An important article on MANF has been just published by a group in Europe. The article shows that MANF is essential for survival of pancreatic beta cells.
http://www.cell.com/cell-reports/abstract/S2211-1247(14)00201-0
What is MANF? As I mentioned in my previous blog, we discovered that MANF (mesencephalic astrocyte-derived neurotrophic factor) was secreted from pancreatic beta cells and neurons when their endoplasmic reticulum calcium was depleted. We also claimed that MANF could be a promising biomarker and therapeutic target for Wolfram and type 1 diabetes.
http://wolframsyndrome.blogspot.com/2014/01/manf-wolfram-and-diabetes-what-is-manf.html
Why is this article important for us? This article supports our theory that MANF is an important therapeutic target for Wolfram and diabetes! I was really encouraged by this article. Currently, we are focusing on the clinical applications of MANF in Wolfram syndrome, diabetes, and other endoplasmic reticulum-related disorders. I hope we can bring you good news soon!
Sunday, April 13, 2014
Friday, April 11, 2014
An update on our efforts to develop treatment for Wolfram syndrome
Our progress on Wolfram syndrome has been featured at the website of the Washington University's Institute of Clinical and Translational Sciences. This article succinctly and correctly summarizes our progress. I have unwavering faith that our sincere efforts will lead to a cure for Wolfram syndrome.
Urano Wolfram Syndrome Study
In 2011 Fumihiko Urano, MD, PhD, Samuel E. Schechter Professor of Medicine, received a 2 year pilot grant from the ICTS for the study begun by his late colleague M. Alan Permutt, “Translating Mechanisms for a Genetic Neurodegenerative Disease to New Therapies”. This project established a yearly clinic for children with Wolfram syndrome (WS), a rare childhood disease characterized by insulin dependent diabetes mellitus and neurological dysfunctions in an effort to uncover biomarkers for monitoring disease progression. In exciting reports/updates provided just one-year post award, the multidisciplinary team including Bess Marshall and Tamara Hershey and supported by the Human Imaging Unit and Pediatric Clinical Research Unit has:
- Identified an enzyme implicated in ER stress as a molecular target for WS treatment.
- Uncovered FDA-Approved drugs that block activation this enzyme and cell death by exploiting banked iPSCs (in the Core facility) derived from patient skin cells. These pluripotent stem cells will help in the identification of therapeutics to treat WS and may eventually be used to replace damaged tissues resulting from this monogenic disorder.
- Working with the Office of Technology Management, several biotech and pharmaceutical companies have been identified with overlapping interests in advancing drugs of potential benefit to patients with WS. The ultimate goal would be to establish clinical trials in the US with extensions in Japan and Europe.
These translational discoveries utilized an important pediatric patient population, combining multiple assessment methods and resources drawn from a dedicated basic science and clinical community working collaboratively to understand the molecular mechanism and identify actionable targets for the treatment of Wolfram Syndrome.
Presented our progress on Wolfram syndrome at the Keystone Symposium
I just presented our progress on Wolfram syndrome at the Keystone symposium. It was a great opportunity to raise awareness Wolfram syndrome. I could feel that many researchers and physicians became interested in the link between Wolfram syndrome and type 1 diabetes. I could make new connections!
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.
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