Gene Therapy Updates – Prime Editing

Publication: wolframsyndrome.wustl.edu | Publication Date: September 18, 2022

Authors: Fumihiko Urano

I have some exciting updates on our gene therapy development.

The root cause of Wolfram syndrome is pathogenic changes in the WFS1 gene. Therefore, correcting these changes in the WFS1 gene is the best way to treat Wolfram syndrome. Read more

/by

Function of WFS1 and WFS2 in the Central Nervous System: Implications for Wolfram Syndrome and Alzheimer’s disease

Publication: pubmed.ncbi.nlm.nih.gov | Publication Date: February 14, 2020

Authors: Liangping Li, Lalitha Venkataraman, Shuo Chen, Hongjun Fu

Abstract

L.P. Li, L. Venkataraman, S. Chen, and H.J. Fu. Function of WFS1 and WFS2 in the Central Nervous System: Implications for Wolfram Syndrome and Alzheimer’s Disease. NEUROSCI BIOBEHAV REVXXX-XXX,2020.-Wolfram syndrome (WS) is a rare monogenetic spectrum disorder characterized by insulin-dependent juvenile-onset diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing loss, progressive neurodegeneration, and a wide spectrum of psychiatric manifestations. Read more

/by

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

/by

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

/by

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

/by

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

/by

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