Living With Wolfram Syndrome – Adam Zwan

Tired But Can’t Sleep

Image of sleeping manHave you ever experienced full body exhaustion but cannot fall asleep?  Fellow Wolfram syndrome patients may know exactly what I am talking about.  A snapshot of this sleepless exhaustion is lying in bed with a severe case of yawning while closing the eyes as tight as possible wishing for at least a few minutes of sleep. 

It has been suggested that I participate in a sleep study so that some solutions to restless nights of sleep can be developed.  However, part of my problem is not only the sleep patterns but the health issues I struggle with.  Due to Wolfram syndrome, I have to wake up each night to catheterize relieving discomfort, wake up every two hours to check my glucose, and try to relax a cold body that sometimes deals with shivering.  As always, it is not simply solved with one thing like sleep medication but bigger helping hands like an accurate continuous glucose monitor (CGM).  Something like a Dexcom CGM would relieve my body from having to wake up every two hours and relieve my alarm clock from mandatory overtime.  The only thing allowing me to continue daily routines is a 20 minute power nap every day.  It may be possible to obtain a Dexcom sensor in the future but until that day arrives I will continue going to bed each night eagerly awaiting the 5:00 A.M. alarm signaling that it is gym time.

Stem cell-based therapy Q & A – Medical Use

Here are two other questions I often get.

Q: How can we use stem cells for the treatment of Wolfram syndrome and Type 1 diabetes.

Image of iPS cellsA: 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.

Thank you for reading this blog.

Living With Wolfram Syndrome – Lauren Gibilisco

Photo of Lauren GibiliscoWell I managed to drive my mom nuts this week.  I have many items in my house that talk to me so I can function better.  But this week my watch stopped working. 

It was a talking watch.  Without it I have trouble knowing what time it is.  Time is important in our lives.  We need to know when to give shots or medicines. We need to know what time it is to eat or even what time it is to take a nap or go to bed. Our lives revolve around the clock.  So all throughout the day, I constantly asked my mom “what time is it?” It was a long week for her until my new watch arrived. 

When I went to my volunteer job this week I bumped into someone in an office.  It was someone else’s office so I didn’t know who it was.  That person said you still don’t have my voice memorized yet. She told me she was Barb.  When my parents owned their grocery store I had trouble always remembering voices especially because I have hearing loss.  I came up with an idea to always say hello and they would have a name made up that started with their first initial.  For example, Brianne would come up to me and say “hello Bambi.”  Well when I told Barb about that idea I told her to make up a word starting with “B”.  She said “I’m not going to call you that Lauren.” Everyone including myself burst out laughing.  I said “that didn’t occur to me.”  She said she would call me “beautiful” but I told her “brat” sounded more appropriate.  Going along with this theme, I was talking to a friend of my moms.  She asked if I was going to dress up for Halloween. I told her no.  She said “come on, you could dress like a princess and your mom could dress up like a witch.” I told her jokingly “she doesn’t need a costume for that.”

One of my mom’s friends hated thinking of me home alone in our house all the time.  I have no friends in this area.  So she decided that every other Friday she would come get me and we would go to lunch or dinner together.  She has known me since I was 5 years old.  I bet she thinks it is no big deal, she enjoys herself.  But to me it is a huge deal.  It gives me something to look forward to every other week.  It gets me out of the house.  It gives me someone other than my mom to talk to.  So look around, you may see someone who needs a little help.  You might think it was nothing but you might have made that person’s day a lot more happier.

Living With Wolfram Syndrome – Adam Zwan

Counting My Blessings

AdamHave you ever seen the movie Jack?  In case you have not, Robin Williams (Jack) is the lead character who has a rare condition causing him to age three times as fast on the exterior.  This is a good comparison when speaking of Wolfram Syndrome because as a 27 year old Wolfram patient I am, quote unquote, about 90 years old internally.  Thus, it is like living the life of Jack but inside out. 

The rapid aging and deterioration of my central nervous system has resulted in many health complications that usually occur later in life.  These health complications I am troubled with are prevalent in the lives of almost all Wolfram patients beginning at birth.  In my own lifetime, I have experienced Diabetes, chronic kidney failure, decreased vision, decreased hearing, loss of taste, loss of smell, and a weakened immune system making me more vulnerable to the everyday free radicals.  My aging central nervous system is probably why I can relate so well to elderly individuals; conversations always contain “yes sir, been there, done that”, and “yes, I have that problem too.” 

Wolfram may cut my life short but it just reminds me to be thankful for what I do have and count my blessings.  Not being bed ridden, still having brain activity and still being able to use my legs and arms makes me realize that Wolfram syndrome may be a tough bullet to chew but things could always be worse.  So long as the Wolfram research and the Snow Foundation are doing well, I choose to keep fighting and hoping for new developments. 

Living With Wolfram Syndrome – Lauren Gibilisco

I mentioned last week about feeling like a prisoner in my own home. Let me explain it a little further.

Photo of Lauren Gibilisco

Lauren Gibilisco

This is what it is like for me day to day in my own home. During the summer in Nebraska it is very warm here. I cannot be outside long if it is above 70 degrees. So in the summer I am pretty much stuck in the house. But the same thing goes inside the house. I need the temperature to be no higher than 65 degrees in the house. This is what is comfortable for me but it freezes my Mom and Dad. I also feel bad because it makes our air conditioning bill so high. Any hotter and I have trouble sleeping and exercising. I love to exercise but I can only do it a little at a time because I get so overheated. So, when I am home I either just exercise or watch TV. I only watch what I have seen before because I know what they are saying and doing. But, unfortunately it becomes a little boring watching the same shows over and over again.

Last week I was able to leave the house and go to an outside wedding. There was a nice breeze and it was a little above 70. I was able to enjoy the wedding because I was just standing there. I could only stay for about an hour though because I began to get overheated.

The winter time is a little better for me. I am able to exercise more and go outside to chill out if I become too overheated. It used to be that it was hard going outside if there was snow on the ground. Everything was white and I couldn’t see where anything was, like the sidewalk or street. Now my vision has gotten so much worse so it doesn’t really matter anymore.

I do not say these things for pity or to depress anyone. These are just the cold hard facts of living daily with Wolfram Syndrome. So that is why I sometimes feel like a prisoner in my own house. But I wouldn’t change anything. This is who I am and I love being who I am. So if you ever see anyone outside in the winter wearing only a T­-shirt and shorts, don’t worry it’s just me.

Wolfram Syndrome Q&A

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.

Photo of Dr. Fumihiko Urano

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.

Move Forward and Keep Fighting the Fight

Barclay and I are moving forward! As parents you want to do everything possible to provide the best life for your children.
Raquel TV

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!