Immunintervention bei neu diagnostiziertem Typ-1-Diabetes - immer noch nur im Rahmen von Studien möglich

Zusammenfassung

Der Erhalt einer körpereigenen Restproduktion von Insulin auch nach der klinischen Manifestation eines Typ-1-Diabetes (T1D) trägt wesentlich zu einer besseren Blutzuckereinstellung und zur Verhinderung diabetischer Folgeerkrankungen bei.

Diese Übersicht stellt Studien zur Immunintervention bei neumanifestem T1D dar. Primärer Endpunkt ist der Erhalt der Betazell-Reserve, gemessen am basalen und stimulierten C-Peptid. Sekundäre Endpunkte umfassen HbA_1c, Insulinbedarf, Nüchternblutzucker, sowie das zelluläre und humorale Immunmonitoring. 1) In München und Mailand werden derzeit im Rahmen des Verbundes Type 1 Diabetes TrialNet die aus der Transplantationsmedizin bekannten Stoffe Mycophenolat mofetil und Daclizumab (MMF-DZB) kombiniert. 2) In einer weiteren TrialNet-Studie soll, beginnend in diesem Jahr, mit Rituximab erstmals ein Wirkstoff bei T1D getestet werden, der B-Zellen depletiert. 3) In Belgien, Paris und München werden 80 Teilnehmer einer Phase II-Studie mit dem CD3-Antikörper ChAgly CD3 bereits im vierten Jahr nachbeobachtet. Ähnliche Studien sollen in Kürze folgen. 4) Die Wirksamkeit des synthetischen Peptids DiaPep277 wird derzeit in einer Phase III Studie an 400 Teilnehmern in elf Ländern verifiziert. 5) Eine Phase II Studie mit dem alterierten Peptidliganden APL-NBI-6024 zeigte keinen Effekt auf die Betazell-Restfunktion. 6) In München läuft eine Studie zur Immunintervention mit 1,25-Dihydroxy-Vitamin D3 mit 40 Teilnehmern.

Abstract

Even after clinical manifestation of type 1 diabetes (T1D), there is still residual secretion of endogenous insulin which essentially helps to maintain better metabolic control and to prevent complications.

This review describes intervention trials in newly diagnosed T1D. Primary endpoint is the preservation of the beta cell reserve, indicated by basal and stimulated C-peptide. Secondary endpoints include HbA_1c levels, insulin requirements, fasting blood glucose levels, and monitoring of cellular and humoral immune responses. 1) As a part of the Type 1 Diabetes TrialNet Network, a study performed in Munich and Milan combines mycophenolate mofetil and daclizumab (MMF-DZB). Both drugs are known from transplant medicine. 2) In another TrialNet study beginning this year, an agent depleting B-cells (rituximab) will be investigated in T1D for the first time. 3) In Belgium, Paris and Munich, 80 participants in a phase II study with the anti-CD3 antibody ChAgly CD3 have now been followed-up for nearly 4 years. Further studies with similar drugs have already been in preparation. 4) The effectiveness of the synthetic peptide DiaPep277 is being verified in a phase III study including 400 participants in 11 countries. 5) A phase II trial with the altered peptide ligand APL-NBI-6024 did not show any effect on betacell residual function. 6) In Munich, a trial tests the immunointervention with 1,25-dihydroxyvitamin D3 in 40 subjects.

Schlüsselwörter

Diabetes mellitus - Immunsuppression - Immunmodulation - Betazellfunktion - C-Peptid

Key words

Diabetes mellitus - immunosuppression - immunomodulation - beta cell function - C-peptide

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