Publication: eyehopefoundation.org | Publication Date: February 14, 2020
Authors: Professor Hamel
A reliable mouse model of Wolfram syndrome with the visual degradation has been developed. Initial tests with AAV-drive gene therapy has shown promising results in those mice to partially rescue the vision of wolfram syndrome patients. Read more
Publication: ncbi.nlm.nih.gov | Publication Date: July 29, 2013
Authors: Shu-Jen Chen, Julie Johnston, Arbans Sandhu, Lawrence T. Bish, Ruben Hovhannisyan, Odella Jno-Charles, H. Lee Sweeney, and James M. Wilson
The ability to regulate both the timing and specificity of gene expression mediated by viral vectors will be important in maximizing its utility. We describe the development of an adeno-associated virus (AAV)-based vector with tissue-specific gene regulation, using the ARGENT dimerizer-inducible system. Read more
Publication: nature.com | Publication Date: October 14, 2021
Authors: Cairns, G., Burté, F., Price, R. et al.
Wolfram syndrome (WS) is an ultra-rare progressive neurodegenerative disorder defined by early-onset diabetes mellitus and optic atrophy. The majority of patients harbour recessive mutations in the WFS1 gene, which encodes for Wolframin, a transmembrane endoplasmic reticulum protein. Read more
Publication: wolframsyndrome.wustl.edu | Publication Date: February 1, 2022
Authors: Fumihiko Urano
We recently identified a WFS1 gene variant associated with a mild form of Wolfram syndrome in the Ashkenazi Jewish population. This WFS1 gene variant, WFS1 c.1672C>T (p.Arg558Cys) is prevalent in the Jewish population, and 1/30 Jewish people are carriers. Read more
Publication: The Faseb Journal | Publication Date: April 15, 2020
Authors: Tom T. Fischer, Lien D. Nguyen, Barbara E. Ehrlich
Wolfram syndrome (WS) is an orphan, autosomal recessive neuroendocrinological disease that affects approximately 1 in 500,000 people worldwide. Patients develop diabetes mellitus, diabetes insipidus, optical atrophy, and hearing loss and usually die in their 30s. The majority of cases are attributed to mutations in a single gene, WFS1, which encodes for the protein wolframin. Despite the known genetic cause, there is currently no direct treatment for WS. This lack of therapy is because the regular functions of wolframin, and the pathophysiological consequences following the loss of intact WFS1, remain elusive. Read more
Publication: Science Translational Medicine | Publication Date: April 22, 2020
Authors: Kristina G. Maxwell, Punn Augsornworawat, Leonardo Velazco-Cruz, Michelle H. Kim, Rie Asada, Nathaniel J. Hogrebe, Shuntaro Morikawa, Fumihiko Urano, Jeffrey R. Millman
Endoplasmic reticulum (ER) stress-mediated cell death is an emerging target for human chronic disorders, including neurodegeneration and diabetes. However, there is currently no treatment for preventing ER stress-mediated cell death. Here, we show that mesencephalic astrocyte-derived neurotrophic factor (MANF), a neurotrophic factor secreted from ER stressed cells, prevents ER stress-mediated β cell death and enhances β cell proliferation in cell and mouse models of Wolfram syndrome, a prototype of ER disorders. Our results indicate that molecular pathways regulated by MANF are promising therapeutic targets for regenerative therapy of ER stress-related disorders, including diabetes, retinal degeneration, neurodegeneration, and Wolfram syndrome.
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Publication: PNAS.org | Publication Date: July 21, 2020
Authors: Lien D. Nguyen, Tom T. Fischer, Damien Abreu, Alfredo Arroyo, Fumihiko Urano, and Barbara E. Ehrlich
Wolfram syndrome is a rare multisystem disease characterized by diabetes insipidus, diabetes mellitus, optic nerve atrophy, and deafness (DIDMOAD). It is primarily caused by mutations in the Wolfram syndrome 1 gene, WFS1. As a monogenetic disorder, Wolfram syndrome is a model for diabetes and neurodegeneration. There is no effective treatment for this invariably fatal disease. Here we characterize WFS1 as a regulator of calcium homeostasis and subsequently target calcium signaling to reverse deficits in a cellular model of Wolfram syndrome.
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Publication: Springer Link | Publication Date: March 26, 2020
Authors: K. Batjargal, T. Tajima, E. F. Jimbo & T. Yamagata
Wolfram syndrome (WS) is a rare disorder caused by mutations in WFS1 that is characterized by diabetes mellitus, optic atrophy, sensorineural deafness, diabetes insipidus, and neurodegeneration. This disease is usually inherited as an autosomal recessive trait, but an autosomal dominant form has been reported. Read more
Publication: Nature.com | Publication Date: February 14, 2020
Authors: Damien Abreu, Rie Asada, John M. P. Revilla, Zeno Lavagnino, Kelly Kries, David W. Piston & Fumihiko Urano
Wolfram Syndrome 1 (WFS1) protein is an endoplasmic reticulum (ER) factor whose deficiency results in juvenile-onset diabetes secondary to cellular dysfunction and apoptosis. The mechanisms guiding β-cell outcomes secondary to WFS1 function, however, remain unclear. Here, we show that WFS1 preserves normal β-cell physiology by promoting insulin biosynthesis and negatively regulating ER stress. Read more
Publication: nature.com | Publication Date: November 23, 2017
Authors: Theodora Panagaki, Maria Michael & Christian Hölscher
Growing evidence suggests that agonists of glucagon-like peptide (GLP-1) receptor exert neuroprotective and neurorestorative effects across a range of experimental models of neuronal degeneration, and, recently, a pilot clinical trial of Liraglutide in Alzheimer’s disease patients showed improvements in cerebral glucose consumption that signifies disease progression. Read more
The Snow Foundation is a collective voice for Wolfram syndrome patients, working towards a cure for Wolfram syndrome and developing novel therapies for diabetes, vision loss, hearing loss and neurodegeneration.
P.O. Box 50224 Clayton, MO 63105
(402) 694-1354