Common variants in WFS1 confer risk of type 2 diabetes

Publication: ncbi.nlm.nih.gov | Publication Date: April 23, 2009

Authors: Manjinder S Sandhu, Michael N Weedon, Katherine A Fawcett, Jon Wasson, Sally L Debenham, Allan Daly, Hana Lango, Timothy M Frayling, Rosalind J Neumann, Richard Sherva, Ilana Blech, Paul D Pharoah, Colin N A Palmer, Charlotte Kimber, Roger Tavendale, Andrew D Morris, Mark I McCarthy, Mark Walker, Graham Hitman, Benjamin Glaser, M Alan Permutt, Andrew T Hattersley, Nicholas J Wareham and Inês Barroso

Abstract

We studied genes involved in pancreatic β cell function and survival, identifying associations between SNPs in WFS1 and diabetes risk in UK populations that we replicated in an Ashkenazi population and in additional UK studies. Read more

/by

Chemical Chaperones in Protein Folding Diseases

Publication: ncbi.nlm.nih.gov | Publication Date: May 12, 2014

Authors: Leonardo Cortez and Valerie Sim

Abstract

Several neurodegenerative diseases are caused by defects in protein folding, including Alzheimer, Parkinson, Huntington, and prion diseases. Once a disease-specific protein misfolds, it can then form toxic aggregates which accumulate in the brain, leading to neuronal dysfunction, cell death, and clinical symptoms. Read more

/by

Chemical Chaperones and Treatment of Diabetes and Wolfram Syndrome

Publication: ncbi.nlm.nih.gov | Publication Date: August 25, 2006

Authors: Umut Özcan, Erkan Yilmaz, Lale Özcan, Masato Furuhashi, Eric Vaillancourt, Ross O. Smith, Cem Z. Görgün, and Gökhan S. Hotamisligil

Abstract

Endoplasmic reticulum (ER) stress is a key link between obesity, insulin resistance, and type 2 diabetes. Here, we provide evidence that this mechanistic link can be exploited for therapeutic purposes with orally active chemical chaperones. Read more

/by

Amylyx Pharmaceuticals Announces First Participant Dosed in Phase 2 Study of AMX0035 for the Treatment of Wolfram Syndrome

Publication: amylyx.com | Publication Date: April 13, 2023

Authors: Amylyx Media Team

CAMBRIDGE, Mass.–(BUSINESS WIRE)– Amylyx Pharmaceuticals, Inc. (NASDAQ: AMLX) (“Amylyx” or the “Company”) today announced that the first participant has been dosed in the HELIOS study, a Phase 2 clinical trial of AMX0035 (sodium phenylbutyrate [PB] and taurursodiol [TURSO]) for the treatment of Wolfram syndrome (WS).
Read more

/by

AAV Vector Retinal Target Gene Transfer Therapy

Publication: eyehopefoundation.org | Publication Date: February 14, 2020

Authors: Professor Hamel

Abstract

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

/by

AAV Vector Gene Transfer Therapy

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

Abstract

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

/by

A mutant wfs1 zebrafish model of Wolfram syndrome manifesting visual dysfunction and developmental delay

Publication: nature.com | Publication Date: October 14, 2021

Authors: Cairns, G., Burté, F., Price, R. et al.

Abstract

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

/by

A mild form of Wolfram syndrome in the Ashkenazi Jewish population

Publication: wolframsyndrome.wustl.edu | Publication Date: February 1, 2022

Authors: Fumihiko Urano

Abstract

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

/by

Neuronal Calcium Sensor 1 (NCS1) as a Potential Drug Target for Treatment of Wolfram Syndrome

Publication: The Faseb Journal | Publication Date: April 15, 2020

Authors: Tom T. Fischer, Lien D. Nguyen, Barbara E. Ehrlich

Abstract

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

/by

Gene-Edited Human Stem Cell-Derived β Cells From a Patient with Monogenic Diabetes Reverse Preexisting Diabetes in Mice

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

Abstract

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.
Read more

/by