Fingolimod

Zusammenfassung

Prozesse der Signaltransduktion (Kommunikation von extra- nach intrazellulär) sind an einer Vielzahl physiologischer und pathologischer Prozesse beteiligt. Durch molekulare Analysen konnten in den vergangenen Jahren verschiedene Moleküle identifiziert werden, die zu neuen Therapiestrategien bei soliden und hämatologischen Tumoren geführt haben. Dieses Verständnis von Signaltransduktionskaskaden führte in vielen Bereichen zur Entwicklung neuer Wirksubstanzen, z. B. Fingolimod (FTY720), das bei der Therapie der Multiplen Sklerose erfolgreich in Phase-III-Studien getestet wurde. Fingolimod ist ein Sphingosin-1-Phosphatrezeptormodulator und ein funktioneller Antagonist von Sphingosin-1-Phosphat (S1P), welches über verschiedene G-Protein-gekoppelte Zellmembranrezeptoren an immunologischen, vaskulären und zellbiologischen Prozessen beteiligt ist. Im ZNS reguliert S1P unter anderem die Auswanderung von Lymphozyten aus dem Gefäßsystem und ist durch eine Förderung des Zellwachstums von Astrozyten an der Pathogenese neurodegenerativer Erkrankungen mit Astrogliose beteiligt. In diesem Übersichtsartikel sollen die molekularen und biochemischen Prozesse dargestellt und der Wirkmechanismus von Fingolimod in der Therapie der Multiplen Sklerose diskutiert werden.

Summary

Signal transduction processes (communication from extra- to intracellular compartments) are involved in a plethora of physiologic and pathologic processes. Molecular analyses identified a variety of molecules that have currently led to novel therapy strategies in solid and hematologic malignancies. This increased understanding of signal transduction cascades has now been applied successfully with Fingolimod (FTY720) in two phase III trials of multiple sclerosis. Fingolimod is a sphingosine-1-phosphate receptor-modulator and a functional antagonist of sphingosine-1-phosphate (S1P), which binds to different G-protein coupled transmembrane receptors and modulates immunologic, vascular and cell biologic processes. In the CNS, S1P also regulates the egress of lymphocytes from blood vessels and promotes proliferation of astrocytes, which is associated with the pathogenesis of neurodegenerative diseases with astrogliosis. In this article, the basic underlying molecular and biochemical processes of Fingolimod will be reviewed and the therapeutic effect in multiple sclerosis will be discussed.

Schlüsselwörter

Fingolimod - FTY720 - Sphingosinkinase 1 - Sphingosin-1-Phosphat - Signaltransduktionshemmung

Keywords

Fingolimod - FTY720 - sphingosinkinase 1 - sphingosine-1-Phosphate - signal transduction inhibition

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