Q&A Wolfram syndrome

Here are the questions I often get. There is currently no effective treatment for Wolfram syndrome, creating an urgent need to develop novel therapeutics. Our current strategy is to delay the progression of common manifestations using small molecules (i.e., drugs), and then develop stem cell-based therapies.
http://wolframsyndrome.dom.wustl.edu/

Q: What is Wolfram syndrome?

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.

Q: What is diabetes mellitus?

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.


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.

Are genetically engineered cells safe?

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.

Thank you for reading today's blog. I hope you have a wonderful day. Cordially, Fumi Urano
http://wolframsyndrome.dom.wustl.edu/

Raise Awareness October 29, 2014

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 each state 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. 
http://wolframsyndrome.dom.wustl.edu/

Thank you for reading this blog. I hope you have a wonderful day. Kindly, Fumi Urano

Combating optic nerve degeneration in Wolfram syndrome

One of the most important developments in my team is our collaboration with Dr. Raj Apte's 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.

Thank you for reading this blog. I hope you have a wonderful day. Kindly, Fumi Urano

Wolfram syndrome website at Washington University Medical Center

I hope you help us spread the word to raise awareness of Wolfram syndrome, the most difficult form of diabetes. http://wolframsyndrome.dom.wustl.edu/

Kindest regards,
Fumi Urano

Stem cell-based therapies Q&A-Fate of transplanted cells

I received an intelligent and important question yesterday.

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. I hope you have wonderful Monday. Take care, Fumi Urano

Stem cell-based therapies - How long?

Here is another question related to stem cell-based therapies. 

Q: How long will it take for stem cell-based therapies to become mainstream? 

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. 

Thank you for reading this blog. Enjoy wonderful Sunday. Fondly, Fumi Urano

Stem cell-based therapy Q&A - Medical Use

Here is another question I often get.

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

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. 

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.

Thank you for reading this blog. I hope you have a wonderful weekend. Kindly, Fumi Urano

Wolfram syndrome UK

Wolfram syndrome UK 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 Dr. Barrett, a pioneer in Wolfram syndrome research. I respect and appreciate their efforts. Thank you, Thank you, Thank you.

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.

Thank you for reading this blog. I hope you will have a wonderful weekend. I am grateful and hopeful. Kindly, Fumi Urano

Stem cell-based therapy Q&A 1

I have been receiving many questions related to stem cell-based therapy for Wolfram syndrome and diabetes. I would like to share these questions and my answers with you.

Q: What are stem cells?

A: Stem cells are a type of cells that have potential to develop into many different cell types, including insulin producing cells and eye cells, in our body. There are two types of stem cells that can be utilized for treatment. These are induced pluripotent stem cells (iPS cells) and embryonic stem cells (ES cells).

iPS cells are derived from skin fibroblasts. These cells may be useful for designing personalized medicine. ES cells are derived from fertilized eggs. My team is focusing on iPS cells derived from patients' skin cells because of many reasons.

Thank you for reading this. Please feel free to contact me if you have any questions. I am sending kind thoughts toward you. Take care, Fumi Urano

Stem cell-based therapy in motion

It has been just published that a stem cell-based therapy for macular degeneration is safe and effective for macular degeneration, one of the leading causes of blindness.
http://www.theguardian.com/science/2014/oct/15/stem-cell-success-in-treating-macular-

We should follow their success and I am in constant motion to make this happen for patients with Wolfram syndrome. Stem cell-based therapeutics and gene-based diagnostics will change the world. 

Thank you for reading this blog. I am sending kind thoughts toward you! Kindly, Fumi Urano

Bringing change to the clinical trial process

I hope we can bring change to to the clinical trial processes for rare diseases. Each patient is different. The conventional clinical trial design may not be feasible. I welcome the proposed changes described in the article.
http://www.forbes.com/sites/medidata/2014/09/25/rare-disease-patient-voices-bring-change-to-the-clinical-trials-process/

I feel quite hopeful and encouraged because of new initiatives and partnerships I have been involved in. I hope you have a wonderful day today. I feel something wonderful is going to happen. Kindly, Fumi Urano

Raise awareness in the younger generation

NIH has been helping us raise awareness of rare diseases in the younger generation. To bring new therapeutics based on genetic medicine to our patients, we need support from the general public. The following web is quite helpful to achieve this.
http://science.education.nih.gov/customers.nsf/MSDiseases.htm

Thank you for reading this blog. I hope you have a wonderful day. Take care, Fumi Urano

Gene-based diagnostics can help patients

My team has been working on establishing gene-based diagnostics for rare forms of diabetes. This article in New Yorker reminds us of the importance of genetic medicine and gene-based diagnostics. http://www.newyorker.com/magazine/2014/07/21/one-of-a-kind-2

We clearly need new and innovative therapeutics for each genetic disorder. To accomplish this, we need new diagnostics to figure out what's really going on in each patient. The medicine has changed dramatically in the past 5 years due to the development of next generation gene sequencing, gene editing, and stem cell-based therapeutics. We should bring these innovative diagnostics and therapeutics to out patients swiftly. We need to raise awareness of these.

Thank you for reading this blog. It is a beautiful day here in St. Louis. I hope you have a wonderful Sunday. Cordially, Fumi Urano

Raise Awareness - Spread the word

I always feel that we should raise awareness of rare diseases to provide a cure. We certainly need new therapeutics. We need small molecules to halt the progress. We need stem cell-based and genome-engineering-based therapies to provide a cure. My team has been working on small molecules, stem cells, and genome editing. However, we need to raise awareness of the disease. To bring our new treatments to our patients, we need funds and supports from the FDA and our local IRBs. To get support, we need to raise awareness. The Jack and JT Snow Foundation, the Ellie White Foundation, the Team Alejandro, the Team Ian, the Wolfram syndrome patient support group, the Wolfram syndrome UK, and association du syndrome de Wolfram are working hard to raise awareness. Please help us spread the word. http://wolframsyndrome.dom.wustl.edu/

Thank you for your encouragement and continued support. I hope you have a wonderful weekend. Kindly, Fumi Urano

Molecular surgery update-a new type of gene therapy

We have been trying to correct the mutations in the WFS1gene that cause disease manifestations using a new technology called CRISPR-CAS. This is a new type of gene therapy. We could finally correct one mutation in iPS cells from one patient with Wolfram syndrome. It took a few months, but this is a great first step. We will keep on trying!

Thank you for reading this blog. I feel grateful. Have a wonderful day. Onward & upward, Fumi Urano

We can utilize iPS cells to model our disease

We are actively using induced pluripotent stem cells (iPS cells) to develop therapeutics for Wolfram syndrome. What are iPS cells? These are a type of stem cells derived from our skin cells. iPS cells can be differentiated into any types of cells. So we can use these cells to replace damaged tissues in patients with Wolfram syndrome and other disorders.

In addition, we can use iPS cells to model our disease. Professor Doug Melton at Harvard, a prominent scientist who has developed a method to create insulin-producing cells from stem cells, talked about iPS cells in his interview. In short, we can model our disease using iPS cells to understand the mechanisms and test potential therapies.

Professor Melton said,
"If you wanted to design a thought experiment to get at the cause of type 1 diabetes, it would go as follows. We would take a person with diabetes and clone them 100 times. We would put the clones in different environments, feed them different foods, give them different viruses and every five minutes take blood samples, do pancreatectomies and try to figure out the primary cause. Obviously we are not going to do this experiment, but iPS cells give us an alternative, which is why I am so excited."
http://www.newscientist.com/article/dn17729-doug-melton-finding-a-cure-for-diabetes.html#.VD2F_ildV19

Thank you for reading this blog. I am hopeful. Take care, Fumi Urano

Translational Medicine

Dr. Francis Collins is my role model and I have been trying to emulate what he has done on cystic fibrosis and progeria. Dr. Collins is a lucent speaker. His presentation on translational medicine at TED MED was fabulous, and I hope you will watch this when you get a chance. Sam Berns, his friend and patient with progeria, is with him in the video.
https://www.youtube.com/watch?v=spUoPC_TU_8

Thank you for reading this. Please feel free to contact me if you have any questions. I hope you have a wonderful day. Onward and upward, Fumi Urano
*Please help us spread the word.
http://wolframsyndrome.dom.wustl.edu/

In Memory of Sam by Dr. Collins

Dr. Francis Collins is a world-famous medical researcher and my role model. He is a god in genetic medicine. He has been working on multiple rare diseases. Currently he is director of the National Institutes of Health. I often read one of his blogs on Sam Berns, his friend and patient with a rare disease.
http://directorsblog.nih.gov/2014/01/12/in-memory-of-sam-berns/
I was inspired by this and wrote a blog on one of our patients, Ms. K.
http://wolframsyndrome.blogspot.com/2014/02/in-memory-of-k.html
I feel the same for our patients with Wolfram syndrome. Many of them are my friends and I would like to help them. We found a few candidate drugs that can theoretically delay the progression of the disease. I hope we can bring these drugs to our patients soon. We also need to develop gene therapy and regenerative therapy to provide a cure.  I believe in the power of genetic medicine. I need more help and funds, but I am committed to make these happen. 

Thank you for reading this blog. I am sending kind thoughts toward you. Warmly, Fumi Urano

Genetic testing and VUS

What is "VUS"? VUS stands for variant of unknown significance. VUS means that DNA sequence variation is previously unreported and is of the type which may or may not be causative of the disorder. 

Some variations are tightly linked to the disease, and some variations are clearly not linked to the disease. There are still many variants of unknown significance. If a patient has the VUS, clinicians and medical geneticists work together and figure out whether the VUS is associated with the disease or not.

Thank you for reading this blog. I hope you have a wonderful day. Take care, Fumi Urano

Genetic testing?

What is genetic testing? It is the process of using medical tests to look for clinically relevant changes in a person's genes. 

Genetic testing has utility in
-Diagnosis
-Prognosis
-Therapeutic decision making

Currently, genetic testing for Wolfram is useful for making diagnosis and estimating prognosis. I believe that it will be useful for therapeutic decision making in the next few years. I feel that genetic testing will be a critical component in many aspects of healthcare management.

Thank you for reading this blog. I hope you have a wonderful Sunday. Warmly, Fumi Urano

How many beta cells do we have?

A few days ago, someone asked me, "How many beta cells do we have?" Based on the literature, we have "1 billion" insulin-producing beta cells in the pancreas. If we lose 50% of them, we may have symptoms of diabetes. So to provide a cure for diabetes, we need to create "1 billion" beta cells using stem cells for each patient. We also need to stop beta cell dysfunction and death. In Wolfram syndrome, beta cell loss is probably mediated by dysregulated intra-cellular calcium homeostasis. So we are trying to fix this using small molecules (i.e., drugs). 

Thank you for reading this blog. I hope you will have a wonderful Saturday. I am sending kind thoughts toward you. Kindly, Fumi Urano

Stem cell-based therapy for diabetes

I heard wonderful news last night. Professor Doug Melton's group at Harvard developed a method for creating massive quantities of insulin-producing cells from stem cells.
http://news.harvard.edu/gazette/story/2014/10/giant-leap-against-diabetes/

One of the biggest challenges in the field of regenerative medicine is to create large quantities of specific types of cells from stem cells. It was impossible to make large quantities of insulin-producing beta cells from stem cells, but now it is POSSIBLE.  

Gene-based diagnostics and Stem cell-based therapeutics are key components for providing a cure for Wolfram syndrome, Type 1 diabetes, and other chronic conditions. We should keep on moving forward.

Thank you for reading this blog. I hope you have a wonderful Friday. Kindly, Fumi Urano

NIH funds research collaborations of 22 physician-scientists to study rare diseases

I read the news about the NIH's initiative for supporting rare disease research. NIH will fund physician scientists at 22 consortia to investigate new treatments for patients with rare diseases. This is great news.
http://www.nih.gov/news/health/oct2014/ncats-08.htm
To be part of it, we need to develop a common theme weaving through different rare diseases. I think that our common theme would be "endoplasmic reticulum disease." I will look for other diseases related to endoplasmic reticulum dysfunction to create a new research program. I believe this will help us develop treatments for Wolfram syndrome and Wolfram-related disorders.

Thank you for reading this blog. I hope you have a wonderful Thursday. Take care, Fumi Urano

Center of Regenerative Medicine

I attended a meeting of our newly-formed "Center of Regenerative Medicine" yesterday.

http://devbio.wustl.edu/REGMED/index.php

As I mentioned in my previous blogs, it would be essential to develop stem cell-based therapies for a cure for Wolfram syndrome, Type 1 diabetes, and other chronic disorders. Our new center is a wonderful platform for us to collaborate with other researchers who are interested in developing regenerative therapies.

Thank for reading this blog. I hope you have a wonderful Wednesday. Fondly, Fumi Urano

Dominant allele? Is it a key?

What is "allele"? An allele is an alternative form of a gene that is located at a specific position on a specific chromosome. We have two alleles for each trait. Wolfram syndrome is an autosomal recessive disease. This means most patients have two pathogenic alleles. We have recently found patients who only have one pathogenic allele. This allele is called "dominant." I feel that this allele may be a key to understand the mechanisms of Wolfram syndrome.

Thank you for reading this blog. I understand that this one is a little difficult for lay people. I just wanted to share my thoughts. I welcome any feedback. Take care, Fumi Urano

Drug Repurposing

One of our current options for the development of new therapeutics for Wolfram syndrome is  “drug repurposing.” What is "drug repurposing"? Drug repurposing is the application of known drugs to new diseases. We can save a lot of money and time with this approach. Dr. Freda Lewis-Hall, Chief Medical Officer at Pfizer, discusses this strategy in the following video (39 seconds). 
https://www.youtube.com/watch?v=LRFhWqEULgI

Thank you for reading this blog. I hope you will have a wonderful Monday. I feel that something wonderful is going to happen to us this week. With confidence, Fumi Urano

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.

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.

Raise Awareness Today

The Jack and JT Snow Research Foundation has been helping us raise awareness and develop therapeutics for Wolfram syndrome. Recently, the Snow Foundation created a nice cartoon summarizing the potential manifestations of Wolfram syndrome. This is helpful and I am grateful for their sincere and continued efforts.
http://thesnowfoundation.org/research/

I hope you will have a wonderful weekend and enjoy the beginning of the fall season. Take care, Fumi Urano

Upstream and Downstream

My mentor, Dr. Aldo Rossini, often told me about "upstream" and "downstream" in medicine. "Upstream" means our efforts on developing new treatment for our patients. Downstream means our efforts on managing our patients. Both are important, and I keep on doing my my best for both.

Thank you for reading this blog. I hope you will have a fabulous Friday. Kindly, Fumi Urano

from Aldo Rossini, MD

Raise Awareness

Many people help us raise awareness of Wolfram syndrome. If you know Type 1 diabetes patients who have other unusual symptoms such as optic nerve atrophy, please contact us. They may have Wolfram or other unusual forms of diabetes. They may need different treatments.

One of the major challenges for physicians is to provide answers to patients with mysterious conditions that have long eluded diagnosis. Patients suffer from mysterious conditions without diagnosis and effective treatments. Many of our Wolfram patients experienced this. So we need to keep on raising awareness of Wolfram syndrome and other rare genetic diseases. Please help us spread the word.

Thank you for reading this blog. I am sending kind thoughts toward you. Take care, Fumi Urano

Share our experiences - Blogs of our patients

I am always impressed by our patients. Many of them are always positive although they are facing the major challenge. I learn from them and grow with them. I am  trying to help them. In reality, they help me keep on going and encourage me all the time. To achieve a cure, we need to help each other. I hope you read their blogs. You will learn something from them.
http://thesnowfoundation.org/blog/

I feel that we are all connected. Thank you for reading my blog. I hope you will have a wonderful day today. Warmest regards, Fumi Urano