Chemical Chaperones Reduce ER Stress and Restore Glucose Homeostasis in a Mouse Model of Type 2 Diabetes

Publication: www.ncbi.nlm.nih.gov | Publication Date: February 4, 2016

Authors: Umut Özcan, Erkan Yilmaz, Lale Özcan, Masato Furuhashi, Eric Vaillancourt, Ross O. Smith, Cem Z. Görgün, and Gökhan S. Hotamisligil

Abstract

Endoplasmic reticulum (ER) stress is a key link between obesity, insulin resistance, and type 2 diabetes. Here, we provide evidence that this mechanistic link can be exploited for therapeutic purposes with orally active chemical chaperones. 4-Phenyl butyric acid and taurine-conjugated ursodeoxycholic acid alleviated ER stress in cells and whole animals. Treatment of obese and diabetic mice with these compounds resulted in normalization of hyperglycemia, restoration of systemic insulin sensitivity, resolution of fatty liver disease, and enhancement of insulin action in liver, muscle, and adipose tissues. Our results demonstrate that chemical chaperones enhance the adaptive capacity of the ER and act as potent antidiabetic modalities with potential application in the treatment of type 2 diabetes.

Read the entire publication article here.

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A Mom on a Mission!

prescription drug imageA quick description of my job; work 24/7, deal with scientists, researchers, doctors, philanthropists, sports figures, political figures, full time advocate for rare disease, counselor for parents and patients, breakfast, lunch, dinner meetings, travel around the world, public speaker, accountant, secretary, marketing and most important Fundraiser.

​​Combine all the above and they do not equal what it is like to fundraise. For anyone who has ever had to go out and ask for money, it is not fun. I hated it at first but now to be honest, I ​am learning to like it​. Because each morning that I wake up and see my beautiful 10 year old daughter Raquel slip farther and farther away from her independence, it ​makes me very mad​. Mad, because ​we are sitting around waiting. ​Our research is on hold, our clinical trials are on hold, drug therapies are on hold. The only thing holding us back is MONEY​. We need a minimum of $4M to do the necessary research on the eyes, ears, brain and bladder and begin clinical trials on drugs that could possibly stop the progression of this disease and may even restore vision.​ As per experts, as we get into trials we may need to adjust this amount, but we cannot wait till we have perfect knowledge. We need to act NOW to save our children. MONEY does make ​the world go round, without it, ​these patients​ do​n’t have a chance​.

​Please visit our ​crowdfunding campaign at Snowfunds.org. We are asking you to contribute and spread the word and support our humble cause. Thank you.

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Wolfram Syndrome: Diagnosis, Management, and Treatment

Publication: www.ncbi.nlm.nih.gov | Publication Date: January 7, 2016

Authors: Fumihiko Urano

Abstract

Wolfram syndrome is a rare genetic disorder characterized by juvenile-onset diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing loss, and neurodegeneration. Although there are currently no effective treatments that can delay or reverse the progression of Wolfram syndrome, the use of careful clinical monitoring and supportive care can help relieve the suffering of patients and improve their quality of life. The prognosis of this syndrome is currently poor, and many patients die prematurely with severe neurological disabilities, raising the urgency for developing novel treatments for Wolfram syndrome. In this article, we describe natural history and etiology, provide recommendations for diagnosis and clinical management, and introduce new treatments for Wolfram syndrome.

Read the entire publication article here.

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Wolfram Syndrome Support and Information Day in the UK

WSUK

The Snow Foundation was represented at the  3rd Annual Wolfram Syndrome Support and Information Day in the UK in November.   The conference had numerous speakers ranging from specialized service, therapeutics, developing treatments, urology, psychology and neurology, to name a few.  Dr. Fumihiko Urano gave a presentation on patient based therapeutics and Stephanie Snow Gebel spoke about The Snow Foundation to over 100 Wolfram patients and their families. It was an honor to represent the United States and our fight against Wolfram syndrome and diabetes. It was also refreshing to know that there are individuals who are fighting just as hard to better the lives of those who are living with this insidious disease. The Snow Foundation is looking into starting a similar workshop here in the States, although we are much larger than the UK, it will take a great deal of funding to implement such a program.

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Gianna’s Vision of Hope Fundraiser

Gianna Vision of Hope Photo

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2015 Wolfram Research Clinic Update

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Tenth High School Reunion – Lauren Gibilisco

It’s been 10 years since I graduated from High School. We had our 10th year reunion this last weekend. I had to find someone who could help lead me around. I love my mom but going to a reunion with your mom is just not cool, so I asked my friend Meredith to take me.

The first festivity was a float in a parade. The class reunions are always during our town’s celebration weekend. As much as I wanted to sit on the float with my classmates, I knew it would be impossible. The weather was 85 degrees which is way too hot for me to be outside long and then there was the problem of needing a restroom. We had to line up on our float an hour before the parade and then the parade was an hour long. I can’t go that long without needing the restroom. It really disappointed me but I’ve learned there are things I just can’t partake in.

The next festivity was out at a cabin.   I talked with my mom and decided it would just be too hard for me to walk across an uneven surface, be outside in the heat, and again needing the restroom. So we decided to just skip that also. Then my friend Meredith said she was only going to stay out there for an hour and would help guide me around. I was very excited about that. I really did want to go but didn’t want to be a burden to anyone. But Meredith insisted that I wouldn’t be a burden and she would be glad to take me there. I was really happy I went. I got to see a lot of my classmates. Well I couldn’t SEE them but I was able to talk with them and say hello. Meredith took me around and let me know who was there so I could say hello to everyone.

Then that evening there was a dinner banquet. Meredith again took me there and helped me to the table. Unfortunately not many of my classmates came. So I was really glad I was able to go to the cabin because I saw many more classmates then I would have been able to see at the banquet.

After the banquet everyone was heading to the bar to celebrate. There was a live band playing and it was less than ½ block to my house. Unfortunately by this time I was getting very tired. That darn fatigue was getting in the way of my continuing the celebration. I told everyone that I would be the designated driver to drive them home but no one took me up on that one. I wonder why? But overall it was a great experience and I’m glad I went and I’m glad that my friend Meredith took the time to help me enjoy the celebration. I am very grateful to her.

Image of Lauren Gibilisco's class reunion.

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Three Drug Targets. What is the difference?

We have identified three drug targets for Wolfram syndrome in the past two years. These are MANF, Calpain 2, and IRE1. What is the difference between these three molecules. Here is a short summary.

MANF: Enhances survival and proliferation of remaining cells.
Caplain 2: Activates cells death signal in Wolfram and Diabetes. So we need an inhibitor.
IRE1: Prevents the activation of cell death signals.
IRE1 and Calpain 2 are enzymes. So we need drugs that can control their activation levels.

MAFN is a secreted molecule. We can potentially use an artificial MANF (i.e., recombinant MANF) for treatment. Another pathway is to identify a receptor for MANF and develop a drug that can activate the MANF receptor.

Thank you for reading my blog. I always appreciate your encouragement. I think about our patients every day.

Take care,

Fumi Urano

Business man under the question mark

Business man under the question mark

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San Francisco Giants Recognize The Snow Foundation

Image of JT Snow and members of the Snow Foundation BoardOn Tuesday, July 7th at AT&T park, the San Francisco Giants celebrated “Snow Foundation Night” to raise awareness of its mission to find a cure for rare disease, Wolfram syndrome.  Prior to the 7:15 p.m. match up between the reigning World Series Champs and the New York Mets, former Giants first baseman and six time Gold Glove winner, J.T. Snow addressed the crowd on the important mission of the Snow Foundation.

Dr. Fumihiko Urano, Stephanie Gebel and Dr. Saad Naseer
Dr. Fumihiko Urano, Stephanie Gebel and Dr. Saad Naseer
Dr. Fumihiko Urano, Stephanie Gebel and Dr. Saad Naseer
Shane Snow and Stephanie Gebel
Shane Snow and Stephanie Gebel
JT Snow and members of the Snow Foundation
JT Snow and members of the Snow Foundation
JT and Shane Snow
JT and Shane Snow
Stephanie Gebel and Shane Snow
Stephanie Gebel and Shane Snow
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Vocational Rehabilitation – Adam Zwan

Maybe or Maybe Not

image of a golf cartOriginally, I was told that Vocational Rehabilitation could provide financial assistance towards a street legal golf cart. When I first heard these words I was exhilarated to think that independent transportation is a possibility. I am still not full time at the wellness and rehabilitation center I work for so financial assistance is needed to acquire a street legal golf cart. It was explained that I must obtain a quote for a golf cart, add it to my file, Vocational Rehabilitation would purchase the golf cart, and then Vocational Rehabilitation would receive a tax rebate. It was all planned out and I was feeling optimistic that a Wolfram Patient, like me, could increase level of independence. Although, I try my best to be cautiously optimistic by saying that it may happen or it may not.
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