Neue therapeutische Entwicklungen der Multiplen Sklerose

ZUSAMMENFASSUNG

Die Behandlungsmöglichkeiten der Multiplen Sklerose (MS) haben sich in den letzten 20 Jahren durch ein breites Arsenal von verlaufsmodifizierenden Immuntherapien massiv verbessert. Dies führt zunehmend zu einer Diskussion über eine Linksverschiebung des Therapiestarts bei Betroffenen mit einem ersten demyelinisierenden Herd im Rahmen eines radiologisch-isolierten Syndroms. Neue therapeutische Entwicklungen betreffen die Phase-III-Studienprogramme zu Inhibitoren der Bruton-Tyrosinkinase, die potenziell B-Zellen und myeloide Zellen im ZNS adressieren und deren weitere Ergebnisse im Jahr 2024 erwartet werden. Anti-CD20 gerichtete Antikörper erfahren u. a. durch die Entwicklung von „brain shuttles“ zur besseren Penetration des ZNS eine Evolution. Die Hemmung des kostimulatorischen CD40-Liganden Signalwegs wird mit Frexalimab in kürzlich begonnen Phase-III-Programmen untersucht. Außerdem werden zellbasierte Technologien aus der Onkologie mit der autologen hämatopoetischen Stammzelltransplantation (aHSCT) und innovativen Verfahren wie der chimeren Antigen-Rezeptor-(CAR-) T-Zelltherapie vorangetrieben. Diese Ansätze haben das Potenzial, bei therapierefraktären Verläufen unter hocheffektiven Therapien eingesetzt zu werden, befinden sich jedoch in einem sehr frühen Entwicklungsstadium. In dieser Übersichtsarbeit werden wir den aktuellen Stand der MS Therapiepipeline erörtern.

ABSTRACT

The treatment options for multiple sclerosis (MS) have improved substantially over the last 20 years thanks to a broad arsenal of disease-modifying immunotherapies. This leads to a discussion about shifting the start of therapy “to the left” in patients with a first demyelinating event in the context of a radiologically isolated syndrome. New therapeutic developments concern the phase 3 study programs about inhibitors of Bruton’s tyrosine kinase, which target B cells and myeloid cells in the CNS with study results expected in 2024. Anti-CD20-directed antibodies are experiencing an evolution due to the development of ‘brain shuttles’ for better penetration of the CNS, among other things. Inhibition of the co-stimulatory CD40 ligand signalling pathway is being investigated with frexalimab in recently initiated phase 3 programs. In addition, cell-based technologies from oncology are being advanced with autologous haematopoietic stem cell transplantation (aHSCT) and innovative procedures such as chimeric antigen receptor (CAR) T cell therapy. These approaches have the potential to be used in highly effective therapies for refractory disease but are at a very early stage of development. In this review, we will discuss the status of the MS therapy pipeline.

Schlüsselwörter

Multiple Sklerose - Immuntherapie - Bruton-Tyrosin-Kinase-Hemmer - CAR-T-Zelltherapie

Key words

Multiple sclerosis - immunotherapy - Bruton tyrosine kinase inhibition - CAR T cell therapy

Publication History

Article published online:
17 July 2024

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