New Rabbit Holes for MANF and Wolframs I had read
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Posted On: 05/15/2022 12:00:29 AM
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New Rabbit Holes for MANF and Wolframs
I had read the updates/intro of Dr. Dermat at 'Institut des Neurosciences de Montpellier INSERM (French National Lab) into Wolfram's back in Feb. They mentioned working on a family of proteins, but were coy about which one(s). Another org, the Eye Foundation, that works with Snow Foundation basically confirms this is referring to neurotrophic factos although it could be referring to NCS1 or BDNF. The Eye Hope Foundation is a Belgian/Norwegian Wolfram's charity led by Lode Carnel who has a son with Wolfram's. The Eye Hope Foundation began collecting proposals for research funding back in summer of 2020 and selected one on MANF in November 2020. They'd previously funded several projects for around €200k, including MAND at Dr. Urano's lab. Accepted proposals were to have a study length of 24-36 months, meaning we could hear about this later this year or next. They also fund research by lead investigator Mario Plaas from University of Tartu, Estonia. Think of this guy as the Fumi Urano of Eastern Europe. I am now curious if this organization is or is related to @amyde on twitter
There is a Wolfram Symposium that occurs every 2 years and should occur in Paris this summer. Perhaps we will get some MANF updates then
http://www.eyehopefoundation.org/en
http://www.inmfrance.com/inmfrance-j3/index.php/fr/
https://mmdn.umontpellier.fr/en/
"Spring update 2021
29/04/2021
Dear Friends,
It’s almost half a year since our last update. We hope that you all are in good health and doing well.
In the meantime, we have read and analysed the R&D projects that we received after our call for projects and selected to continue with two of them.
One project solely funded by Eye Hope Foundation is continuing the work by M. Plaas in Estonia on the WFS1 rat. In my opinion this is still the best animal model available to date of Wolfram Syndrome. The project will evaluate neutrophic factors, look at GLP1 / GIP co-agonists and gene therapy as a treatment for Wolfram syndrome. With their established baseline from the previous projects, they have a good comparison base.
Another project was picked in cooperation with the Snow Foundation where we will fund part of the work by B. Delprat and his team in Montpellier. The project also uses gene therapy for administering a protein in a mouse model of WFS1. In parallel the group looks also at a zebrafish model of WFS1.
We wish that we could fund many more projects but after a corona year we are happy we can contribute at least a bit of funding to these two groups.
Besides trying to find a better treatment and managing our daily lives, we as parents have a duty to prepare our kids for the future. Victor is a very positive boy and attending sixth grade in the local international school. As a preparation for the transition to the Middle Years Program, he completed his exhibition project. As a topic of choice, he focused on different types of syndromes (“No surprise”). As part of his work, he performed a 24 km sponsored walk for Eye Hope Foundation collecting a significant amount of funding. He got excellent grades and below are screenshots of his first and last page.
We are very proud of his attitude in life.
On behalf of Eye Hope Foundation,
Lode Carnel"
Research Supported by The Snow Foundation
Dr. Benjamin Delprat
University of Montpellier, France
My projects are focused on elucidating Wolfram syndrome molecular mechanisms and more particularly to study the role of the alterations of communication between two intracellular organelles named the endoplasmic reticulum (ER) and mitochondria, one of the key pathways in the disease. Based on this impairment, we are developing two therapeutical strategies to stop the progression of Wolfram syndrome. Associated with a prompt diagnosis, we are optimistic that the manifestations of the disease can be halted in a timely manner, decreasing the probability to develop neurological and sensorineural symptoms.
Our first strategy is a pharmacological approach. We identified a strong and potent target expressed at the ER-mitochondria junction that interacts with Wolframin, the protein responsible for WS. Its activation restored the cellular alterations in patients’ fibroblasts and the altered behaviors observed in mouse and zebrafish models. Using a phenotypic screening in zebrafish, we already identified novel chemical entities that bind to our relevant target. Following these encouraging results, we are optimizing the molecules that will be tested in cells and in our different animal models. A multi-system screening method (zebrafish and mouse models) approach will be used to screen the panel of molecules and highlight compound that can eventually be used to treat WS patients.
We are also developing an innovative gene therapy. Based on recent studies in the lab, we have envisioned a different approach from what is currently developed. We decided to express a partner protein of Wolframin but not Wolframin itself. The size of this protein allowed us to use viral transfection using a virus already proven efficient in other disorders. By developing a unique gene therapy, which will be delivered systemically, we are hoping to stop the progression of the disease, body-wise, contrarily to the currently explored strategies. Our preliminary data in both zebrafish and mouse models of the disease are very encouraging. We are currently testing the long-lasting effects of the gene therapy as well as its impacts on the different symptoms of the syndrome.
I had read the updates/intro of Dr. Dermat at 'Institut des Neurosciences de Montpellier INSERM (French National Lab) into Wolfram's back in Feb. They mentioned working on a family of proteins, but were coy about which one(s). Another org, the Eye Foundation, that works with Snow Foundation basically confirms this is referring to neurotrophic factos although it could be referring to NCS1 or BDNF. The Eye Hope Foundation is a Belgian/Norwegian Wolfram's charity led by Lode Carnel who has a son with Wolfram's. The Eye Hope Foundation began collecting proposals for research funding back in summer of 2020 and selected one on MANF in November 2020. They'd previously funded several projects for around €200k, including MAND at Dr. Urano's lab. Accepted proposals were to have a study length of 24-36 months, meaning we could hear about this later this year or next. They also fund research by lead investigator Mario Plaas from University of Tartu, Estonia. Think of this guy as the Fumi Urano of Eastern Europe. I am now curious if this organization is or is related to @amyde on twitter
There is a Wolfram Symposium that occurs every 2 years and should occur in Paris this summer. Perhaps we will get some MANF updates then
http://www.eyehopefoundation.org/en
http://www.inmfrance.com/inmfrance-j3/index.php/fr/
https://mmdn.umontpellier.fr/en/
"Spring update 2021
29/04/2021
Dear Friends,
It’s almost half a year since our last update. We hope that you all are in good health and doing well.
In the meantime, we have read and analysed the R&D projects that we received after our call for projects and selected to continue with two of them.
One project solely funded by Eye Hope Foundation is continuing the work by M. Plaas in Estonia on the WFS1 rat. In my opinion this is still the best animal model available to date of Wolfram Syndrome. The project will evaluate neutrophic factors, look at GLP1 / GIP co-agonists and gene therapy as a treatment for Wolfram syndrome. With their established baseline from the previous projects, they have a good comparison base.
Another project was picked in cooperation with the Snow Foundation where we will fund part of the work by B. Delprat and his team in Montpellier. The project also uses gene therapy for administering a protein in a mouse model of WFS1. In parallel the group looks also at a zebrafish model of WFS1.
We wish that we could fund many more projects but after a corona year we are happy we can contribute at least a bit of funding to these two groups.
Besides trying to find a better treatment and managing our daily lives, we as parents have a duty to prepare our kids for the future. Victor is a very positive boy and attending sixth grade in the local international school. As a preparation for the transition to the Middle Years Program, he completed his exhibition project. As a topic of choice, he focused on different types of syndromes (“No surprise”). As part of his work, he performed a 24 km sponsored walk for Eye Hope Foundation collecting a significant amount of funding. He got excellent grades and below are screenshots of his first and last page.
We are very proud of his attitude in life.
On behalf of Eye Hope Foundation,
Lode Carnel"
Research Supported by The Snow Foundation
Dr. Benjamin Delprat
University of Montpellier, France
My projects are focused on elucidating Wolfram syndrome molecular mechanisms and more particularly to study the role of the alterations of communication between two intracellular organelles named the endoplasmic reticulum (ER) and mitochondria, one of the key pathways in the disease. Based on this impairment, we are developing two therapeutical strategies to stop the progression of Wolfram syndrome. Associated with a prompt diagnosis, we are optimistic that the manifestations of the disease can be halted in a timely manner, decreasing the probability to develop neurological and sensorineural symptoms.
Our first strategy is a pharmacological approach. We identified a strong and potent target expressed at the ER-mitochondria junction that interacts with Wolframin, the protein responsible for WS. Its activation restored the cellular alterations in patients’ fibroblasts and the altered behaviors observed in mouse and zebrafish models. Using a phenotypic screening in zebrafish, we already identified novel chemical entities that bind to our relevant target. Following these encouraging results, we are optimizing the molecules that will be tested in cells and in our different animal models. A multi-system screening method (zebrafish and mouse models) approach will be used to screen the panel of molecules and highlight compound that can eventually be used to treat WS patients.
We are also developing an innovative gene therapy. Based on recent studies in the lab, we have envisioned a different approach from what is currently developed. We decided to express a partner protein of Wolframin but not Wolframin itself. The size of this protein allowed us to use viral transfection using a virus already proven efficient in other disorders. By developing a unique gene therapy, which will be delivered systemically, we are hoping to stop the progression of the disease, body-wise, contrarily to the currently explored strategies. Our preliminary data in both zebrafish and mouse models of the disease are very encouraging. We are currently testing the long-lasting effects of the gene therapy as well as its impacts on the different symptoms of the syndrome.
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