style="font-size: large;"><br /></span>
<span style="font-size: large;">Warmest regards,</span><br />
<span style="font-size: large;">Fumi Urano</span>Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-32962130269163432642014-11-09T08:18:00.001-06:002014-11-09T08:18:48.209-06:00Combination therapy<span style="font-size: large;">My team's new initiative is to develop a "combination therapy" for Wolfram and Type 1 diabetes. What is a "combination therapy"? It is a therapy that uses more than one medication or modality. The advantage for this is that we can target different enzymes involved in the disease progression, which may increase our chance of stopping the progression. We may be able to decrease the dose of each drug, which reduces the risk of side effects. The challenge is that we don't know which combination is the best. It is almost like solving the puzzle, but we will keep on trying.</span><div>
<span style="font-size: large;"><br /></span></div>
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<span style="font-size: large;">Thank you for reading this. I hope you have a wonderful Sunday.</span></div>
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<span style="font-size: large;"><br />Warmest regards,</span></div>
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<span style="font-size: large;">Fumi Urano</span></div>
Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-39615846102196519882014-11-08T09:45:00.001-06:002014-11-08T09:47:18.807-06:00Other symptoms and an urgent need<span style="font-size: large;">Wolfram syndrome is characterized by juvenile-onset diabetes and optic nerve atrophy. Many patients experience diabetes insipidus, hearing impairment, and ataxia due to neurodegeneration. You can find these symptoms in a text book or review articles.</span><br />
<span style="font-size: large;"><br /></span>
<span style="font-size: large;">There are other common symptoms that have not been extensively studied. Here is the list of symptoms based on our database. More than 10% of patients experience the following. You will find how difficult this disorder is. <b>There is an urgent need to develop therapeutics for Wolfram syndrome.</b> We need <b>drugs</b> and <b>stem cell-based therapy in combination with gene therapy</b>. </span><br />
<span style="font-size: large;"><br /></span>
<span style="font-size: large;">Neurogenic Bladder: 25.00%</span><br />
<span style="font-size: large;">Anxiety: 25.00%</span><br />
<span style="font-size: large;">Headaches: 25.00%</span><br />
<span style="font-size: large;">Problems Regulating Temperature: 22.50%</span><br />
<span style="font-size: large;">Bladder Incontinence: 17.50%</span><br />
<span style="font-size: large;">Apnea: 15.00%</span><br />
<span style="font-size: large;">Dizziness When Standing Up: 15.00%</span><br />
<span style="font-size: large;">Postural Instability (this is related to ataxia, but just in case): 12.50%</span><br />
<span style="font-size: large;">Hypogonadism: 12.50%</span><br />
<span style="font-size: large;">Seizures: 12.50%</span><br />
<span style="font-size: large;">Constipation/Fecal Impactation: 12.50%</span><br />
<span style="font-size: large;">Panic Attacks: 10.00%</span><br />
<span style="font-size: large;">Weight Loss: 10.00%</span><br />
<span style="font-size: large;">Excessive Sweating<span class="Apple-tab-span" style="white-space: pre;"> </span>: 10.00%</span><br />
<span style="font-size: large;"><br /></span>
<span style="font-size: large;">I would like to donate the entire data in our registry database to the patient organizations. I feel patients should own the data collected from patients.</span><br />
<span style="font-size: large;"><br /></span>
<span style="font-size: large;">Although these symptoms sound awful, I am still hopeful. We are making steady progress. I believe in the power of genetic medicine. I always appreciate support from our patients and families, patient organizations, our colleagues in St. Louis, US, England, Europe, South America, and Asia. I feel grateful. Thank you, Thank you, Thank you.</span><br />
<span style="font-size: large;"><br /></span>
<span style="font-size: large;">Kindest regards,</span><br />
<span style="font-size: large;">Fumi Urano</span>Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-46185625170997534822014-11-07T08:21:00.001-06:002014-11-07T08:21:32.208-06:00Thank you, Thank you, Thank you for your support.<span style="font-size: large;">I receive many emails and phone calls from patients with genetic disorders, including Wolfram syndrome, and diabetes. Most of them have questions related to their conditions. I also receive thank-you letters. I appreciate all of these emails, phone calls, and letters. I always learn some thing out of these. </span><br />
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<span style="font-size: large;"><br /></span></div>
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<span style="font-size: large;">Our therapeutic development is largely supported by donations from patient organizations, patients, and their family members and friends. <a href="http://thesnowfoundation.org/" target="_blank">The Jack and JT Snow Foundation</a> has been supporting my team since I joined <a href="http://wolframsyndrome.dom.wustl.edu/" target="_blank">Washington University Medical Center</a> in 2012. Recently <a href="http://elliewhitefoundation.org/" target="_blank">the Ellie White Foundation </a>has started supporting my team. The team Alejandro and the team Ian also started supporting us. I also receive individual donations all the time. Patient organizations <a href="http://www.didmoad.org/" target="_blank">in the US</a> and <a href="http://www.wolframsyndrome.co.uk/index.html" target="_blank">UK</a> are raising awareness. I cannot thank you enough. I feel grateful.</span></div>
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<span style="font-size: large;"><br /></span></div>
<div>
<span style="font-size: large;">I read <a href="http://thesnowfoundation.org/living-wolfram-syndrome-lauren-gibilisco-12/" target="_blank">the blog written by Lauren</a>, one of our patients, yesterday and was struck by that. I hope you will read this. </span></div>
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<span style="font-size: large;"><br /></span></div>
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<span style="font-size: large;">Thank you for your support. I feel grateful. Thank you, Thank you, and Thank you.</span></div>
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<span style="font-size: large;">Take care,</span></div>
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<span style="font-size: large;">Fumi Urano</span></div>
Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-55722482683615659942014-11-06T07:14:00.002-06:002014-11-06T07:21:50.622-06:00Safety<span style="font-size: large;">We have identified a few small molecules (i.e., drugs) that can potentially delay the progression of Wolfram syndrome. Our current focus is to make sure these drugs are safe. Ultimately, we need to confirm the safety in patients <a href="http://wolframsyndrome.dom.wustl.edu/" target="_blank">by conducting dose escalation studies</a>. </span><br />
<span style="font-size: large;"><br /></span><span style="font-size: large;">I had productive discussions yesterday. Both meetings were fruitful. I feel hopeful today. Thank you so much for your support and encouragement.</span><br />
<span style="font-size: large;"><br /></span>
<span style="font-size: large;">Warmly,</span><br />
<span style="font-size: large;">Fumi Urano</span>Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-70988800580812363062014-11-05T07:27:00.001-06:002014-11-05T07:49:21.492-06:00One day living with juvenile diabetes<span style="font-size: large;">Our teammate, Mrs. Pat Gibilisco, who runs <a href="http://www.didmoad.org/" target="_blank">our patient supporting group web</a> introduced us <a href="https://www.youtube.com/watch?v=gngHzRcBpKI&feature=youtu.be" target="_blank">a very important short video</a>. </span><br />
<span style="font-size: large;"><br />
This short video describes "one day" of a 7-year-old boy with juvenile diabetes. As many of you are aware, <b>chronic disease never leaves you</b>. You need to live with it 24/7. You can't take a break even on Sundays and holidays. We need to educate patients how to live with it, but what we really want is to provide a cure. It is not easy, but I always believe <a href="http://wolframsyndrome.dom.wustl.edu/" target="_blank">that's what we should pursue</a>. </span><br />
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Thank you for reading this. I will have very important meetings today and I am hopeful. </span><br />
<span style="font-size: large;"><br />Kindest regards,</span><br />
<span style="font-size: large;">Fumi Urano</span>Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-84150623050517202162014-11-04T06:54:00.000-06:002014-11-05T04:39:43.541-06:00Raise Awareness for the younger generation<span style="font-size: large;">Mrs. Stephanie Snow Gebel, my teammate and the driving force for our Wolfram syndrome research, gave a presentation on Wolfram syndrome and juvenile diabetes for 600 children yesterday. It was successful. She has been helping us raise awareness and raise funds for therapeutic development. It is important to raise awareness for the younger generation of rare diseases and other medical conditions. We will keep on raising awareness of Wolfram syndrome. We need HOPE to move forward.</span><br />
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<span style="font-size: large;">Thank you for visiting this website. I am sending kind thoughts toward you.</span><br />
<span style="font-size: large;"><br /></span>
<span style="font-size: large;">Kindly,</span><br />
<span style="font-size: large;">Fumi Urano</span>Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-33924931330848088822014-11-03T08:14:00.001-06:002014-11-03T08:14:25.751-06:00Thank you, Wolfram syndrome UK<span style="font-size: large;">Wolfram syndrome UK just hosted a successful 'A Night at the 80's' event! They have been working very hard to raise awareness and funds for combating Wolfram syndrome. I look forward to meeting with them soon. </span><br />
<a href="http://www.wolframsyndrome.co.uk/index.html"><span style="font-size: large;">http://www.wolframsyndrome.co.uk/index.html</span></a><br />
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<span style="font-size: large;">I hope you have a wonderful Monday. Thank you for reading my blogs. I appreciate your support, suggestions, and encouragement. </span><br />
<span style="font-size: large;"><br /></span>
<span style="font-size: large;">Kindly,</span><br />
<span style="font-size: large;">Fumihiko (Fumi) Urano</span>Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-83793243939082420222014-11-02T06:36:00.000-06:002014-11-02T06:40:21.378-06:00A platform to inject stem cell-derived cells or trophic factors<span style="font-size: large;">We have started a workgroup whose main purpose is to create a practical clinical platform to inject stem cell-derived cells or drugs stereotactically into human patients with degenerative disorders, including Wolfram syndrome, as a therapy. We will also discuss the merits of one therapeutic strategy over another as well. Our focus is the physical, infrastructural, and regulatory aspects of achieving this. I will work with prominent neurosurgeons. More to come. <a href="http://wolframsyndrome.dom.wustl.edu/">http://wolframsyndrome.dom.wustl.edu/</a></span><br />
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<span style="font-size: large;">Thank you for reading this. I feel hopeful. Have a beautiful Sunday. Wishing you A happy week ahead. Kindly, Fumi</span><br />
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Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-48366310078149215042014-11-01T09:11:00.002-05:002014-11-01T19:04:05.125-05:00Think ahead for transplantation<span style="font-size: large;">I was speaking with my good friend in neurosurgery last night. We talked about the injections of trophic factors and stem cell-derived brain cells into patients with Wolfram syndrome and other degenerative disorders. Our conclusion is that we should start preparing for these now. We need a CLIA-Certified facility to create <b>stem cells using patients' skin cells (<u>not the embryonic stem cells</u>)</b> and stem cell-derived brain cells and eye cells. We need devices for injections of trophic factors and stem cell-derived brain cells. We need to think ahead. The stem cell-based therapy group started last night. <a href="http://wolframsyndrome.dom.wustl.edu/">http://wolframsyndrome.dom.wustl.edu/</a></span><br />
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<span style="font-size: large;">Thank you for reading this blog. I hope you have a wonderful weekend. I feel empowered today. Kindly, Fumi Urano</span>Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-10755580983443310962014-10-31T06:37:00.003-05:002014-10-31T06:49:13.271-05:00Q&A Wolfram syndrome<span style="font-family: Times, Times New Roman, serif; font-size: large;">Here are the questions I often get. There is currently no effective treatment for Wolfram syndrome, creating <b>an urgent need to develop novel therapeutics</b>. Our current strategy is to delay the progression of common manifestations using small molecules (i.e., drugs), and then develop stem cell-based therapies.</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><a href="http://wolframsyndrome.dom.wustl.edu/">http://wolframsyndrome.dom.wustl.edu</a>/</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br />
<b>Q: What is Wolfram syndrome?</b></span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><b><br /></b>
A: Wolfram syndrome is a genetic form of diabetes mellitus. In addition to diabetes mellitus, most patients suffer from optic nerve atrophy and neurodegeneration, especially brain stem and cerebellar atrophy.</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br />
<b>Q: What is diabetes mellitus?</b></span><br />
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A: Diabetes mellitus is a group of disorders characterized by hyperglycemia (high blood sugar levels). This is due to either an absolute deficiency of insulin, as occurs in type 1 diabetes and Wolfram syndrome, or a relative deficiency of insulin, as occurs in type 2 diabetes.</span><br />
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<b>Q: What is diabetes insipidus?</b></span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br />A: Diabetes insipidus is one of the common symptoms in patients with Wolfram syndrome. It is defined as the passage of large volumes of dilute urine. It has the 2 major forms, and patients with Wolfram have the central diabetes insipidus.</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br />1. Central (neurogenic, pituitary, or neurohypophyseal): characterized by decreased secretion of antidiuretic hormone called vasopressin.</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;">2. Nephrogenic: characterized by decreased ability to concentrate urine because of resistance to vasopressin action in the kidney.</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br /><b>Q: What is optic atrophy? Is it different from retinopathy? Is there any treatment?</b></span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br />A: The mechanisms of vision impairment in Wolfram syndrome and type 1 diabetes are different. In short, the vision impairment in type 1 diabetes is a problem in small blood vessels supplying nutrition to the eyes. It is caused by high blood sugar levels and called retinopathy.</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br />The vision impairment in Wolfram syndrome is a problem in neuronal cells in the eyes transferring the electrical signal produced in the eye to the brain. It is caused by neuronal cell death and called optic atrophy.</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br />There is currently no treatment for optic atrophy. One of the major neuronal cells in the eyes declining in Wolfram syndrome are “retinal ganglion cells” which transmit electrical signals to the brain. If we can make these cells and transplant them to Wolfram patients, we can possibly treat blindness or improve eyesight. To accomplish this, we need a source for new retinal ganglion cells. I believe that induced pluripotent stem cells (iPSCs) is the source for the new retinal ganglion cells.</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br /><b>Q: “Is there any relationship between diabetes and optic nerve atrophy?”</b></span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br />A: This question implies a few different things. Here are my answers. </span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;">1. Type 1 Diabetes</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;">I believe that there is no direct relationship between type 1 diabetes and optic atrophy. Type 1 diabetes is an autoimmune disease. Our immune cells attack antigens highly expressed in pancreatic β cells in type 1 diabetes. These autoimmune cells usually do not attack optic nerve although patients with type 1 diabetes are susceptible to other autoimmune diseases. As I mentioned in my previous blog, patients with type 1 diabetes may develop retinopathy if there blood sugar levels are not properly controlled.</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br />2. Wolfram syndrome</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;">In Wolfram syndrome, there is probably a direct relationship between diabetes and optic nerve atrophy. Both pancreatic β cells and optic nerve are susceptible to endoplasmic reticulum dysfunction. So β cell death and death of retinal ganglion cells have the same etiology, i.e. ER dysfunction.</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br />3. Do all patients with Wolfram syndrome have diabetes and optic nerve atrophy?</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br /></span><span style="font-family: Times, Times New Roman, serif; font-size: large;">The answer is, “No.” In most cases, diabetes is the first manifestation of Wolfram syndrome, followed by optic atrophy. However, there are some patients who develop optic atrophy first and don’t develop diabetes for a long period of time. I know one patient with Wolfram whose diabetes was diagnosed at 40 years old. I don’t know why, but it seems like these patients tend to have milder symptoms. I am very interested in carefully studying these patients because I may be able to find a way to delay the progression of Wolfram through these patients. This effort is underway (i.e., modifying my human study protocol).</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br /><b>Q: What can you do to improve "neurogenic bladder" ?</b></span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br />A: Many patients with Wolfram syndrome experience neurogenic bladder. I always recommend that a patient consult with a urologist if he/she has a problem in urination. Here are my thoughts.</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br />1. What is neurogenic bladder?</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;">Our urination is regulated by two types of muscles in the bladder. These are the detrusor muscle and sphincter muscle. When we urinate, the detrusor muscle pushes out the urine and the sphincter muscle relaxes to open up the way out. These muscles are controlled by a part of the brain and neuronal cells connected to the bladder. Neurogenic bladder is a term applied to dysfunction of the bladder due to dysfunction of a part of brain and neuronal cells. In short, this is a problem in neuronal cells.</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br />2. What can you do?</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;">I always recommend that a patient see a urologist to determine the status of neurogenic bladder and get advice.</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br />3. Our progress</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br /></span><span style="font-family: Times, Times New Roman, serif; font-size: large;">As I mentioned in my previous blog, our recent progress strongly suggests that neuronal cell dysfunction in Wolfram syndrome is caused by dysregulation of cellular calcium homeostasis. We are developing a treatment to manipulate the calcium homeostasis in patients' cells using a drug, and making significant progress. I hope that my strategy will work out.</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br /></span><span style="font-family: Times, Times New Roman, serif; font-size: large;"><br /></span><b><span style="font-family: Times, Times New Roman, serif; font-size: large;">Q: What are electrolytes and sodium? </span></b><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br />A: Electrolytes are "salts" in our blood and cellular fluids. The difference between the concentrations of these salts inside and outside the cells regulates the contraction of muscle cells and the signal transduction in brain cells (neurons). Sodium is the major salt outside the cells. The reference range for serum sodium is 135-145 mmol/L.</span><br />
<span style="font-family: Times, Times New Roman, serif; font-size: large;"><br />It seems like some patients with Wolfram syndrome experience "low sodium." Our body regulates sodium levels by balancing water in the body with use of antidiuretic hormone. DDAVP is often prescribed for patients with Wolfram syndrome because they tend to produce less antidiuretic hormone and produce excess amount of urine. DDAVP is a synthetic antidiuretic hormone, regulates the body's retention of water, and decreases the volume of urine. The challenge for Wolfram patients is that they tend to have bladder problems and may need to go to bathroom often. This is not because of the excess production of urine, but they may increase the dose of DDAVP, which increases the body's retention of water and may lead to low sodium levels. As our colleague Dr. Marshall recommends, Wolfram patients should consult with their endocrinologists if they feel their serum sodium levels are low.</span><br />
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In addition, serum sodium levels may not be reliable when patients have poor renal functions or have severe hyperglycemia.</span>Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-11048445834223988862014-10-30T06:45:00.003-05:002014-10-30T06:46:47.199-05:00Are genetically engineered cells safe?<span style="font-size: large;">I see great potential in stem cell-based therapies, especially induced pluripotent stem cells (iPS cells) derived from patients' skin cells. At the same time, I am aware of challenges we may face. One of the major issues is safety. Because stem cells can differentiate into any types of cells, there is a chance that these cells become tumors. So we should make sure that we terminally differentiate them into specific types of cells. In addition, we should frequently monitor transplanted cells. That's one of the reasons I am interested in transplanting stem cell-derived eye cells. Eye is probably the only place in our body where we can easily and frequently monitor the status of transplanted cells.</span><br />
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<span style="font-size: large;">Thank you for reading today's blog. I hope you have a wonderful day. Cordially, Fumi Urano</span><br />
<span style="font-size: large;"><a href="http://wolframsyndrome.dom.wustl.edu/">http://wolframsyndrome.dom.wustl.edu/</a></span>Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-73245629548101153922014-10-29T07:43:00.001-05:002014-10-29T07:49:31.582-05:00Raise Awareness October 29, 2014<span style="font-size: large;">It is important for us to raise awareness of Wolfram syndrome and other rare diseases. I often talk about this topic because this is so important. We need more doctors who know about Wolfram syndrome in <a href="http://wolframsyndrome.dom.wustl.edu/physicians-who-see-patients-with-wolfram-syndrome/" target="_blank">each state</a> or city. We need to develop new treatments for the disease and bring them to patients as soon as we can. We are racing against time and every moment counts. We need to develop stem cell-based therapy for the disease and bring this to the clinic swiftly. All of these are required to accomplish a cure and can be accelerated by raising awareness. We will keep on working with you. Please help us spread the word. </span><br />
<span style="font-size: large;"><a href="http://wolframsyndrome.dom.wustl.edu/">http://wolframsyndrome.dom.wustl.edu/</a></span><br />
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<span style="font-size: large;">Thank you for reading this blog. I hope you have a wonderful day. Kindly, Fumi Urano</span>Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-19461815653232655922014-10-28T07:25:00.002-05:002014-10-28T07:27:16.044-05:00Combating optic nerve degeneration in Wolfram syndrome<span style="font-size: large;">One of the most important developments in my team is our collaboration with <a href="http://wuphysicians.wustl.edu/physician2.aspx?PhysNum=3136" target="_blank">Dr. Raj Apte's</a> team. Dr. Apte is a renowned physician-scientist and expert in retinal surgeries and molecular biology. His and our teams are working together to make new mouse models of Wolfram syndrome to study the mechanisms of optic nerve degeneration and create different types of eye cells using iPS cells of patients with Wolfram syndrome. I will keep you updated about our progress.</span><br />
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<span style="font-size: large;">Thank you for reading this blog. I hope you have a wonderful day. Kindly, Fumi Urano</span>Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-54694927289736962552014-10-27T19:42:00.002-05:002014-10-27T19:42:25.769-05:00Wolfram syndrome website at Washington University Medical Center<span style="font-size: large;">I hope you help us spread the word to raise awareness of Wolfram syndrome, the most difficult form of diabetes. <a href="http://wolframsyndrome.dom.wustl.edu/">http://wolframsyndrome.dom.wustl.edu/</a></span><br />
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<span style="font-size: large;">Kindest regards,</span><br />
<span style="font-size: large;">Fumi Urano</span>Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-21291081102216272582014-10-27T07:13:00.000-05:002014-10-27T07:13:29.013-05:00Stem cell-based therapies Q&A-Fate of transplanted cells<span style="font-size: large;">I received an intelligent and important question yesterday.</span><br />
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<span style="font-size: large;">Q: iPS cell-derived insulin-producing cells may be attacked again by autoimmune cells in Type 1 diabetes. iPS cell-derived insulin-producing cells and eye cells may degenerate again in Wolfram syndrome. What is the solution?</span><br />
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<span style="font-size: large;">A: This is a very important question. Before we transplant iPS cell-derived cells, <b>we need to modify disease-causing gene structure in Type 1 diabetes and Wolfram syndrome.</b> In Type 1 diabetes, we probably need to modify insulin gene structure. In Wolfram syndrome, we need to modify Wolfram gene structure. This can be accomplished by genome editing. The genome editing technology is a new type of gene therapy. Using an enzyme and artificially designed guide RNA, we can modify gene structure. We are actively working on this.</span><br />
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<span style="font-size: large;">Thank you for reading this blog. I hope you have wonderful Monday. Take care, Fumi Urano</span>Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-89392263705201977352014-10-26T08:12:00.001-05:002014-10-26T08:14:41.240-05:00Stem cell-based therapies - How long?<span style="font-size: large;">Here is another question related to stem cell-based therapies. </span><br />
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<span style="font-size: large;">Q: How long will it take for stem cell-based therapies to become mainstream? </span><br />
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<span style="font-size: large;">A: There are multiple ongoing clinical trials based on stem cell-based therapies. I feel that the development of workflows for manufacturing and quality control is one of the key issues. Regulators (such as FDA), researchers, clinicians, and manufactures should work together to solve this issue. </span><br />
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<span style="font-size: large;">Thank you for reading this blog. Enjoy wonderful Sunday. Fondly, Fumi Urano</span>Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-34748085848365039252014-10-25T07:12:00.003-05:002014-10-25T07:14:04.443-05:00Stem cell-based therapy Q&A - Medical Use<span style="font-size: large;">Here is another question I often get.</span><br />
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<span style="font-size: large;">Q: How can we use stem cells for the treatment of Wolfram syndrome and Type 1 diabetes.</span><br />
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<span style="font-size: large;">A: Stem calls can differentiate into specific cell types including insulin-producing cells, retinal cells, and brain cells. The most important function of stem cells, especially induced pluripotent stem cells (iPS cells), is their potential use as "cell-based therapies." iPS cells are a type of stem cells derived from patients' own skin cells and could be used to repair damaged tissues. </span><br />
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<span style="font-size: large;">For patients with Type 1 diabetes, iPS cells could be prompted to differentiate into insulin-producing cells and transplanted into the body. <b>The body wouldn't reject these new cells</b> as they would with donated cells or tissues from other individuals (called immune rejection). </span><br />
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<span style="font-size: large;">For patients with Wolfram syndrome, iPS cells could be stimulated to differentiate into insulin-producing cells, eye cells, and brain cells and transplanted into the body. Insulin-producing cells could be transplanted under the skin. We need to find the best way to transplant eye cells and brain cells, and the research is ongoing to figure this out.</span><br />
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<span style="font-size: large;">Thank you for reading this blog. I hope you have a wonderful weekend. Kindly, Fumi Urano</span>Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.comtag:blogger.com,1999:blog-2227548899152332383.post-46365781442147440742014-10-24T07:38:00.002-05:002014-10-24T07:39:35.167-05:00Wolfram syndrome UK<span style="font-size: large;"><a href="http://www.wolframsyndrome.co.uk/index.html" target="_blank">Wolfram syndrome UK</a> is a support group for patients with Wolfram syndrome in the UK. Mrs. Tracy Lynch is leading this initiative and has been helping us spread the word in the UK. They are partnering with <a href="http://www.birmingham.ac.uk/staff/profiles/cem/RGD/barrett-timothy.aspx" target="_blank">Dr. Barrett</a>, a pioneer in Wolfram syndrome research. I respect and appreciate their efforts. Thank you, Thank you, Thank you.</span><br />
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<span style="font-size: large;">I will visit the University of Birmingham Medical Center where Dr. Barrett holds the endowed professorship and is a staff physician soon to discuss our next steps. I will also meet with Mrs. Lynch and patients with Wolfram syndrome in the UK. It is always my privilege to work for patients with Wolfram syndrome.</span><br />
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<span style="font-size: large;">Thank you for reading this blog. I hope you will have a wonderful weekend. I am grateful and hopeful. Kindly, Fumi Urano</span>Anonymoushttp://www.blogger.com/profile/14327584805115981357noreply@blogger.com