[Pharmacotherapy of ABCA4-associated Retinal Dystrophies]

Abstract

ABCA4-associated retinal dystrophies, including Stargardt's disease, comprise a heterogeneous group of inherited retinal diseases caused by mutations in the ABCA4 gene and are inherited in an autosomal recessive manner. These diseases cause vision loss due to progressive degeneration of photoreceptors and retinal pigment epithelium, for which there is currently no approved treatment available. Based on the progress made in recent years and the well-understood pathobiology, promising therapeutic approaches have reached the clinical development phase, with pharmacological approaches being among the most advanced therapeutic options. Preclinical and clinical studies show progress in the development of drugs that have the potential to slow the progression of these diseases. Among these are compounds that have the potential to reduce lipofuscin accumulation in the retina, slow the formation of toxic vitamin A dimers or remove lipofuscin from the retina. Other substances interfere with the vitamin A metabolism in the visual cycle by reducing the amount of available vitamin A in the eye, which should lead to lower formation of toxic metabolic by-products. This article summarises the underlying pathophysiology of ABCA4-associated retinal degeneration and provides an overview of current pharmacological treatment approaches.