Pharmakotherapie von ABCA4-assoziierten Netzhautdystrophien

Zusammenfassung

ABCA4-assoziierte Netzhautdystrophien, einschließlich des von Stargardt erstmals beschriebenen Morbus Stargardt umfassen eine heterogene Gruppe erblicher Netzhauterkrankungen, die durch Mutationen im ABCA4-Gen verursacht werden und rezessiv vererbt werden. Diese Erkrankungen führen aufgrund einer fortschreitenden Degeneration von Photorezeptoren und retinalem Pigmentepithel zu einem Sehverlust, für den es aktuell keine zugelassene Therapie gibt. Aufgrund der Fortschritte in den letzten Jahren und der gut verstandenen Pathobiologie existieren bereits vielversprechende Therapieansätze in der klinischen Entwicklungsphase, wobei pharmakologische Ansätze zu den am weitesten fortgeschrittenen Therapieoptionen gehören. Präklinische und klinische Studien zeigen Fortschritte bei der Entwicklung von Medikamenten, die das Potenzial haben, die Progression dieser Erkrankungen deutlich zu verlangsamen. Darunter befinden sich Wirkstoffe, die die Lipofuszin-Akkumulation in der Netzhaut verringern können, die Bildung toxischer Vitamin-A-Dimere verlangsamen oder Lipofuszin aus der Netzhaut entfernen können. Weitere Substanzen greifen in den Vitamin-A-Stoffwechsel im Sehzyklus ein, indem sie die verfügbare Menge an Vitamin A im Auge reduzieren, was zu einer geringeren Bildung toxischer Stoffwechselnebenprodukte führen sollte. Dieser Beitrag fasst die der ABCA4-assoziierten Netzhautdegeneration zugrunde liegenden Pathophysiologie zusammen und erläutert aktuelle pharmakologische Therapieansätze.

Abstract

ABCA4-associated retinal dystrophies, including Stargardtʼs 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.

Schlüsselwörter

Genetik - ABCA4 - Morbus Stargardt - Netzhautdystrophie

Keywords

ABCA4 - inherited retinal disease - IRD - Stargardtʼs disease

Publication History

Received: 26 December 2024

Accepted: 29 January 2025

Article published online:
24 March 2025

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