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

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.
Read more

/by

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

/by

Wolfram Syndrome 1 Gene Regulates Pathways Maintaining Beta-Cell Health and Survival

Publication: Nature.com | Publication Date: February 14, 2020

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

Abstract

Wolfram Syndrome 1 (WFS1) protein is an endoplasmic reticulum (ER) factor whose deficiency results in juvenile-onset diabetes secondary to cellular dysfunction and apoptosis. The mechanisms guiding β-cell outcomes secondary to WFS1 function, however, remain unclear. Here, we show that WFS1 preserves normal β-cell physiology by promoting insulin biosynthesis and negatively regulating ER stress. Read more

/by

Liraglutide restores chronic ER stress

Publication: nature.com | Publication Date: November 23, 2017

Authors: Theodora Panagaki, Maria Michael & Christian Hölscher

Abstract

Growing evidence suggests that agonists of glucagon-like peptide (GLP-1) receptor exert neuroprotective and neurorestorative effects across a range of experimental models of neuronal degeneration, and, recently, a pilot clinical trial of Liraglutide in Alzheimer’s disease patients showed improvements in cerebral glucose consumption that signifies disease progression. Read more

/by
,

Clinical Trial Update by Dr. Barrett — January 2024

Tim Barrett update for Winter TreatWolfram newsletter

Dear friends and colleagues,

I hope everyone is keeping OK and are keeping warm enough in this cold weather. Our research teams have kept busy and I would like to use this letter to keep you updated on our progress.

The TREATWOLFRAM trial is now in its final year. It has been a long journey to get here, navigating medicine manufacture problems, BREXIT, Covid, and supply issues. Thank you to all the participants who have supported the trial with their involvement. Our trials unit team, Amy Lamb, Lewis James Victoria Homer and Darren Barton, are working hard to make sure all the information that participants have kindly supplied, will be ready to be analysed when the trial ends in October 2024. There has been an update from the UK Medicines Regulator (MHRA) to remind patients and the public about the safety precautions we all need to follow for people taking sodium valproate. Anyone female under 55 years who may be taking sodium valproate, needs to have a safety check with their doctor each year. It is important that sodium valproate should not be taken by women who may be pregnant, as there is a risk of significant harm to the baby. There is helpful information on this UK Government website: https://www.gov.uk/guidance/valproate-use-by-women-and-girls.

Read more

/by

Listen to Episode #26 Wolfram Syndrome Expertise from Dr. Fumihiko Urano from the Podcast “It Happened to Me”

Read more
/by

Help our campaign #givingtuesday

Our mission to create a world without Wolfram syndrome. Our goal is to raise $25,000 this year. We need your help to get us there. Help us Spread the word about our campaign and reach our $25,000 goal http://thesnowfoundation.org/donate/  

/by

Together we give #givingtuesday

One week left to Giving Tuesday. Let’s make a Historic day of giving for The Snow Foundation. Spread the word, gather colleagues, friends and family to donate. http://thesnowfoundation.org/donate/

/by

Join the Generosity Movement #givingtuesday

“I have found that among its other benefits, giving liberates the soul of the giver.” Maya Angelou 

Spread the word and help us reach our goal of $25,000, start a campaign for The Snow Foundation http://thesnowfoundation.org/donate/  

/by