Current and Future Directions in Developing Effective Treatments for PRPH2-Associated Retinal Diseases: A Workshop Report.

Abstract

A workshop of affected individuals and their families, clinicians, researchers, and industry representatives was convened in March 2023 to define the knowledge landscape of peripherin 2 (PRPH2) biology and identify challenges and opportunities towards developing PRPH2-associated inherited retinal disease (IRD) treatments. The results of an online survey and presentations from affected individuals and their family members revealed disease characteristics and impacts on daily living. Scientific sessions highlighted the significant heterogeneity in clinical presentation of PRPH2-related retinopathy; PRPH2's crucial function in rod and cone outer segment formation and maintenance; the usefulness of existing animal and cellular models for understanding disease pathophysiology; and possible therapeutic approaches for autosomal dominant PRPH2-associated IRDs, including gene-specific therapies and gene-agnostic approaches. Priority gaps identified by the workshop included having a more complete understanding of PRPH2's fundamental biology and factors contributing to PRPH2-related disease phenotypic diversity, establishing genotype-phenotype correlations, and creating additional models to probe the functional consequences of PRPH2 variants and to test therapies. Additionally, a natural history study involving a large number of participants is required to more fully characterize PRPH2-related disease progression, aiding in interventional clinical trial design. Because PRPH2-associated IRDs are rare, maximizing opportunities for communication and collaboration among stakeholders, such as that provided by the workshop, is crucial to overcome the challenges to developing effective treatments and improve the lives of affected individuals. Fostering communication among stakeholders to identify knowledge gaps, therapeutic challenges, and potential opportunities toward developing effective treatments for PRPH2-related IRDs.