USH2025: What We Learned

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The USH2025 International Symposium on Usher Syndrome recently took place in Nijmegen, the Netherlands. This three-day event brought together researchers, clinicians, patient organisations, and members of the Usher syndrome community from around the world including Usher Syndrome Ireland.

The first two days were dedicated to the scientific programme, showcasing the latest research into the genetics, biology, and treatment of Usher syndrome. The third day - known as USH2025 Congrestival - focused on the wider community, celebrating lived experience, advocacy, and connection.

A huge thank you and congratulations to Stichting Ushersyndroom, who organised such an impressive, inspiring, and truly inclusive event. Despite the challenges of different languages and accessibility needs, the team made sure everyone felt welcomed and supported, something that left a lasting impression on all attendees including us.

We were thrilled to meet so many researchers and hear about the latest advances in understanding Usher syndrome, as well as research that could potentially lead to treatments. Equally, it was wonderful to reconnect with old friends and meet new ones from USH organisations around the world, including Stichting Ushersyndroom, Save Sight Now Europe, Usher Initiative Austria, UsherKids UK, Usher Syndrome Coalition, USH1F Collaborative, Usher Syndrome Society, CureUsher UK, and ContactGroup Ushersyndroom. 

The strength of collaborating with other patient organisations is a powerful force by helping to raise awareness, support families, and accelerate research. As Usher Syndrome Ireland continues to grow, these connections are vital to ensuring our community’s voice is heard and that progress is truly global.

Over the first two days, researchers shared the latest research findings and explored future directions in the field. The programme included keynote lectures, abstract presentations, and poster sessions covering a wide range of topics - from gene therapies and disease modelling to diagnostics and patient registries.

Given the sheer amount of knowledge exchanged, it’s impossible for us to summarise everything in detail. However, here are the key highlights from each day that offer a glimpse into the exciting and innovative work currently underway.

Day One opened with a warm welcome from Nico di Milliano and Erwin van Wijk (members of the organising committee)(, who emphasised how the symposium provides a unique chance to build bridges between researchers and foster collaboration and knowledge sharing - a theme that proved true over the following days. 

Honorary Lecture 

The day began with a moving honorary lecture celebrating the life’s work of Prof. Dr. William (Bill) Kimberling, affectionately known as the “godfather of Usher syndrome research.” Prof. Dr. Claes Möller delivered the tribute, highlighting Kimberling’s pioneering contributions to the field, including his instrumental role in identifying the first gene associated with Usher syndrome and establishing genetic testing protocols that have advanced diagnosis and research globally. It was also highlighted how far research into Usher syndrome has progressed since Bill Kimberling’s early days in the field. The growing body of knowledge and the sheer amount of research being conducted today, as evident at this conference and illustrated in a graph shared during the lecture, stand as a testament to his enduring influence. 

Keynote Lecture 1 – Alexander Hoischen, Radboud UMC, Nijmegen 

Prof. Alexander Hoischen presented exciting research on what could be the future of genetic testing: Long Read Sequencing (LRS) technology. This new approach makes it possible, for the first time, to read the entire human genome in far greater detail, helping detect genetic changes that older methods might miss. It could become a powerful first-tier test for rare diseases like Usher syndrome, potentially enabling definitive diagnoses where conventional methods fall short. 

Keynote Lecture 2 – Vasiliki Kalatzis, Institute for Neurosciences of Montpellier

Dr. Vasiliki Kalatzis described how her team’s research further highlights the power of iPSC-derived retinal organoid models in understanding retinal function and dysfunction. By generating retinal organoids from patients with USH2A variants - either syndromic or non-syndromic - they discovered distinct differences in retinal phenotypes between these two groups and shed light on the molecular mechanisms underlying these differences. These results offer crucial insights into how the disease process varies in USH variants, potentially informing more targeted therapeutic approaches for different forms of Usher syndrome. 

Keynote Lecture 3 – Jennifer B. Phillips, Institute of Neuroscience, University of Oregon 

Dr. Jennifer B. Phillips shared her lab’s “two-pronged” approach to researching Usher syndrome using zebrafish models with mutations in several USH genes. Her team is both screening small molecules that might protect photoreceptors from degeneration and exploring CRISPR/Cas9 gene editing and antisense oligonucleotide (ASO) therapies. Their goal is to discover treatments that could preserve vision across the broadest range of Usher patients. 

Between the keynote lectures, seven fascinating abstract presentations covered diverse topics, including: 

• The spectrum of causative genes for Usher syndrome in Japanese patients (Tatsuo Matsunaga) 
• Investigating genetic causes of deafblindness in the Democratic Republic of the Congo (Ismael Byaruhanga) 
• Accurate prevalence calculations of Usher syndrome using genomic datasets (Eliot Shearer) 
• Data hubs and registries, and the importance of early genetic diagnosis for research and healthcare systems (Dominique Sturz) 
• Mapping Usher syndrome gene expression in the developing human inner ear (Wouter van der Valk) 
• The impact of a nonsense mutation in USH2A exon 13 on Müller glial cell health (Rossella Valenzano) 
• Studying USH1C/harmonin functions in Müller glial cells using a humanised USH1C R31* pig model (Yesim Tütüncü ) 

Day Two built on the momentum of the first day with a packed programme of keynote lectures and abstract presentations. The day offered a deep dive into the molecular mechanisms behind Usher syndrome and highlighted some of the most promising therapeutic strategies currently under development.

Keynote Lecture 4 – Marcos Sotomayor, Department of Biochemistry and Molecular Biology, University of Chicago 

Prof. Marcos Sotomayor explored the molecular structures and dynamics of two critical proteins, cadherin-23 (USH1D) and protocadherin-15 (USH1F), which are essential for hearing and balance. Using experimental and computational techniques, his team identified important subdomains within these proteins whose disruption leads to sensory deficits in Usher syndrome. Importantly, this detailed understanding could help design modified versions of protocadherin-15 as potential gene therapy candidates. 

Keynote Lecture 5 – Uwe Wolfrum, Institute of Molecular Physiology, University of Mainz 

Prof. Uwe Wolfrum presented new insights into unexpected disease mechanisms in Usher syndrome types USH1C, USH1G, and USH2C. Beyond their known roles in intracellular transport and structural support, Usher proteins appear to participate in other cellular processes, with defects contributing to disease pathology. These discoveries have revealed novel biomarkers and potential new therapeutic targets for future treatments. 

Keynote Lecture 6 – Bence György, Institute of Molecular and Clinical Ophthalmology Basel 

Dr. Bence György discussed the potential of optogenetics - a gene therapy technique that introduces light-sensitive proteins into the retina - to restore some degree of vision in patients with advanced retinal degeneration. Early tests on human retinal tissue showed promising light responses, suggesting this approach could offer hope for vision restoration even when photoreceptors are largely lost. 

Keynote Lecture 7 – Aziz El-Amraoui, Université Paris Cité 

Dr. Aziz El-Amraoui presented work using mouse models of USH1B and USH1C to study disease origins, progression, and crucial clinical endpoints. His team is testing both single and dual AAV (adeno-associated virus) and minigene delivery strategies targeting these genes. Their aim is to broaden the therapeutic options available for different types of Usher syndrome. 

Keynote Lecture 8 – Maryna Ivanchenko, Department of Neurology, Harvard Medical School 

Dr. Maryna Ivanchenko shared encouraging preclinical progress in developing gene therapies for Usher syndrome type 1F. Her team’s work with dual AAV vectors and mini-PCDH15 constructs has shown promise in restoring function in experimental models of both the retina and inner ear, supporting the feasibility of gene therapy approaches for USH1F-related deafness and blindness. 

Keynote Lecture 9 – Katarina Stingl, Centre for Ophthalmology, University of Tübingen 

Prof. Katarina Stingl reflected on lessons learned from the Sepofarsen Phase 3 trial - a gene therapy trial for inherited retinal disease that was halted after not meeting its primary endpoints, despite showing some clinically meaningful visual improvements. She emphasised the importance of robust clinical trial design, highlighting that paired-eye studies, where one eye serves as a control for the other, may be particularly valuable in rare eye diseases to better detect true treatment effects. 

Keynote Lecture 10 – Jessie Hendricks and Ivonne Bressers, Department of Otorhinolaryngology, Radboud UMC

The final keynote of the symposium was a unique and moving joint presentation by Ivonne Bressers - patient advocate and founder of Stichting Ushersyndroom - and PhD candidate Jessie Hendricks. Ivonne shared her personal experiences living with Usher syndrome, particularly the often-overlooked challenges of sleep disturbances and severe fatigue. 

Jessie Hendricks presented her PhD research, which delved into why sleep problems are so common and so significant for many people with Usher syndrome. While it’s known that sensory impairments can cause fatigue due to the extra effort needed to navigate daily life, Hendricks’ findings suggest that Usher syndrome may also directly disrupt how the brain regulates sleep. This points to possible neurological impacts of Usher syndrome beyond vision, hearing, and balance. Although further studies are needed to confirm this theory, these early findings underline how much remains to be understood about the full spectrum of Usher syndrome’s effects on the body. 

Both speakers highlighted how crucial collaboration between researchers, patients, and patient organisations is in uncovering these insights and working toward improving quality of life for those living with Usher syndrome. 

Between the keynote lectures, eleven more fascinating abstract presentations covered diverse topics, including: 

• Myosin 7A regulates microbule organization and RPE cell division: Implications for Usher Syndrome Type 1 (Ivar Noordstra) 
• Decoding the Usher Proteome: Bridging 3D Structures and Exon-Skipping Therapeutics   (Hanka Venselaar) 
• Gene supplementation or activation for treatment of Usher syndrome 1B (Elvir Becirovic) 
• Skipping a frequently mutated exon in USH2A as therapeutic modality for USH2A-associated retinitis pigmentosa (Melita Kaltak) 
• From Cells to Cures - hiPSC-Derived Inner Ear Organoids and RNA Therapy to Resolve Genetic Hearing Loss (Winnie van den Boogaard) 
• Optimising transfection of non-viral USH2A gene therapy using  DNA lipid nanoparticles (Maria Toms) 
• Exploring exon-skipping as a therapeutic intervention strategy for the future treatment of ADGRV1-associated retinitis pigmentosa (Merel Stemerdink) 
• AAV-Mediated Exon Skipping Therapy for Usher Syndrome, Type 2A. (Stephanie Mauriac) 
• Drug development for USH1C: preclinical and clinical studies (Jennifer Lentz)
• A First-in-Human Phase I/II Trial of Dual AAV8.MYO7A, AAVB-081, Gene Therapy in Subjects with Usher syndrome Type 1B (USH1B) Retinitis Pigmentosa (Francesco Testa – LUCE)
• From Sound to Stability: Lessons learned from the CRUSH study on hearing loss progression and vestibular phenotype in Usher Syndrome type II (Dirk Wijn)

During the closing speech, the winner of the €300,000 Usher Crusher Grant by Stichting Ushersyndroom was announced. The award went to Prof. Marko Hawlina, MD, PhD, for his innovative project, AI-Driven Design of Mini-USH2A and Gene Electrotransfer for Mutation-Independent Therapy of Usher Syndrome Type 2.