Inherited Retinal Diseases – natural history, disease modelling and gene therapies

Abstract

Evolving diagnostic technology have driven improvements in the molecular understanding of inherited retinal diseases (IRDs). This has also resulted in the ability to develop potential targeted genetic therapies with the aim of arresting further retinal degeneration. However, this requires significant pre-clinical development and testing in model systems such as animals or cell cultures.

Simultaneously, clinical trials for genetic therapies in IRD have resulted in mixed success, partly driven by clinical endpoints selection. For an investigational product to result in a potential therapy for patients it requires determination of potential biomarkers, often derived from natural history data. In addition, pre-clinical models aim to recapitulate similarities to human retina and further provide understanding of disease mechanism. Therapeutic design, testing and evidence of efficacy in model systems are an important step towards a clinical trial with the aim of an effective, safe therapy for patients. This work focused on the IRD gene PROM1, particularly the autosomal recessive (AR) form, with emphasis on all three aspects in the early stages of developing a potential genetic therapy.