We aim to develop a long-term efficient gene therapeutic approach modulating the complement system for treatment of inherited retinal dystrophies with genetics hard to be addressed by gene correction approaches.

Here we focus on Stargardt disease type 1 (STGD1) which affects children and young adults and is caused in most cases by mutations in the ATP binding cassette subfamily A member 4 (abca4) gene. Mice lacking the ABCA4 transporter (ABCA4-/- mice) are impaired in photoreceptor recycling and accumulate bisretinoids in the RPE, which activates the complement system. An overshooting complement system accelerates disease progression in patients suffering from Stargardt disease type 1 (STGD1). 

Given that enhanced complement activity is associated with many if not all forms of retinal degeneration, we would like to strengthen the point that our approach to dampen an overshooting complement activity could be a promising treatment option not only for STGD1, but for many other inherited retinal dystrophies - especially for those with unknown underlying genetics. Moreover, it could be worthwhile to test whether co-application of our complement modulatory approach with other gene therapeutic approaches prevents unwarranted inflammation caused by AAV application per se and thereby improves the overall outcome.