Der Nervenarzt

, Volume 82, Issue 2, pp 215–225

Orales Fingolimod bei Multipler Sklerose

Therapeutische Modulation des Sphingosin-1-Phosphat-Systems
  • O. Aktas
  • J. Ingwersen
  • B. Kieseier
  • P. Küry
  • R. Hohlfeld
  • H.-P. Hartung
Aktuelles

Zusammenfassung

Fingolimod oder FTY720 ist die Leitsubstanz der kürzlich entdeckten Klasse von Sphingosin-1-Phosphat (S1P)-Rezeptor-Modulatoren mit außergewöhnlichen immunregulatorischen Eigenschaften. Mechanistische Studien in Tiermodellen der Multiplen Sklerose (MS) zeigen, dass Fingolimod den Austritt von Immunzellen aus sekundären lymphatischen Organen wie dem Lymphknoten unterbindet und damit die Lymphozytenmigration in entzündetes Zielgewebe verhindert. Tatsächlich belegt eine kürzlich publizierte Phase-III-Studie, dass täglich oral verabreichtes Fingolimod im Vergleich zu Placebo die entzündliche Krankheitsaktivität bei schubförmig-remittierender MS deutlich vermindert und den Verlauf der Erkrankung günstig beeinflusst. Eine weitere Phase-III-Vergleichsstudie zeigt, dass der therapeutische Effekt einer Standardtherapie mit intramuskulär appliziertem Interferon-β1a überlegen ist. Daher ist davon auszugehen, dass Fingolimod in naher Zukunft, möglicherweise zusammen mit Cladribin, als erstes orales Präparat in der MS-Therapie zur Verfügung stehen wird. Zudem legen neueste experimentelle Daten nahe, dass Fingolimod unabhängig von seinen immunmodulatorischen Eigenschaften auch neurale Reparaturmechanismen anstoßen könnte. In dieser Übersicht werden diese rezenten Erkenntnisse zusammengefasst, das immunologische und neurobiologische Profil von Fingolimod dargestellt sowie die vielsprechenden Daten der jüngst veröffentlichten klinischen Studien im Kontext des spezifischen Nebenwirkungsprofils erörtert.

Schlüsselwörter

Multiple Sklerose Fingolimod Sphingosin-1-Phosphat-Systems Therapie Multiple Sklerose Neurale Reparaturmechanismen 

Oral fingolimod in multiple sclerosis

Therapeutic modulation of the sphingosine-1-phosphate system

Summary

In this article the recent clinical data on novel therapy of relapsing multiple sclerosis with oral fingolimod (FTY720), lead substance of the recently described class of sphingosine-1-phosphate (S1P) receptor modulators are reviewed. Results of the two phase III studies (FREEDOMS; TRANSFORMS) corroborating previous phase II trial observations suggest that fingolimod has a strong anti-inflammatory effect in relapsing multiple sclerosis (MS), most probably by suppression of lymphocyte re-circulation from lymph nodes to inflammatory tissues (lymphocyte egress). Patients treated with fingolimod show a robust reduction of relapse frequency, compared to placebo (FREEDOMS) or an active comparator (interferon-β1a) (TRANSFORMS) and they show less inflammatory lesions on brain MR imaging. Furthermore, data from experimental research indicate that fingolimod may equally promote neural repair in vivo as well. Thus, the proposed immunological and neurobiological profile of fingolimod as well as the data from the recent clinical trials will be discussed in the context of the expected safety profile.

Keywords

Multiple sclerosis Fingolimod Sphingosine-1-phosphate system Therapy Neural repair mechanism 

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • O. Aktas
    • 1
  • J. Ingwersen
    • 1
  • B. Kieseier
    • 1
  • P. Küry
    • 1
  • R. Hohlfeld
    • 2
    • 3
  • H.-P. Hartung
    • 1
  1. 1.Neurologische UniversitätsklinikHeinrich-Heine-UniversitätDüsseldorfDeutschland
  2. 2.Institut für Klinische NeuroimmunologieLudwig-Maximilians-UniversitätMünchenDeutschland
  3. 3.Max-Planck-Institut für Neurologie, MartinsriedMünchenDeutschland

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