Endoplasmic-Reticulum Calcium Depletion and Disease

Publication: ncbi.nlm.nih.gov | Publication Date: January 7, 2016

Authors: Fumihiko Urano

Abstract

The endoplasmic reticulum (ER) as an intracellular Ca2+ store not only sets up cytosolic Ca2+ signals, but, among other functions, also assembles and folds newly synthesized proteins. Alterations in ER homeostasis, including severe Ca2+ depletion, are an upstream event in the pathophysiology of many diseases. Read more

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Endoplasmic reticulum stress and glucose homeostasis

Publication: pubmed.ncbi.nlm.nih.gov | Publication Date: July 14, 2011

Authors: Damien Abreu, Rie Asada, John M. P. Revilla, Zeno Lavagnino, Kelly Kries, David W. Piston & Fumihiko Urano

Abstract

Purpose of review: Balancing glucose homeostasis is crucial to maintain appropriate energy and metabolic state. Chronic hyperglycemia with insulin resistance and development of type II diabetes mellitus is a growing health and health-economic threat. Read more

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Disease Modifying Treatments for Optic Neuropathies Including Gene Therapy

Publication: ncbi.nlm.nih.gov | Publication Date: September 30, 2016

Authors: Patrick Yu-Wai-Man, Marcela Votruba, Florence Burté, Chiara La Morgia, Piero Barboni, and Valerio Carelli

Abstract

Mitochondrial optic neuropathies constitute an important cause of chronic visual morbidity and registrable blindness in both the paediatric and adult population. It is a genetically heterogeneous group of disorders caused by both mitochondrial DNA (mtDNA) mutations and a growing list of nuclear genetic defects that invariably affect a critical component of the mitochondrial machinery. Read more

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Decreasing Beta-cell Dysfunction in Wolfram Syndrome

Publication: ncbi.nlm.nih.gov | Publication Date: February 13, 2014

Authors: Linshan Shang, Haiqing Hua, Kylie Foo, Hector Martinez, Kazuhisa Watanabe, Matthew Zimmer, David J. Kahler, Matthew Freeby, Wendy Chung, Charles LeDuc, Robin Goland, Rudolph L. Leibel, and Dieter Egli

Abstract

Wolfram syndrome is an autosomal recessive disorder caused by mutations in WFS1 and is characterized by insulin-dependent diabetes mellitus, optic atrophy, and deafness. To investigate the cause of β-cell failure, we used induced pluripotent stem cells to create insulin-producing cells from individuals with Wolfram syndrome. Read more

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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

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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

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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

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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).
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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

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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

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