Family organisations and the Foundation Fighting Blindness have published a new report on an initiative outlining a model for how affected individuals and their families can become research partners on the path to treatments and cures. The Foundation Fighting Blindness and the RDH12 family organizations reported an overall goal to bring together a group of patient representatives, clinicians, alongside with academic and industry researchers to discuss clinical trial readiness for treatments of RDH12-associated inherited disorders. RDH12-associated retinal dystrophy is one of the sub-types of Lever congenital amaurosis, referred to as LCA13. The disorder is a severe retinal dystrophy, with typical onset in the first years of life (2-4 years) and progression to legal blindness in early adulthood (18-25 years). At presently, there are no available treatments.
The recent workshop reported that specific objectives were highlighted to cover key areas including the knowledge about the RDH12-associated IRDs, specific challenges to the successful development of treatments, exploring key trial elements, trial design and regulatory issues implications, natural history studies, prioritization of a list of research questions and design of an opportunity roadmap with the ultimate goal of improving the probability of successful treatment development. The 27 participants of the workshop and report included academic centers, affected families, biotechnology and pharmaceutical companies, and the regulatory community. Several discussion topics focused on outcome measures and end-points, especially in the context of the recently successful approval for voretigene neparvovec-rzyl treatment (Luxturna) for RPE65-assiciated retinal dystrophy. Clinical trial design and natural history had a valuable roundtable discussion, in addition to concluding that 6-month nonclinical toxicology studies in at least two species would be sufficient before going on to an initial human safety study.
A number of key messages in their report summarised several priorities for future research and identified relevant gaps. Mouse models developed so far do not recapitulate the human RDH12 phenotype therefore, better models are needed to increase knowledge of the disease mechanisms in order to enable clinical translation. iPSCs and organoids were welcomed to support valuable pre-clinical testing of new therapeutic approaches. Gene therapy approaches provided the most promising opportunity, with a new clinical trial to be launched by the group led by Jean Bennet. Other pharmacological approaches to slow down cell degeneration were further supported including: neurotrophic factors, anti-apoptotic agents, antioxidant agents, and others. An RDH12 patient registry (the Foundation’s My Retina Tracker Registry) as well as biobanks and/or other accessible biorepositories for cell and animal models were all supported to foster research, increase knowledge of the disease and accelerate clinical translation. In concluding the study, the report outlined that “despite these research opportunities, the workshop participants agreed that the field could be ready now for a clinical trial aimed initially at testing the safety and, possibly, efficacy of RDH12 gene therapy. Advancements in this field are being fostered by the emergence of an innovative multi-stakeholder research endeavour that relies on the effective engagement of the patients”.