Emerging gene therapy approaches under clinical investigation for retinal degenerative diseases

Abstract

Inherited retinal diseases (IRDs) have until recently not had prospects of effective treatment options. Preclinical studies have been very promising, but the number of clinical gene therapy trials has been very limited. The improved visual function outcomes in individuals affected by retinal dystrophy caused by biallelic variants in the RPE65 gene after gene therapy treatment contributed to the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval of the first gene therapy for any human inherited disease. This milestone in treatment for IRDs has greatly enhanced the development of new treatment trials. There are currently several active clinical trials for IRDs including retinitis pigmentosa, Leber congenital amaurosis, Stargardt disease, choroideremia, and achromatopsia. The area of optogenetics is an alternative approach where the remaining retinal neurons are converted into photosensitive cells. The majority of the current trials utilize a viral vector delivered into the subretinal space or into the vitreous cavity in order to express a specific gene. Other treatment options are targeting the mechanism of the retinal degeneration. This chapter is a review of the current gene therapy treatment clinical trials for IRDs, which may finally contribute to powerful treatment options for these progressive retinal dystrophies.