Tag Archive for: Treatment for WS

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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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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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

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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.
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Calpain Inhibitor and Ibudilast Rescue β cell Functions in a Cellular Model of Wolfram Syndrome

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

Significance

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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Effect of 4-phenylbutyrate and valproate on dominant mutations of WFS1 gene in Wolfram syndrome

Publication: Springer Link | Publication Date: March 26, 2020

Authors: K. Batjargal, T. Tajima, E. F. Jimbo & T. Yamagata

Abstract

Purpose

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

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