Recently we have identified a family of molecules with the capacity to stimulate significantly the growth of retinal ganglion cells in vitro in a model of optic atrophy. We developed a zebrafish model with an optic atrophy and we have treated these fishes with one of these molecule. We used increasing doses of molecules to measure the toxicity and determine the most effective dose to protect the optic nerve. We have determined the dose with the best effect and confirmed that treatment with this molecule can prevent optic nerve developmental delay in vivo in our model of optic neuropathy. We are studding the mechanism of action of this molecule and using it in several model of Wolfram syndrome We look forward to a clear indication of the possibility of using this molecule in the future development of a treatment for Wolfram syndrome.
Gene therapy project using WFS1 is also important for us. We have synthetized a novel AAV2/9-WFS1 vector to treat all affected tissues in a previously established mouse model of Wolfram syndrome. After injection of the vector in young mice, we have checked that the vector could transduce all affected tissues including, eye, ear, brain and pancreas. We are now evaluating the efficacy of this gene transfer on visual and auditory function of our mouse model.
http://thesnowfoundation.org/wp-content/uploads/2019/06/snow-foundation_logo.svg00The Snow Foundationhttp://thesnowfoundation.org/wp-content/uploads/2019/06/snow-foundation_logo.svgThe Snow Foundation2024-03-29 20:31:422024-03-29 20:31:42Dr. Cecile Delettre | Neuroscience Institute of Montpellier, France
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.
Once again, we extend our heartfelt thanks for your generous support, which is instrumental in advancing our mission to find a cure for Wolfram syndrome and bring hope to those affected by this condition.
With grace and gratitude,
Fumi
Fumihiko Urano, MD, PhD, FACMG
Professor of Medicine and of Pathology & Immunology
Samuel E. Schechter Endowed Professor in Medicine
Director, Wolfram Syndrome/WFS1-related disorders Registry & Clinical Study and WFS1 clinic at BJC HealthCare
http://thesnowfoundation.org/wp-content/uploads/2019/06/snow-foundation_logo.svg00The Snow Foundationhttp://thesnowfoundation.org/wp-content/uploads/2019/06/snow-foundation_logo.svgThe Snow Foundation2024-03-29 20:22:352024-03-29 20:28:50Dr. Fumihiko Urano | Washington University School of Medicine, USA | Prilenia Therapeutics
In my lab, we are developing concomitantly two therapeutic strategies: a pharmacological approach and a gene therapy. To achieve these goals, we are working with suited animal models: two transgenic mouse lines and one zebrafish line. One mouse model and the zebrafish line are deficient for Wolframin, the protein responsible for Wolfram syndrome type 1. The other mouse model has been genetically engineered to mimic a human mutation, recapitulating sensorial deficits (vision and hearing loss) and diabetes. We are hoping to treat vision and hearing, as well as central neurodegeneration.
– Update –
* We have explored the impact of the absence of Wolframin or the presence of an abnormal protein in the neurons of our mouse models (neurons of the hippocampus and cortex) as well as in patients’ fibroblast (cells cultured from the skin). Our findings suggest considering the use of the same therapeutic targets in both cases, thus opening treatment perspectives for patients carrying a mutation leading to an abnormal protein (Wolfram-like syndrome).
* Using our zebrafish model of the disease, we have validated our gene therapy strategy. Based on these encouraging results, we are now investigating the outcomes of this approach in our mouse models.
Our gene therapy approach corrected the memory deficit and locomotor coordination alteration at least one month after the injection of the virus. In addition, the virus is efficiently transducing the affected brain structure such as cerebellum, hippocampus, or cortex and lasting in time.
We are now exploring vision and hearing loss of our preclinical models, following the injection of the virus.
http://thesnowfoundation.org/wp-content/uploads/2019/06/snow-foundation_logo.svg00The Snow Foundationhttp://thesnowfoundation.org/wp-content/uploads/2019/06/snow-foundation_logo.svgThe Snow Foundation2024-03-29 19:46:232024-03-29 19:46:23Dr. Benjamin Delprat | University of Montpellier, France
Dr. Timothy Barrett’s Update | University of Birmingham, United Kingdom
Dear friends and colleagues,
I hope everyone is keeping OK. I have 3 items to update you on.
Firstly, the TREATWOLFRAM trial is continuing to progress well. We had an independent Data Monitoring Committee meeting in January. This is chaired by Professor Karen Morrison, an honorary consultant in adult neurology, who previously led the highly specialised service for adults with Wolfram syndrome. The Data Monitoring Committee reviewed the unblinded data. I am pleased to say that they had no safety concerns, and were happy for the trial to continue to completion. Following this meeting, our Trial Steering Committee met, chaired by Professor Marc Peschanski, Director of INSERM, a large research institute outside Paris. We discussed the trial progress so far, and plans for acting on the results at the end of the trial. The last participant will complete the trial at the end of October 2024. We will then have 2-3 months to collect any outstanding data from study sites. The Clinical Trials Unit…..
read in full here.
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.
McCarthy Building Company’s annual Dan Licari Memorial Fishing Tournament raised $13,445.00 for the Snow Foundation to support the Bieser family in their fight against Wolfram Syndrome.. THANK YOU!!!!
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This year, we are funding four projects worth almost $400,000.
Please donate today to support our community. Your gift will make a significant difference and help us achieve our goal.
For More Information: https://thesnowfoundation.org/2024-support-drive-could-you-help/
http://thesnowfoundation.org/wp-content/uploads/2019/06/snow-foundation_logo.svg00The Snow Foundationhttp://thesnowfoundation.org/wp-content/uploads/2019/06/snow-foundation_logo.svgThe Snow Foundation2024-03-18 10:00:542024-03-10 15:35:412024 Support Drive, could you help?
Join the virtual conference The Snow Foundation and Wolfram Syndrome UK will host on April 13th.The conference will feature four presentations starting at 2:00 pm (BST). Details about the program and registration links will be forthcoming. This bi-annual event aims to educate everyone about the latest research on Wolfram Syndrome.
http://thesnowfoundation.org/wp-content/uploads/2019/06/snow-foundation_logo.svg00The Snow Foundationhttp://thesnowfoundation.org/wp-content/uploads/2019/06/snow-foundation_logo.svgThe Snow Foundation2024-03-15 10:00:362024-03-12 15:25:37SAVE THE DATE APRIL 13TH, Wolfram Syndrome Global Virtual Conference RESEARCH UPDATES
The Snow Foundation is grateful for the support it has received from people around the world. We would like to express our appreciation to Markus Klasenar for putting us on the map in Germany. Thanks to their fundraising efforts, we have raised 2,650 euros for our Quest for A Cure!
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Dr. Fumihiko Urano Washington University School of Medicine, USA
Dr. Fumihiko Urano
Washington University School of Medicine, USA
Dear Friends,
I want to take a moment to express my deep gratitude for your unwavering belief in and support of our mission to find a cure for Wolfram syndrome. Your enduring encouragement has been a beacon of hope guiding us on this remarkable journey. As we embark on the year 2024, filled with hope and determination to inch closer to our goal of finding a cure, I would like to provide a summary of our progress in the battle against Wolfram syndrome.
Rare Disease Day at NIH 2024
Before I delve into our progress update, I’m excited to share some fantastic news with you. I’ve received an invitation to present our research on Wolfram Syndrome at the Rare Disease Day event held at the National Institutes of Health on February 29, 2024. This event is widely regarded as one of the most prestigious gatherings for rare diseases, offering an excellent platform for us to raise awareness about Wolfram Syndrome. Even if you can’t attend in person, you can still participate by watching my presentation remotely. Here is the link to access it: https://ncats.nih.gov/news-events/events/rdd
Ongoing clinical trial
In partnership with Amylyx Pharmaceuticals, we are actively advancing the development of AMX0035, an innovative oral medication designed to slow or halt the progression of Wolfram syndrome. In 2020, the US FDA granted AMX0035 orphan drug status for Wolfram syndrome. Using data from previous clinical studies, we have developed a protocol to assess the safety and effectiveness of AMX0035. This protocol has been approved by both the US FDA and the Institutional Review Board at Washington University Medical Center. We have initiated a phase 2 clinical trial for adult patients with Wolfram syndrome at Washington University Medical Center, with the first participant starting AMX0035 treatment in April 2023.
Our trial is proceeding smoothly, and we are currently planning our next steps. We have received numerous inquiries about including children in the trial, as well as patients without diabetes and patients with WFS1-related disorders (those who have hearing loss and optic nerve atrophy due to having one pathogenic copy of WFS1). We appreciate your interest and feedback, and we plan to make a formal announcement later this year. Please stay tuned for further updates.
Regenerative Therapy for Optic Nerve Atrophy
Our primary objective is to halt and reverse the progression of low vision resulting from optic nerve atrophy in individuals with Wolfram syndrome. We are pursuing this goal through regenerative medicine. Our current strategy involves the administration of a regenerative factor called MANF into the eyes of Wolfram syndrome patients using a viral vector. As you may be aware, our brain naturally produces certain neurotrophic factors like BDNF and CDNF to maintain brain health. MANF is also a neurotrophic factor, but it stands out because it offers protection against Endoplasmic Reticulum (ER) stress, a key molecular mechanism involved in Wolfram syndrome. Additionally, MANF aids in boosting the growth of ER-stressed cells. We are presently conducting preclinical studies using cell and rodent models specifically designed to mimic Wolfram syndrome, in order to evaluate the effectiveness of MANF in addressing optic nerve atrophy. Promising results have emerged from our humanized mouse model of Wolfram syndrome, indicating the potential of this innovative approach to treat other causes of low vision as well. While there are undoubtedly several challenges ahead, our ultimate aim is to initiate a regenerative therapy trial for optic nerve atrophy within the next 3 to 7 years.
Gene Editing Therapy
The primary cause of Wolfram syndrome stems from a pathogenic alteration within the WFS1 gene. Consequently, the most effective approach to treating Wolfram syndrome involves rectifying these gene mutations. To ensure safety, we have transitioned from using CRISPR to utilizing the more advanced Base Editing (2nd generation) and Prime Editing (3rd generation) techniques to correct the pathogenic changes in the WFS1 gene associated with Wolfram syndrome. These cutting-edge gene editing technologies are currently considered the most advanced methods available. To evaluate the efficacy of this technology, we have generated rodent models featuring pathogenic mutations in the Wfs1 gene that closely mimic those observed in our patients. Our ultimate objective is to apply this therapeutic approach to benefit our patients within the next 5-10 years.
International Consortium
I’d like to present a significant idea to you. After extensive thought and discussions with senior advisers, I’ve made the decision to establish an international consortium focused on Wolfram Syndrome and Related Disorders and join the Rare Diseases Clinical Research Network (https://www.rarediseasesnetwork.org/). I intend to submit a substantial grant application to the National Institutes of Health. Through this consortium, my goals are as follows. I’m pleased to share that The Snow Foundation has graciously agreed to lead the patient organization group for objective #4.
1. Advance our understanding of the clinical manifestations of Wolfram syndrome and related disorders through collaborative clinical research.
3. Investigate genotype-phenotype correlations and identify drug targets.
4. Improve awareness among scientists, physicians, and the general public regarding the unique needs of patients with Wolfram syndrome and related disorders with patient organizations.
Clinical service
To improve the clinical care for patients with Wolfram syndrome and WFS1-related disorders, including WFS1-related deafness and optic nerve atrophy, we have been running the WFS1 clinic at the Center for Advanced Medicine, Washington University Medical Center. This clinic has been successful, and I see patients from different states and countries almost every week. I appreciate that the Snow Foundation, the Ellie White Foundation, the Unravel Wolfram Syndrome, and the FB groups related to Wolfram syndrome have referred patients to our clinic. We offer genetic evaluations, education, and counseling for patients and family members of all ages with or suspected to have Wolfram syndrome and WFS1-related disorders. We also provide personalized management plans with other specialists at our medical center and beyond. We accept international patients via our international patient care office. We also accept out-of-state patients.
Patients in the US
If you’re in the US, please call Christine Manning, RN, Nurse Coordinator, at 314-747-7055 or 314-362-3500. Let her know that you or your family member has Wolfram syndrome or WFS1-related medical conditions and need to make an appointment. Once we review your medical records, Dr. Urano or his staff will contact you to discuss which specialists you may need to see.
Sending Medical Records via Fax
Please fax your medical records to 314-747-7065.
Referrals via Fax for both Missouri patients and out-of-state patients
Please fax your referral request to 314-747-7065.
International Patients
International patients are welcome to contact our international patient care office to schedule an appointment by calling +1-314-273-3780 or sending an email to Internationalpatients@wustl.edu.
Conclusion
The encouraging outcomes we’ve witnessed fill us with hope for the future, and we’re dedicated to forging ahead in our mission to bring about meaningful change. Thank you again for your unwavering support. Together, we will persist in our efforts and shine a beacon of hope for those affected by Wolfram syndrome. Here’s to a brighter future on the horizon!
With grace and gratitude,
Fumi
Fumihiko Urano, MD, PhD, FACMG
Professor of Medicine and of Pathology & Immunology
Samuel E. Schechter Endowed Professor in Medicine
Director, Wolfram Syndrome/WFS1-related disorders Registry & Clinical Study and WFS1 clinic at BJC HealthCare
http://thesnowfoundation.org/wp-content/uploads/2019/06/snow-foundation_logo.svg00The Snow Foundationhttp://thesnowfoundation.org/wp-content/uploads/2019/06/snow-foundation_logo.svgThe Snow Foundation2024-03-11 21:14:422024-03-11 21:19:31Groundbreaking research of Dr. Fumihiko Urano at Washington University School of Medicine, USA
Dr. Timothy Barrett’s Update | University of Birmingham, United Kingdom
AMYLYX PHARMACEUTICALS
Join the virtual conference The Snow Foundation and Wolfram Syndrome UK will host on April 13th.The conference will feature four presentations starting at 2:00 pm (BST). Details about the program and registration links will be forthcoming. This bi-annual event aims to educate everyone about the latest research on Wolfram Syndrome.
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