Entries by The Snow Foundation

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A soluble endoplasmic reticulum factor as regenerative therapy for Wolfram syndrome

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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Calcium mishandling in absence of primary mitochondrial dysfunction drives cellular pathology in Wolfram Syndrome

We showed that Wolframin (WFS1) protein is enriched at mitochondrial-associated ER membranes and that in patient-derived fibroblasts WFS1 protein is completely absent. These findings support a loss-of-function pathogenic mechanism for missense mutations in WFS1, ultimately leading to defective calcium influx within mitochondria.

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GLP-1 receptor agonist liraglutide has a neuroprotective effect on an aged rat model of Wolfram syndrome

Wolfram syndrome is a rare genetic spectrum disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration, and ranges from mild to severe clinical symptoms. There is currently no treatment to delay, halt, or reverse the progression of Wolfram syndrome, raising the urgency for innovative therapeutics for this disease. Here, we summarize our vision for developing novel treatment strategies and achieving a cure for Wolfram-syndrome-spectrum disorder.

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Current Landscape of Treatments for Wolfram Syndrome

Wolfram syndrome is a rare genetic spectrum disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration, and ranges from mild to severe clinical symptoms. There is currently no treatment to delay, halt, or reverse the progression of Wolfram syndrome, raising the urgency for innovative therapeutics for this disease. Here, we summarize our vision for developing novel treatment strategies and achieving a cure for Wolfram-syndrome-spectrum disorder.

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The Laboratory of Molecular & Cellular Signaling and its mission in Wolfram Syndrome research

The Laboratory of Molecular & Cellular Signaling (LMCS; https://gbiomed.kuleuven.be/english/research/50000618/50753344), co-directed by Prof. Jan B. Parys & Prof. Geert Bultynck, is part of the Department of Cellular and Molecular Medicine at KU Leuven. The research team studies intracellular Ca2+ signals and Ca2+-controlled processes such as cell death and cellular bio-energetics in human cells. Furthermore, the team […]

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Amarantus Bioscience

MANF Therapeutics is developing mesencephalic astrocyte-derived neurotrophic factor (MANF) as a therapeutic protein for the treatment of certain protein-misfolding and neurological disorders. MANF is currently in pre-clinical development as a disease modifying treatment for Parkinson’s disease and Wolfram’s Syndrome. In Wolfram’s, many of the key disease etiologies, including vision loss, hearing loss, diabetes and neurodegeneration have protein […]

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