Identifying and Overcoming Challenges in Developing Effective Treatments for Usher 1B: A Workshop Report

PURPOSE: To identify challenges and opportunities for the development of treatments for Usher syndrome (USH) type 1B. METHODS: In September 2021, the Foundation Fighting Blindness hosted a virtual workshop of clinicians, academic and industry researchers, advocates, and affected individuals and their families to discuss the challenges and opportunities for USH1B treatment development. RESULTS: The workshop began with insights from individuals affected by USH1B. Presentation topics included myosin VIIA protein function in the ear and eye and its role in disease pathology; challenges with the USH1B mouse model most used in disease research to date; new investigations into alternative disease models that may provide closer analogues to USH1B in the human retina, including retinal organoids and large animal models; and learnings from and limitations of available disease natural history data. Participants discussed the need for an open dialogue between researchers and regulators to design USH1B clinical trials with appropriate outcome measures of vision improvement, along with multimodal imaging of the retina and other testing approaches that can help inform trial designs. The workshop concluded with presentations and a roundtable reviewing emerging treatments, including USH1B-targeted genetic augmentation therapy and gene-agnostic approaches. CONCLUSIONS: Initiatives like this workshop are important to foster all stakeholders in support of achieving the shared goal of treating and curing USH1B. TRANSLATIONAL RELEVANCE: Presentations and discussions focused on overcoming disease modeling and clinical trial design challenges to facilitate development, testing, and implementation of effective USH1B treatments.