The Washington University Lab Working to Cure Jewish Wolfram Syndrome

At Washington University School of Medicine in St. Louis, Missouri, a dedicated team of scientists is working to change the future for people living with Wolfram syndrome. 

Led by Dr. Fumihiko (Fumi) Urano, MD, PhD, one of the world’s foremost experts on the condition, the lab has become a global center for research and clinical care, especially for families affected by the Ashkenazi Jewish variant of Wolfram syndrome.

The team at WashU Medicine is actively researching and developing novel therapies to target the Jewish Variant of Wolfram syndrome. These therapies could potentially take the form of oral medications or novel gene-editing approaches. 

Dr. Fumihiko (Fumi) Urano, MD, PhD, Wolfram symdrome expert at the Wolfram Clinic at Washington University Medical Center.

Gene editing to correct WFS1 in Wolfram Syndrome

Most recently, Dr. Fumihiko and his team have been investigating gene editing as a potential treatment for Wolfram syndrome and its Ashkenazi Jewish subtype. 

Gene editing is transforming how we treat rare genetic disorders by targeting the root cause — mutations in our DNA. Unlike traditional treatments that only manage symptoms, gene editing can directly fix the faulty gene responsible for the disease.

WashU researchers are using an advanced gene editing method called base editing to address the limitations of current gene editing methods. This technique avoids making breaks in the DNA and can precisely correct single-letter mutations like those found in the WFS1 gene.

So far, the research has shown that base editing works well in both lab-grown cells from patients and in mouse models. By correcting the mutation, it restores normal gene function while keeping the body’s natural control of the gene in place.

This project includes preclinical testing in both lab and animal testing and could one day lead to human clinical trials. If successful, the research potentially could lead to a one-time, permanent treatment for Wolfram syndrome — hopefully within the next five to ten years. 

Regenerative therapy for optic nerve atrophy 

One of the most common symptoms for the Ashkenazi Jewish subtype of Wolfram syndrome is optic nerve atrophy. In the WashU Medicine lab, Dr. Fumihiko and his team are developing regenerative therapies that use a neurotrophic factor, or a protein, called MANF. This protein protects optic nerve cells and helps them stay healthy and function better.

Preclinical studies in mice are currently underway, including in mice genetically modified to model Wolfram Syndrome. Scientists are now focused on delivering the MANF protein directly to the eye to help prevent or repair optic nerve damage.

The team at WashU is currently working in collaboration with patient organizations like nonprofit or advocacy groups to develop and expedite clinical trials — which are expected to begin within the next five to seven years. 

Clinical trials of potential drug treatments

One of the most promising therapies for Wolfram Syndrome involves AMX0035, a drug in development by Amylyx Pharmaceuticals and WashU Medicine. This oral medication aims to slow the progression of the condition. 

Phase 2 clinical trials began in April 2023 to enhance care for patients with Wolfram syndrome.

The WashU team is still in the process of publishing the results, but the interim data can be found at: 

• AMYLYX Pharmaceuticals

• NeurologyLive

Patient-centered care

The multidisciplinary Wolfram Clinic at Washington University Medical Center serves patients from across the United States and around the world. offers comprehensive care, including genetic evaluations, counseling, personalized care plans, and access to current and emerging therapies. Patients work closely with a team of experts in neurology, endocrinology, ophthalmology, and other specialties.

Through innovative science, compassionate care and strong partnerships with patients and families, Dr. Urano and his colleagues at Washington University are laying the foundation for new treatments and lasting hope.

Read more about Dr. Fumihiko (Fumi) Urano, MD, PhD here.