Enzymersatztherapien für lysosomale Speichererkrankungen

ZUSAMMENFASSUNG

Lysosomale Speichererkrankungen (LSDs) stellen eine Gruppe von > 70 Erkrankungen dar, die alle durch einen angeborenen Defekt der lysosomalen Funktion bedingt sind. Der klinische Verlauf ist durch Progredienz und Multiorganerkrankung mit u. a. Organomegalie, Skelettbeteiligung und z. T. Neurodegeneration charakterisiert.

Wichtigste Therapieoption der LSDs ist die Enzymersatztherapie (EET). Aktuell sind in Europa 17 Medikamente zur EET für 12 LSDs zugelassen. Langzeitdaten zeigen, dass die EET zu einer signifikanten Verbesserung einer Vielzahl von Krankheitsmanifestationen, der Lebensqualität sowie des Überlebens führt. Nebenwirkungen der EET sind v. a. immunologische Reaktionen, die zu allergischen Reaktionen oder zur Inaktivierung des infundierten Enzyms führen können. Nicht alle Organsysteme können durch die EET erreicht werden; hierzu zählt auch das zentrale Nervensystem, da die infundierten Enzyme nicht die Bluthirnschranke überwinden können.

Neue Präparate mit veränderter chemischer Struktur, die die erwähnten Limitationen der EET umgehen sollen, sind seit kurzem zugelassen oder noch in (prä)klinischer Entwicklung. Von ihnen ist eine weitere Verbesserung des Auskommens der Patient*innen mit LSDs zu erwarten.

ABSTRACT

Lysosomal storage disorders (LSDs) are a group of more than 70 different diseases, which are all caused by an inborn error of the lysosomal function. Clinical hallmarks are a progressive course of the disease and a multi-organ involvement with partly organomegaly, skeletal involvement and neurodegeneration in some of the patients.

Most important therapeutic option for LSDs is the enzyme replacement therapy (ERT). At the moment, 17 different drugs for ERT are approved in Europe for 12 different LSDs. Long-term data reveal a significant improvement of a multitude of organ manifestations, the outcome, and survival in patients with LSDs on ERT. Side effects of ERT include immunologic reactions, resulting in allergic reactions or inactivation of the infused enzyme. In addition, ERT does not reach all affected organ systems, especially it does not cross the blood brain barrier and thus, does not treat affections of the central nervous system.

New drugs with modified chemical structure are recently approved or in (pre)clinical testing. They address these problems and may result in a significant improvement of the outcome of patients with LSDs.

Schlüsselwörter

Lysosomale Speichererkrankungen - Enzymersatztherapie - Mannose-6-Phosphat-Rezeptor

Keywords

Lysosomal storage disorders - enzyme replacement therapy - mannose-6-phosphate receptor

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