[Genetic therapies for Stargardt disease].

Stargardt disease is caused by biallelic variants in the ABCA4 gene and is the most frequent autosomal recessive macular degeneration in childhood and adolescence. No approved disease-modifying treatment has yet been approved. The size of the ABCA4 gene represents a challenge for conventional gene therapy based on adeno-associated viruses (AAV) and was the stimulus for the development of innovative strategies. Gene supplementation therapies use lentiviral or dual AAV vectors to introduce complete copies of the healthy ABCA4 gene into the target cells, whereas gene editing procedures, such as RNA exon editing or base editing, enable direct correction of the mutations causing the diseases. Intravitreal injection of antisense oligonucleotides selectively addresses splicing defects and provides a less invasive intravitreal approach but requires repeated applications. Indirect therapies modulate the visual cycle or neuroprotective signalling pathways and can be applied independent of variants. Finally, disease-agnostic approaches, such as optogenetics, enable restoration of vision in cases of advanced degeneration by the use of preserved inner retinal layers. The diversity of these approaches takes account of the broad spectrum of diseases that ranges from a disease limited to the macula to a generalized rod-cone dystrophy and perspectively opens up individualized treatment strategies depending on the genotype and phenotype.