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Ongoing Clinical Trial of AMX0035 in patients with Wolfram Syndrome

Dr. Fumihiko Urano
Washington University School of Medicine, USA

Dear Friends,

I hope you had a wonderful summer. As the number of patients referred to us continues to grow, our team feels an even greater urgency to develop safe and effective treatments for Wolfram syndrome. I’m pleased to share the latest updates with you:

Ongoing Clinical Trial of AMX0035 in patients with Wolfram Syndrome

We have been collaborating with Amylyx Pharmaceuticals to advance the development of AMX0035, a novel oral medication with the potential to halt or delay the progression of Wolfram syndrome, based on its mechanisms of action and pre-clinical studies. The trial began in April 2023, and the interim results were announced in April 2024. According to Amylyx, the interim analysis of the ongoing Phase 2 clinical trial of AMX0035 for Wolfram syndrome, which involved eight participants assessed at Week 24, revealed encouraging outcomes. Participants demonstrated improvements in pancreatic function and glycemic control, as indicated by C-peptide levels and other markers of glucose metabolism. This contrasts with the typical disease progression expected in Wolfram syndrome. All eight participants met the prespecified responder criteria, showing either improvement or stabilization of their condition, as assessed by both the Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) scales. Furthermore, the majority of participants reported some improvement in vision. Importantly, AMX0035 was generally well-tolerated by all participants, supporting its potential as a therapeutic option for this rare and devastating disorder.

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Dr. Fumihiko Urano | Washington University School of Medicine, USA | Prilenia Therapeutics


Dr. Fumihiko Urano

Washington University School of Medicine, USA

Dear Friends,

Thank you sincerely for your invaluable support of our collaborative study alongside Prilenia Therapeutics. 

One promising candidate is the Sigma 1 receptor, and we have initiated a collaboration with Prilenia, a biotech company specializing in this field. Together, we are investigating the effects of a drug called pridopidine, which targets the Sigma 1 receptor, in cellular models of Wolfram syndrome. We are grateful to the Snow Foundation in collaboration with Ellie White Foundation for their generous donations, which enables us to conduct this crucial study using cells derived from Wolfram syndrome patients. The study is currently in progress as we explore various experimental conditions to assess the efficacy of pridopidine. We are committed to providing you with regular updates on our progress.

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AMYLYX PHARMACEUTICALS Helios Update

AMYLYX PHARMACEUTICALS
Helios Update

Earlier in February 2024, Amylyx Pharmaceuticals announced that enrollment was completed in the Phase 2 HELIOS clinical trial of AMX0035 (sodium phenylbutyrate and taurursodiol) for the treatment of Wolfram syndrome.

HELIOS is a 48-week exploratory, open-label proof of biology study assessing the effect of AMX0035 on a number of measures, including pancreatic function (mainly pertaining to diabetes), visual function, and Wolfram syndrome disease rating instruments.

The study, being conducted at Washington University in St. Louis, has enrolled 12 adult participants living with Wolfram syndrome, and preliminary results are anticipated in the second half of 2024. Data from this initial study will play an important role in giving Amylyx information needed to make decisions for potential future trials. Amylyx looks forward to sharing the results with the community, including at scientific meetings, when they are available.

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Research Finds Brain Cell Death In Rare Disease Wolfram Syndrome Linked To Mitochondrial Defects

Publication Date: May 22, 2023

Authors: Dr Sovan Sarkar, Professor Timothy Barrett

Significance

In a study published in Stem Cell Reports the Sarkar and Barrett labs have defined the molecular basis of neurodegeneration in Wolfram Syndrome patients carrying the WFS1 gene mutation.

Read the entire research article here

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

Publication: Amylyx Pharmaceuticals, Inc. | Publication Date: April 13, 2023

Authors: Amylyx Pharmaceuticals, Inc.

Significance

Recently published preclinical data demonstrate initial proof-of-concept for the therapeutic development of AMX0035 (sodium phenylbutyrate and taurursodiol) in Wolfram syndrome

Read the entire research article here

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Gene Therapy Updates – Prime Editing

Publication: Washington University School of Medicine | Publication Date: September 18, 2022

Authors: Fumi URANO, MD, PhD

Significance

I have some exciting updates on our gene therapy development.

The root cause of Wolfram syndrome is pathogenic changes in the WFS1 gene.

Read the entire research article here

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Urano publishes research on the connection between loss of WFS1 function and ER stress-mediated inflammation

Publication: Washington University School of Medicine | Publication Date: June 10, 2022

Authors: Fumihiko Urano, MD, PhD

Significance

On March 25, Fumihiko Urano, MD, PhD and colleagues had their research titled “Loss of Function of WFS1 Causes ER Stress-Mediated Inflammation in Pancreatic Beta-Cells,” published in “Frontiers in Endocrinology.”

Read the entire research article here

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Longitudinal Assessment of Neuroradiologic Features in Wolfram Syndrome

Publication: American Society of Neuroradiology | Publication Date: October 29, 2020

Authors: A. Samara, H.M. Lugar, T. Hershey, and J.S. Shimony

Significance

Wolfram syndrome is a rare genetic disease with characteristic brain involvement. We reviewed the brain MR images of patients with Wolfram syndrome to determine the frequency and characteristics of common neuroradiologic findings

Read the entire research article here

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Multiple Retinal Anomalies in Wfs1-Deficient Mice

Publication: MDPI.org | Publication Date: August 4, 2020

Authors: Arleta Waszczykowska, Agnieszka Zmyslowska, Marcin Braun, Marilin Ivask, Sulev Koks, Piotr Jurowski, and Wojciech Mylnarski

Significance

To investigate retinal thickness and wolframin expression disorders in Wolfram syndrome 1 gene knockout (Wfs1KO) mice compared to their wild-type (WT) littermates.

Read the entire research article here

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Longitudinal Progression of Diabetes Mellitus in Wolfram Syndrome

Publication: American Diabetes Association | Publication Date: June 2020

Authors: Mary Katherine Ray, Tamara Hershey, Ling Chen, Neil H. White, and Bess A. Marshall

Significance

The purpose of this study was to examine progression of DM, measured by beta-cell function, in WFS patients over time. N=44 (25F/19M) participants with genetically confirmed WFS attended the Washington University Wolfram Research Clinic from 2010-2019.

Read the entire research article here

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