Saturday, March 29, 2014
Meeting with Spanish Patients with Wolfram syndrome, a physician and a researcher
This morning, I had a chance to meet with patients with Wolfram syndrome and their doctors in Spain through the Skype. I had a chance to explain our progress towards the treatment and cure for Wolfram syndrome. We all know that it is not a simple endeavor, but we all have the same goal. It is always my pleasure and privilege to meet with and serve for patients with Wolfram syndrome and their families. Thank you for your patience and encouragement. Take care and have a nice weekend.
Sunday, March 23, 2014
Important Development and Collaborations
I believe we should have three components for the treatment of Wolfram syndrome.
1. Delay the progression of the disease with existing FDA-approved drugs.
This is our current major focus, and we have a rising candidate. We are looking for a simple way to assess the efficacy of this drug in patients and are trying to collect blood samples from patients and their siblings. In parallel, we are also looking for a new group of drugs that can delay the progression of the disease with a company. All of these drugs seem to be related to cellular calcium homeostasis.
2. Enhance the viability of eye cells, brain cells, and pancreatic beta cells.
In Wolfram syndrome, brain cells, eye cells, and beta cells in the pancreas are sensitive to cell stress and susceptible to cell death due to the mutations in the WFS1 gene. We are developing a method to make brain cells, eye cells, and pancreatic beta cells, more resistant to cell stress. We have identified an interesting hormone-like molecule produced in our body called MANF. MANF can make our cells more resistant to cell stress-mediated cell death. We are trying to establish a collaboration with a pharmaceutical company to develop a drug based on our findings.
3. Replace damaged tissues using patients' skin cells.
As I mentioned in my previous blogs, we have created induced pluripotent stem cells (iPS cells) using skin cells from patients. We are creating brain cells and eye cells using these iPS cells. These cells have been useful to dissect out the mechanisms of the disease and test the efficacy of candidate drugs. We are also replacing a pathogenic WFS1 gene part with a healthy WFS1 gene part in these cells. In the future, we will use these cells for replacing damaged tissues.
1. Delay the progression of the disease with existing FDA-approved drugs.
This is our current major focus, and we have a rising candidate. We are looking for a simple way to assess the efficacy of this drug in patients and are trying to collect blood samples from patients and their siblings. In parallel, we are also looking for a new group of drugs that can delay the progression of the disease with a company. All of these drugs seem to be related to cellular calcium homeostasis.
2. Enhance the viability of eye cells, brain cells, and pancreatic beta cells.
In Wolfram syndrome, brain cells, eye cells, and beta cells in the pancreas are sensitive to cell stress and susceptible to cell death due to the mutations in the WFS1 gene. We are developing a method to make brain cells, eye cells, and pancreatic beta cells, more resistant to cell stress. We have identified an interesting hormone-like molecule produced in our body called MANF. MANF can make our cells more resistant to cell stress-mediated cell death. We are trying to establish a collaboration with a pharmaceutical company to develop a drug based on our findings.
3. Replace damaged tissues using patients' skin cells.
As I mentioned in my previous blogs, we have created induced pluripotent stem cells (iPS cells) using skin cells from patients. We are creating brain cells and eye cells using these iPS cells. These cells have been useful to dissect out the mechanisms of the disease and test the efficacy of candidate drugs. We are also replacing a pathogenic WFS1 gene part with a healthy WFS1 gene part in these cells. In the future, we will use these cells for replacing damaged tissues.
Sunday, March 16, 2014
Wolfram: Oxidative Stress and Endoplasmic Reticulum
Is antioxidant good for Wolfram syndrome? Although we don't have clear scientific evidence at this point, it is possible that antioxidants could be beneficial for Wolfram syndrome patients.
Accumulating evidence in my research group strongly suggests that endoplasmic reticulum (ER) dysfunction can lead to oxidative stress. Oxidative stress means that reactive oxygen species (ROS) exceeds the ability of our body to counteract their harmful effects. Our body has the ability to deal with certain amount of ROS, but if there is too much ROS, it leads to oxidative stress. In theory, antioxidants should be able to mitigate ER stress-mediated oxidative stress and its harmful effects. We are particularly interested in this concept in the context of optic nerve atrophy and neurodegeneration in Wolfram.
We still don't have clear evidence that antioxidants are beneficial for Wolfram syndrome patients. So I recommend that you consult with your physician if you are interested in taking antioxidants.
Accumulating evidence in my research group strongly suggests that endoplasmic reticulum (ER) dysfunction can lead to oxidative stress. Oxidative stress means that reactive oxygen species (ROS) exceeds the ability of our body to counteract their harmful effects. Our body has the ability to deal with certain amount of ROS, but if there is too much ROS, it leads to oxidative stress. In theory, antioxidants should be able to mitigate ER stress-mediated oxidative stress and its harmful effects. We are particularly interested in this concept in the context of optic nerve atrophy and neurodegeneration in Wolfram.
We still don't have clear evidence that antioxidants are beneficial for Wolfram syndrome patients. So I recommend that you consult with your physician if you are interested in taking antioxidants.
Sunday, March 9, 2014
Patient-based therapeutics part 7- Making eye cells
I am on my way to Japan to establish a collaboration with a major Japanese medical center on our Wolfram syndrome project. Why Japan? The reason is very simple. They have a technology to make eye cells from patient-derived induced pluripotent stem cells (iPS cells). If my research group can constantly make eye cells from Wolfram syndrome iPS cells, we can understand the mechanisms of optic atrophy in Wolfram syndrome and test the efficacy of our candidate drugs using these eye cells. This is also another opportunity to raise awareness of Wolfram syndrome.
As I repeatedly mentioned in my previous blogs, Wolfram is a weapon to combat diabetes and blindness. I believe that Wolfram is an accelerated form of diabetes and blindness. Many of us will experience beta cell death and death of eye cells later in our lives. A drug that can delay the progression of Wolfram may be helpful for us when we get old.
As I repeatedly mentioned in my previous blogs, Wolfram is a weapon to combat diabetes and blindness. I believe that Wolfram is an accelerated form of diabetes and blindness. Many of us will experience beta cell death and death of eye cells later in our lives. A drug that can delay the progression of Wolfram may be helpful for us when we get old.
Saturday, March 8, 2014
What can you do to improve "neurogenic bladder" ?
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 is 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.
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.
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