Neue Therapieansätze bei progredienter Multipler Sklerose

Die Therapie der Multiplen Sklerose hat sich in den letzten Jahren durch die Entwicklung neuer Medikamente für die schubförmige Phase der Erkrankung umfangreich gewandelt. Die Entwicklung von Medikamenten für Progression war bisher hingegen weniger erfolgreich. Neue Substanzen umfassen den in Europa und den USA zugelassenen B-Zell depletierenden Antikörper Ocrelizumab, der bei primär progredienter MS mit Krankheitsaktivität zugelassen ist, sowie den Sphingosin-1-Phosphat Modulator Siponimod, der aktuell in der Zulassungsphase für sekundär-chronisch progrediente MS ist. Progression ist durch chronische Inflammation mit Aktivierung von T- und B-Zellen sowie Mikroglia mit Freisetzung reaktiver Sauerstoffmetabolite, altersabhängige Akkumulation von Eisen und damit einhergehend neuronaler Degeneration gekennzeichnet. In dieser Arbeit soll eine Übersicht über das Verständnis der Pathogenese und vielversprechende Therapieansätze für Progression in unterschiedlichen Stadien der Entwicklung gegeben werden.

Multiple sclerosis (MS) therapy made huge progress during the last years due to the development of new medications for the relapsing-remitting phase of the disease. The development of therapies for progressive MS was, however, less successful. New medications are the B-cell depleting antibody ocrelizumab, authorized for primary progressive MS with inflammatory activity and the sphingosine-1-receptor modulator siponimod, which is under development for secondary-progressive MS. Pathomechanisms of progressive MS comprise chronic inflammation with activation of T and B cells and microglia with release of reactive oxygen species, age-dependent accumulation of iron and neurodegeneration. In this review, we will discuss the knowledge about the pathogenesis of progression and potential therapeutic approaches in different stages of development.

Schlüsselwörter:

neurologische Erkrankung - Medikamentenzulassung - Zentralnervensystem - Neurodegeneration

Keywords

neurological disease - drug approval - central nervous system - neurodegeneration

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