We went to Children’s Hospital today and Raquel was more excited this time than previous visits.
She was getting her Omni Pod (Insulin Pump). Her blood sugars have been all over the place, which is not a good thing. When her sugars are high or low they can affect her vision, moods and appetite. Did I mention, MOODS? This little girl is one of the sweetest kids, but let me tell you, if she is really high or really low, her head will spin and green foam will come out of her mouth.
Putting on the Omni Pod was a bit tricky at first and a little scary for us all. With the apprehension also comes a bit of relief because Raquel’s blood sugars should become more stable. For Raquel, she is the most excited because she can start to spend the night at some of her friends houses now. Before she would have to get insulin shots at dinner and right before bed, not to many parents are keen on having to give insulin shots. It is the little things in life that we all take for granted, like sleepovers. These are the little things that really make Raquel happy.
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 Foundation2015-01-27 01:43:042020-09-07 20:10:35It’s the Little Things
(Left to Right): My nephew Shane Snow, my son Jack and my nephew Jake Peters
Since my nephew’s diagnosis of Neuromyelitis Optica (NMO) I was curious if there were any foundations representing NMO, after all, this is a rare disease just like Wolfram syndrome.
My sister sent me a link to a foundation called Guthy-Jackson Foundation. When I read about this foundation, I was a little envious of what they had accomplished in six years. They have started clinical trials, have a beautiful website, patient days and even a book written by the mother and daughter who has NMO. My initial reaction was relief for my nephew; there was network out there and in LA of all places where he lives. On the other hand, I was envious. Guthy, yes the famous Guthy-Renker infomercial founder and Jackson, the Victoria Jackson makeup line and infomercial guru are the parents of the child who was diagnosed with this disease. This power couple has an open checkbook to make what needed to happen, happen. People have to understand that in order to discover a drug to stop the progression of a disease and to find a cure, science and research has to take place and that takes millions and millions of dollars. What upsets this “mom on a mission” is that these patients are suffering and dying because of a lack of funding. My goal for 2015 is to find the right donors that can help us get this job done. It will happen, mark my words…IT WILL HAPPEN.
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 Foundation2015-01-12 20:27:572020-09-07 20:10:35We Can Be Like The Big Foundations
I am writing this from an airplane on my way home from Southern California after visiting my nephew, Jake, who has been lying motionless in a hospital bed for the last 16 days.
Jake is an unbelievable 17-year old, great baseball player, as well as a type 1 diabetic. He has had diabetes since he was 20 months old. He could not breath the afternoon of December 15th and told his dad he was loosing sensation in his feet. He later collapsed and has been on a ventilator and unable to move his arms and legs since. He was diagnosed with an autoimmune disease called Neuromyelitis Optica (NMO). NMO is a rare relapsing autoimmune disorder that causes inflammation in the optic nerve and spinal cord.
I went out to California to support my sister and to love on my nephew. Everyone thinks they have problems, I am the first to admit, especially watching my daughter struggle with her Wolfram syndrome. However, when you sit in a hospital room all day and watch your 17-year old nephew lie there limp, unable to move anything, we should all be thankful for the problems we have because someone else always has it worse.
It broke my heart because three of his best friends and teammates came over to see him after baseball practice and they all asked him how he was doing. He mouthed, “I can’t move.” He should be the one in that uniform worrying about baseball, what he is going to do on Friday night, homework, etc., not wondering if he is ever going to walk again, use his arms or breath on his own. But for now, all we can do is wait, hope and pray.
A Caring Bridge page has been set up for Jake Peters where you can follow along with his story and progress. We welcome any prayers, thoughts and get well wishes for Jake. Thank you!
Last summer, we had a successful research clinic, with 24 patients and their families attending from all over the world and the US. We welcomed three new patients to our group this year and in a whirlwind 4 days, we performed 22 MRI scans and over 350 individual appointments!
Since then, we have identified additional patients that are good candidates for this study or who are interested in a clinical consultation (or both). Rather than waiting until next summer to collect the research data, we have started to bring these families in to WU one at a time. We call this a ‘mini-clinic’. Each patient undergoes the same tests with our usual wolfram research clinic doctors and investigators, staying overnight in St. Louis. So far, we have done this with 2 families, and 2 more are being scheduled. The mini-clinic has been working quite well and is a nice option for families that can’t or don’t want to travel to St. Louis in July. It also helps us get more data at a quicker pace, which is in the best interests of everyone.
We have also seen four new patients for clinical consultations and for diagnosis of Wolfram. We are always happy to consult with patients or their physicians about whether they might have Wolfram and how to obtain testing. We can also arrange for them to have care by any of our team who has experience with Wolfram.
Thank you to all of the families for participating in all of our research, and to all of our colleagues and staff who help make the big research clinic and our new mini-clinics happen so smoothly.
Tamara Hershey, Ph.D. Professor
Psychiatry, Neurology and Radiology
Washington University School of Medicine
Scientific Director of Clinic and PI, NIH R01 “Tracking Neurodegeneration in Early Wolfram Syndrome”
Bess Marshall, M.D.
Professor
Pediatrics
Washington University School of Medicine
Medical Director of Clinic
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 Foundation2014-11-19 21:50:572020-09-07 20:10:35The “Mini-Clinic”: News from the Wolfram Research Clinic at Washington University
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.
Dr. Fumihiko Urano
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.
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.
Thank you for reading this. I would like to send kind thoughts toward you. I would like you to stay optimistic. Thank you again.
Q: How can we use stem cells for the treatment of Wolfram syndrome and Type 1 diabetes.
A: Stem cells 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. For patients with Type 1 diabetes, iPS cells could be prompted to differentiate into insulin-producing cells and transplanted into the body. The body wouldn’t reject these new cells as they would with donated cells or tissues from other individuals (called immune rejection). 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.
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?
A: This is a very important question. Before we transplant iPS cell-derived cells, we need to modify disease-causing gene structure in Type 1 diabetes and Wolfram syndrome. 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.
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 Urano2014-10-27 13:50:452020-09-07 20:10:36Stem cell-based therapy Q & A – Medical Use
I receive many questions related to Wolfram syndrome and other medical conditions. Here are some of them. Please feel free to contact me if you have any questions.
Dr. Fumihiko Urano
Q: What is diabetes insipidus?
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.
1. Central (neurogenic, pituitary, or neurohypophyseal): characterized by decreased secretion of antidiuretic hormone called vasopressin.
2. Nephrogenic: characterized by decreased ability to concentrate urine because of resistance to vasopressin action in the kidney.
Q: What is optic atrophy? Is it different from retinopathy? Is there any treatment?
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.
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.
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.
Q: “Is there any relationship between diabetes and optic nerve atrophy?”
A: This question implies a few different things. Here are my answers.
1. Type 1 Diabetes
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.
2. Wolfram syndrome
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.
3. Do all patients with Wolfram syndrome have diabetes and optic nerve atrophy?
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).
Q: What can you do to improve “neurogenic bladder”?
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.
1. What is neurogenic bladder?
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.
2. What can you do?
I always recommend that a patient see a urologist to determine the status of neurogenic bladder and get advice.
3. Our progress
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.
Q: What are electrolytes and sodium?
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.
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.
In addition, serum sodium levels may not be reliable when patients have poor renal functions or have severe hyperglycemia.
Barclay and I are moving forward! As parents you want to do everything possible to provide the best life for your children.
Easier said than done when one of them has a life threatening disease. If you pray hard enough for the strength to just move forward, somehow, the good Lord will provide!
This past weekend Barclay took Raquel to Best Buy and bought her a TV for her bedroom. He mounted it on the wall next to her bed and with it’s swinging arm, she can move it right in front of her face. It has been at least nine months since she has watched TV. After her dad installed it, her eyes light up and she was so excited to sit and enjoy the TV like everyone else. She just wants to be like everyone else.
This week I had a meeting at school with about 12 other individuals from Raquel’s school to discuss her progress. It was a bit overwhelming to walk into a conference room and see all these people sitting around a huge conference table to discuss the needs of you child. I am very grateful that Raquel attends such a great school district and I am even more grateful that Barclay and I are accepting the fact that Raquel has special needs. Her needs keep us fighting; fighting for change, and fighting for a CURE!
Last Friday, I had an unbelievable discussion with the owner of a company that has offered their help to The Snow Foundation to expand our wings.
Stephanie Snow Gebel
At the end of the meeting, I remember walking out of his office completely perplexed. I felt like I had just had a discussion with God, my mom, my dad, a priest, my best friend, my husband; the list goes on and on. I felt deflated, yet uplifted. Honestly, I really didn’t know how to digest what I had just heard. He really made me think about my life in ways that I never had before.
Now, here I am five days later. I got the kids off to school, cleaned up the house, did a few bills and answered a few emails. Then, I climbed back into bed and put the sheets over my head and cried. I felt depressed and overwhelmed with LIFE. I have many questions that I want answered. I want to know WHY certain things happened. Growing up, I always wanted to know WHY. (Just ask my sister and brother. Our family dinner discussions would last an hour longer than needed because I would go head to head with my dad on wanting to know why. I had many bruised legs from J.T. kicking me under the table, because he wanted me to shut up and let it be…). My personal world, my business world and my SAVE the Wolfram World completely overwhelm me at times. I thought, maybe mentally I am not strong enough to handle all of this. I laid in bed feeling sorry for myself and prayed to God for continued strength, especially strength of the mind. The mind is so powerful and it can take you places that you really don’t want to go. Unfortunately, I have been to a couple of places that I do not wish to re-visit. Still under the covers and crying and being pissed off, a thought came to mind. I believe this came from the man upstairs. It was time to grab my phone and listen to Oprah and Deepak Chopra’s meditation message of the day.
A couple weeks ago, the Foundation’s Executive Director and I had challenged each other to a 21-day meditation with Deepak and Oprah. It’s been tough because we both have four children, run the foundation and much much more, but we decided to give it a try. When we actually keep our minds from wandering, it’s been great! Today’s message was on GRATITUDE.
“There is a deeper kind of gratitude that goes beyond our conceptions and beliefs of good and bad. This expanded sense of gratitude rejoices in life exactly as it is, right now….life is perfect in spite of its imperfections. Our heart is big enough to embrace and appreciate life as a whole, just as it is, without worrying about whether it is good or bad.”
It was great to hear that Oprah has her moments of self doubt, just like me. Oprah has taught herself to let these emotions pass and she continues to remind herself that she is “thankful for all that she has TODAY.” I need to try and train my mind to be thankful for all that I have and know that bad things happen to good people and I may never know why. As I continue to grow day to day, I am trying to teach myself that I don’t need to know WHY everything happens. When life hands you lemons, you need to make lemonade…sometimes the lemonade is mediocre other times the lemonade is outstanding, it doesn’t really matter does it, as long as you still make it!
I was watching the video that our friend and patient, Alejandro, was doing an ice bucket challenge.
Dr. Fumihiko Urano
This project originally started for ALS. So I was checking the ALS-related websites and found the following youtube video. As most of you know, ALS (amyotrophic lateral sclerosis) is a neurodegenerative disease, leading to the progressive degeneration of the motor neurons. As a result, patients with ALS may become totally paralyzed.
In these video series, many friends of Mr. Hiro Fujita, who has lost his voice due to ALS, read his messages. The project is called “END ALS.” He was in the advertising business. So many celebrities read his messages. One of his messages was toward his mother. I would probably say the same word. There is an English caption in each video. He said, “Mom, Thank you.”
He has a website, END ALS. He often uses the word, “HOPE.” What do we need to help our patients suffering from life-threatening diseases? How can we create HOPE? Let’s think about the basics.
1. Make correct diagnosis and refer them to the best specialists.
2. Develop therapeutics to stop the progression.
3. Replace damaged tissues.
These three should happen simultaneously. We need all of these. I want to END WOLFRAM, END DIABETES, END ALS, and…
I hope you will have a wonderful day. Thank you for reading this blog. Thank you for your supports. Thank you, thank you, thank you.
Thank you again, and Regenerate to Beat Degeneration.
Posted: 01 Sep 2014 05:53 AM PDT
I was surprised and glad to see that our patient and friend, Alejandro, was doing an ice bucket challenge for Wolfram syndrome. Thank you again, Ale and the team Alejandro!
I often get questions about “regenerative medicine.” I really like the following video created by the Mayo Clinic. “Regenerate” is the opposite of “degenerate.” Because Wolfram syndrome is a degenerative disease, the best way to counteract is to “regenerate” damaged tissues.
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 Urano2014-09-01 22:18:212020-09-07 20:10:36END WOLFRAM, END DIABETES, END ALS
We went to Children’s Hospital today and Raquel was more excited this time than previous visits.
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