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Zebrafish Screen of compounds for individual or combination treatment of WS

Principal Investigator Dr.Benjamin Delprat, Montpellier, France

  • With help from the WS patient community and a special shout-out to our dear friend Nufar, a list of 30 widely available and potentially therapeutic compounds was compiled to be evaluated for the potential treatment of WS.
  • We are completing negotiations to test these compounds individually and in combination in a WS zebrafish model.
  • We aim to determine the most effective and accessible compounds that may serve as a treatment “cocktail” to aid in slowing the progression of symptoms in WS.
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MRI evaluation of Neurological findings in WS

Principal Investigators Dr. Lucas Fernandez Brillet, and GemaEsteban Bueno, MD, Barcelona, Spain

  • Broad categories of neurodegenerative findings in WS have been proposed and established through prior work done by WS researchers.
  • This project, proposed by Dr. Lucas Brillet, aims to determine in more detail the areas of the brain that are affected in WS, and to stratify these results with respect to different WFS1 mutations.
  • This project will help us better understand the natural history of WS, and better understand mutation-specific symptoms that may be amenable to different types of treatment to slow progression.
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Mapping the WFS1 Interactome in Wolfram Syndrome: From Mechanisms to Therapeutic Leads

Principal Investigator Dr. Mariana Igoillo-Esteve, Co-Investigator Ane Olazagoitia-Garmendia, Brussels, Belgium

  • New potential WFS1 interactors were discovered by Dr. Igoillo-Esteve in 2025.
  • This work aims to validate the new interactome data obtained in 2025, uncover the molecular pathways in which they are involved, and characterize their roles in cellular function, ER stress, and survival.
  • Following this interactome identification, this project will prioritize and test compounds targeting the most relevant pathways identified.

This project aims to:

  • Uncover cellular mechanisms that result in Wolfram syndrome by identifying molecular functions of WFS1
  • Pave the way for innovative therapeutic strategies.
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Development of a High-Throughput Sensor Library to Correct Over 60% of Known Pathogenic Variants in WS

Principal Investigator Dr. Samagya Banskota, Boston, USA

  • This project will attempt to make gene editing available to all WS patients who have a variant that involves a single base pair change (missense variant). Over 60% of people with WS with documented genotypes may benefit from this strategy.
  • This approach is important because a single attempt at gene editing for WS, right now, will only treat one patient/variant at a time.
  • This work by Dr. Banksota will attempt to create a “Platform” approach in which the basic gene-editing “machinery” will be the same, only the specific variant to be corrected will differ. In this way, the same drug/treatment could be used for over 60% of people with WS, regardless of their many different variants.
  • Such a platform approach will save many millions of dollars in drug development costs and many years of drug development time.
  • This project is very timely, given the gene editing preclinical data being generated now and in the near future by Drs. Urano, Banskota, and De Groef. If successful, this platform library will open the door to applying this same technique to all WS patients with missense variants concurrently in a potential gene editing/base editing clinical trial for WS.
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Treatment Development Collaboration with Odylia Therapeutics

  • The Snow Foundation has partnered with Odylia Therapeutics to bridge the gap between preclinical/bench research and clinical trials.
  • Odylia provides expert guidance and advice to take potential treatments from the lab to clinical trial and accelerate treatment development.
  • We will continue to work together to forge a path forward for treatments like gene editing and regenerative therapy for WS
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AntiSense Oligonucleotides (ASOs), for the treatment of Wolfram syndrome by La Jolla Labs

La Jolla Labs, USA

  • Members of The Snow Foundation met with representatives from La Jolla Labs to investigate the role of RNA directed gene therapy, specifically AntiSense Oligonucleotides (ASOs), for the treatment of Wolfram syndrome.
  • La Jolla Labs undertook an investigation to determine the potential for ASO application, specifically for the treatment of autosomal dominant Wolfram-related disorder.
  • The head of research at LJL presented a review of the potential use of ASO therapy for WS based on disease biology and different ASO strategies.
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WFS1 Gene Therapy to correct chronic inflammation due to Wolframin loss of function mutations

Principal Investigators- Drs. Raniero Chimienti and Giulio Frontino, Milan, Italy

  • This work is done in collaboration with Telethon Foundation, Italy
  • This project is designed to test whether immune cells that have been genetically corrected can help improve the inflammatory symptoms of Wolfram syndrome in a mouse model.
  • By transplanting genetically corrected WS immune cells into mice with Wolfram syndrome, researchers will study whether inflammation is reduced and whether the progression of Wolfram syndrome symptoms can be slowed by addressing/reducing inflammation.
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Clinical evaluation of Idebenone as a Potential Treatment for Wolfram Syndrome

Extending into 2026

Principal Investigator-Felipe Chicani, MD, Sao Paolo, Brazil

  • This patient comparison study will evaluate WS patients who have been treated with idebenone compared to an untreated control group to determine if idebenone can help slow the progression of WS symptoms, with a focus on vision loss.
  • This project is currently in the planning stage and will last a minimum of 12-24 months
  • Data from the past several years, current data, and data going forward will be evaluated.
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Gene Therapy Treatment of Wolfram Syndrome

Principal investigator Dr. Cécile Delettre-Cribaillet, INM, Montpelier, France

Extending into 2026:

  • This work will be done in conjunction with a grant from the Be a Tiger Foundation
  • This is an ongoing project evaluating and validating the potential for WFS1 wildtype gene transfer as atreatment for Wolfram syndrome.
  • Preclinical data have already shown the ability of gene therapy to correct symptoms of Wolfram syndrome in a WFS1 knock-out model.
  • New steps in the project include ensuring that overexpression of WFS1 in cells will not impair this correction and validating the already reported promising effects of gene therapy in a knock-in mouse model that more precisely mirrors human WS.
  • This complete data set will help us to determine the efficacy of gene therapy for preserving vision in WS
  • This work will provide validation and efficacy data to move gene therapy closer to development for WS.
  • Corrected WFS1 will be delivered with a retina-specific vector, directly to the retina with direct injection to the eye in a WS knock-in (more similar to humans than a knock-out) mouse model.
  • Corrected WFS1 will be delivered systemically with a different vector, also in a knock-in mouse model, to determine if multiple organs (including pancreas and retina) can be treated in WS with a single treatment.
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From the Desk of Dr. Sarah Gladstone

Chief Medical and Scientific Officer

From the Desk of the Dr. Sarah Gladstone, CMO/CSO

As we enter 2026 and look back on 2025, it’s remarkable how much progress has been made in such a short time.Scientific research can be challenging—there are periods when progress feels slow and frustrating, and answers seem just out of reach. Then there are moments when things finally come together: the data start to make sense, key questions are answered, and important milestones are achieved. We are now in a time of data coming together. What follows is a look back at the progress made in 2025, and an exciting look ahead at the possibilities now opening up for the year to come. Treating Wolfram syndrome is not a one-size-fits-all approach. The condition itself is not the same for everyone. Each person with Wolfram syndrome has a unique combination of symptoms based on their specific genetic variation and individual biology. Because of this, treatment may differ from person to person depending on age, genetic findings, and which symptoms are most prominent. Even though treatments may differ, the overall treatment strategy follows a clear and consistent path. The goals remain the same:

  • First, to slow the progression of cell stress and dysfunction;
  • Second, to prevent ongoing cell death;
  • Ultimately, to replace damaged cells with new, healthy cells.

Based on the expressed needs of the Wolfram syndrome community, current treatment efforts focus on the central nervous system (including the brain, retina, vision, and hearing), the pancreas (diabetes), and bowel and bladder function, while also addressing other associated symptoms. It has been an incredibly busy and fulfilling year…. and decade! We are profoundly thankful to our donors and supporters—you are the reason this work happens. Your generosity fuels every step forward, and we are so grateful to have you as part of this community. Because of you, we are moving forward with energy, hope, and momentum. The year ahead is shaping up to be an exciting one, and we can’t wait to celebrate and share our progress with you in 2026!

— Dr.Sarah Gladstone

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