Strange Truth – Adam Zwan

Photo of Adam Zwan

Adam Zwan

Do you live a risky life or do you fly straight and narrow? After being diagnosed with Wolfram Syndrome I began paying close attention to my surroundings and the lives of others. Strangely, it became clear that individuals who live life without taking chances or making risky decisions end up with the dull side of the blade. Unfortunately for people who avoid trouble and mischief, consequences are paid with permanent life changes. On the other hand, those who live on the edge seem to have a little more fun in their lifetime; these individuals may be faced with consequences but the price is paid and the risky lifestyle is continued.
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Chores Anyone? – Lauren Gibilisco

Photo of Lauren GibiliscoAs you know, living with Wolfram syndrome poses many challenges for me, including doing my chores.  With my vision impaired, I’ve had to come up with different ways of doing things and I thought I’d share them with you.

I start with making my bed.  My bedspread has two raised rope designs going vertical.  This lets me know how far to pull it on each side so it is even.

Almost every day I empty the dishwasher.  I know how the dishes feel so I know where to put them.  How large the bowl is lets me also know where it belongs.  Every dish has a certain spot in our cabinets so I know exactly where they go.  I run my hands over the spokes in the dishwasher to make sure I have gotten everything out.  Since I know where the dishes are I know how to set the table.  The only thing I have trouble with is the salt and pepper shakers but we put a braille strip on each item so I know what it is.

They do not let me clear the table.  I have broken too many dishes slamming them on top of each other.  Or I run into them when they are coming through.   I am also able to get things out of the refrigerator because again everything has a certain place to go.  Although sometimes my dad doesn’t put it back where it should go. One day when we were having hotdogs for lunch my dad said “why is there chocolate syrup on the table?”  I thought it was mustard.  Good thing he saw it before I put it on my hotdog.  That would not have been good.  My mom doesn’t like me cooking on the stove while she isn’t there.  She said she doesn’t want to come home from a long day at work and find the fire dept there.

I also dust and vacuum both the upstairs and the downstairs.  I’m not sure I get everthing wiped off or picked up but I just try to keep going in a straight line hoping I am going in the right direction.  I also sweep the kitchen and bathroom floors.  I sweep hopefully into a pile and bend down and pick it up with the dustpan. I listen to see how much is coming out of the dustpan so I know how much is still being picked up.  I can’t see what I am doing so I just do it several times until I think everything is gone.  I also use my bare feet to walk around and feel if I missed anything.

I am in charge of doing the family wash.  I know what my dad’s shirts feel like with all the buttons.  I also know the weight and feel of his white tee-shirts so I am able to separate the whites from the darks.  Of course I am able to tell the difference between a top and pants so I know which to hang and which to fold.  My mom also buys the pod detergents so I don’t have to worry about measuring everything or knowing where to pour.  I am also able to put the washer and dryer on the right settings because we use stick on raised dots.  These go on the start buttons and the temperature settings so I know how to adjust for the different types of clothes.

The buttons are also used on the stove and microwave.  It is digital so I have the dots put on the one, the three and the five buttons so I know the correct temperatures or time settings.  Now getting food out of the oven is a little bit harder.  You don’t want to go feeling around too much in a hot oven looking for the pan.  My mom bought the silicon gloves that go up to my elbows.  You cannot get burned with these on.  So I feel confident reaching in the oven.  They also wipe off cleanly or can be put in the dishwasher if anything spills on them.

I spend a lot of time at home alone.  My parents also work very hard and long hours.  Doing all these chores makes me feel good that I am able to contribute to my family.  It also gives me something to do every day instead of just watching tv or listening to the radio.

So there you have it!  That’s how I do my chores while living with Wolfram syndrome.  Now I have to get back to work!

Lauren

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Patient Based Therapeutics – New Drug Candidates

New Drug Candidates

As I mentioned in my previous blogs, we have identified three FDA-approved drugs, one supplement, and new groups of drugs that can potentially delay the progression of Wolfram syndrome. We have been testing the efficacy of these drugs in cells from patients and two animal models of Wolfram syndrome. Preliminary data look good, and we have been working very hard to bring at least one drug to patients.

We have also identified a potential biomarker that would be useful for monitoring the efficacy of our new treatment. I would like to thank patients who donated blood samples to us. Recently, some families donated blood samples from patients’ siblings, and these samples were really helpful to confirm our findings.

I have been trying to establish firm relationships with biotech companies and nonprofit organizations to bring these drugs to our patients through clinical trials. Our lawyers have been helping us a lot. I will keep on pushing the envelope with my wonderful team and colleagues.

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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What is Taekwondo to Me? – Adam Zwan

As a Wolfram Syndrome patient, I have learned that controlling my diabetes and my overall health can slow Adam Zwan doing Taikwando.down the progression of any illness.  Thus, I have become a huge advocate for fitness and nutrition as a means of promoting quality years of life.  Health is a broad term that encompasses physical, mental, psychological, intellectual, and spiritual health.
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Patient-Based Therapeutics Part 6

Wolfram Syndrome iPS Cells Progress

I received many emails regarding our progress on Wolfram syndrome induced pluripotent stem cells (iPS cells) in the past two weeks. I would like to update you on a few things. As I mentioned in my previous blogs, we have created many iPS cells from skin cells of patients with Wolfram syndrome. These iPS cells can differentiate into various types of cells including brain cells and pancreatic beta cells that are damaged in patients with Wolfram syndrome

1. Disease modeling 
We could successfully differentiate these iPS cells into neural progenitor cells. These are immature brain cells. We found that neural progenitor cells from patients are not completely damaged, which was surprising, but good news to us. Instead, they have altered calcium homeostasis. My impression right now is that cells from patients with Wolfram syndrome are “sensitive” to environmental stress, especially stimulus that changes cellular calcium levels. So we are looking for drugs that can modulate calcium homeostasis in cells to develop a treatment for Wolfram syndrome.

2. Testing drugs
As I mentioned above, we are focusing on drugs that can modulate calcium homeostasis in cells, especially endoplasmic reticulum calcium levels, to develop a treatment. Three drugs out of five candidate drugs that we have identified so far can control endoplasmic reticulum calcium levels. We are testing these three drugs using iPS cells.

3. Correcting a mutation
Using a special enzyme and artificial DNA, we are replacing an abnormal segment of Wolfram gene with a normal segment of Wolfram gene in patient-derived iPS cells. In theory, we should be able to correct altered calcium homeostasis through this process.

4. Making eye cells
A group in Columbia University Medical Center in New York could successfully make pancreatic beta cells from Wolfram syndrome iPS cells. We are collaborating with this group. So we are focusing our own efforts on making eye cells from Wolfram syndrome iPS cells. This is a collaboration project with a group in a major medical center in Japan. They have a special “recipe” for making eye cells. Because a clinical trial using this technology for an eye disease will start in a few weeks in Japan, I feel that this collaboration is so important for us. A physician and scientist who is working on this collaboration project will come to the US and work with us in a few months. The arrangement has been made, and the Japanese agency will partially support this effort.

You may be interested in a clinical study using iPS cells for an eye disease. Here is some info.
http://blogs.nature.com/news/2013/07/japan-to-start-stem-cell-study-on-humans.html
http://www.riken.jp/en/pr/press/2013/20130730_1/

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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St. Patrick’s Day – Lauren Gibilisco

Lauren GibiliscoHello Everyone,

The last few weeks have been fun and entertaining.  It started out on St. Patrick’s Day.

I am 75% Irish and our family has always celebrated it.  When I went to work on St. Patrick’s Day I was dressed as a leprechaun.  My clothing was green and I wore a green hat. I had shamrock on my face and of course I had the height of a leprechaun because I am a wee bit short.  I have a pretty good Irish accent and I went around saying “top of the morning to ya.”

After that I went back with my mom to the grocery store.  I became the leprechaun greeter.  The customers all loved me sharing my heritage with them.

Then last week I went to the endocrinologist.  The resident asked me questions and took my information down.  She said she would discuss my health with the doctor.  The door opened seconds later and I expected to see the doctor.  But it was the nurse who came in.  She asked me if I had my machine and if I would test my blood sugar.  I said I had just checked it before coming in here and I was fine.  She said to check it anyway.  Then my mom asked “why do they think she is low?”  The nurse said that the resident thought I was talking too much and too fast and might have a low blood sugar.  I checked my blood sugar and it was fine.  The nurse said “as soon as I saw you I knew that wasn’t the case.”  She said “that’s just typical Lauren.” LOL

I went out to dinner with a couple of friends.  One of them had just gotten engaged.  She said it was going to be a small wedding and she had to limit the invitations, but she said I made the cut.  A couple of days later I received a phone call from two of my friends who are in college.  I hadn’t heard from them in over a year so it was a pleasant surprise.  They came over to my house and we just talked and got caught up on our lives and watched a movie.

This last weekend I went up to Omaha to see my cousin who was in a musical at college.  The musical was the Phantom of the Opera.  I had seen the Broadway show in New York City about nine years ago.  At that time I could still see.  So even though I was not able to see the characters on stage I knew from the music what was going on.  All my aunts came down to see the musical so I was able to spend time with them and my grandparents.  It is always nice sharing memories and laughs.

The last few weeks have been busy and fun.  It was great seeing old friends, new friends and relatives.  Every time we get together we create a lasting memory.

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Patience – Adam Zwan

Photo of Adam ZwanAll great things are worth waiting for. Being patient has proven to be one of my greatest attributes and has served me well throughout life.  No matter the task, managing time wisely and being patient has given me the ability to start things, do them well, and finish with satisfaction.
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Wolfram Syndrome iPS Cells: The First Human Cell Model of Endoplasmic Reticulum Disease

Publication: American Diabetes Association | Publication Date: March 2014

Authors: Fumihiko Urano

Wolfram syndrome is a rare autosomal recessive genetic disorder with clinical signs apparent in early childhood. This condition is characterized by childhood-onset diabetes, optic nerve atrophy, deafness, diabetes insipidus, and neurodegeneration, and it results in death in middle adulthood (1–3). Genetic and experimental evidence strongly suggest that endoplasmic reticulum (ER) dysfunction is a critical pathogenic component of Wolfram syndrome (4,5). However, there is a lack of complete understanding of the pathways and biomarkers involved in the disease process due to the limitations of animal models that do not accurately reflect human patients. As a result, despite the underlying importance of ER dysfunction in Wolfram syndrome, there are currently no therapies that target the ER, a deficiency that points to the urgent need to develop a human cell model of this condition. In this issue, Shang et al. (6) report that this has been successfully accomplished.

Read the entire publication article here.

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A Word From the Wolfram Study Group

Photo of Bess Marshall

Dr. Bess Marshall
(Photo courtesy of Robert J. Boston)

By Dr. Bess Marshall

All of the people working on the Wolfram studies at Washington University are grateful every day for the support of the Snow Foundation and all of the other groups that support our work.  The Washington University Wolfram Study group is continuing to work on analyzing the data that we have and to plan for collecting data that we still are lacking to come up with a reliable way to track progression of Wolfram Syndrome so that we will be prepared to be able to determine whether any intervention is helping.  Although we don’t yet have an intervention, we are hopeful that that day is not far off when we begin an intervention trial.  We are also accumulating as much information as we can to help provide recommendations for clinical care until that day arrives.  I am happy to provide letters to anyone with Wolfram who needs help with insurance, work, school, or disability issues, just contact me at marshall@kids.wustl.edu.

All the best to our good friends in the Wolfram community!

Dr. Marshall’s research interests have included intermediary carbohydrate metabolism, glucose transporter structure and function, and metabolic engineering to alter insulin resistance. She is currently funded by a National Institutes of Health Clinician-Investigator Development award, the Diabetes Research and Training Center, and is a scholar of the Child Health Research Center of Excellence in Developmental Biology at Washington University. Dr. Marshall’s clinical interests include all aspects of endocrinology and metabolism.

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Living With Wolfram Syndrome – Lauren Gibilisco

The Ups and Downs of Vision Loss

Photo of Lauren and Megan Gibilisco

Lauren and Megan Gibilisco

My week turned out to be quite eventful.  I am going to give you the ups and downs of vision loss.

It all started out when I knocked some sense into myself.  Inside the house I do not use my cane.  I went to go turn off the television and thought I was walking towards the light.  Unfortunately I didn’t see the wall in front of me and ran smack into it.  It knocked me right on my butt.  I went downstairs to show my mom my mouth.  I didn’t know but I had blood running down my face.  I had split my lip all the way back to the gum. My lower lip had teeth impressions where I bit down.   My upper lip was already starting to get a fat lip.  I am very fortunate that I did not knock out any teeth or break my nose.  So I had my mom take a picture and send it to my phone.  Three days later when I went to work I showed everyone my pictures.  They asked how did I do that.  My reply was I was standing outside and a large bird ran into me beak first.  I couldn’t believe that several people actually believed that.  My mom told everyone that I was fine because I am still able to talk.

My sister came home from Omaha for the weekend.  She brought her new puppy home for us to see.  She is a shorkie.  Her mom was a shih ti and her dad a yorkie.  Her name is Emmy.  This puppy is little.  She only weighs two pounds and will only grow to be five pounds.  I do not like animals much but I have grown fond of this puppy.  She loves to play and I love that I can play with her even though I can’t see her.  The only problem I have is that I worry about stepping on her.  She loves to run beside me when I leave a room.  So if she is going to be around me she will just have to learn not to walk in front of me.

My sister wanted to show off the puppy to her best friend. We drove to her house.  Luckily her brother came over to visit also.  Zach and I have been best friends since we were little.  He is getting married in July.  He wanted me to be a part of the wedding and asked me if I would like to be in charge of the guest book.  I asked him if I had to sign people’s names and he said no.  Zach said I would be like a greeter.  I think the job is perfect.  I just get to sit there looking lovely and greet people as they come in.  Perfect job for someone who likes to talk.

So for a week that I thought would be boring turned out to be quite exciting.  That just teaches you that losing your vision doesn’t mean your life will stop. So you never know what is going to jump in front of you….even if it’s a wall.


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