Therapie des Typ-1-Diabetes im Wandel – Neue Möglichkeiten durch Immunintervention?

Zusammenfassung

Hintergrund: Der Typ-1-Diabetes zählt zu den Autoimmunerkrankungen. Ein Zusammenspiel von genetischen, immunologischen und zelltoxischen Faktoren führt zur Zerstörung der insulinproduzierenden Betazellen des Pankreas bei Menschen mit Typ-1-Diabetes. Eine Reihe von Immuntherapeutika befinden sich in Erprobung, um den natürlichen Verlauf der Typ-1-Diabeteserkrankung günstig zu beeinflussen. Methoden: Selektive Literaturrecherche in mehreren Datenbanken (Pubmed und clinicaltrials.gov, Stand: November 2010). Ergebnisse: Die heute in klinischen Studien verwendeten Immuntherapeutika zielen auf unterschiedliche Mechanismen der Immunabwehr wie der Antigenpräsentation (antigenspezifische Therapie, Rituximab), der Expansion autoreaktiver T-Zellen (anti-CD3) und der Inflammation durch Zytokine (IL-1β-Antagonist). Immuntherapeutika werden nicht nur nach Manifestation eines Typ-1-Diabetes adjuvant zu einer intensivierten Insulintherapie, sondern auch als Primärprävention bei Kindern mit sehr hohem Diabetesrisiko oder als Sekundärprävention bei Kindern, Jugendlichen und Erwachsenen mit positiven Inselautoantikörpern eingesetzt. Schlussfolgerungen: Adjuvante Immuntherapeutika und Kombinationen unterschiedlicher Substanzklassen könnten zur Verbesserung des Therapieerfolgs bei Typ-1-Diabetes in Zukunft eine große Rolle spielen. Wichtig wird auch die Bewertung der Sicherheitsprofile der Therapien sein, damit sie im Kindesalter oder auch zur Prävention vermehrt zum Einsatz kommen können. 

Abstract

Background: Type 1 diabetes is an autoimmune disease. An interaction of genetic, immunologic and cell-toxic factors leads to the destruction of insulin producing beta cells in the pancreas of patients with type 1 diabetes. A number of immune therapeutics which are to improve the natural progress of the disease are currently evaluated in clinical trials. Methods: Selective research of the literature in databases (pubmed and clinicaltrials.gov, November 2010). Results: Immune therapeutics used in current clinical trials target different mechanisms of the immune system, like antigen presentation (antigen specific therapy, Rituximab), expansion of auto reactive t-cells (anti-CD3), and inflammation via cytokines (IL-1β-antagonist). Immune therapeutics are not only applied after diabetes onset adjuvant to intensive insulin therapy, but also as primary prevention in children with a high diabetes risk or as secondary prevention in children, adolescent and adults with positive islet autoantibodies. Conclusion: Adjuvant immune therapeutics and combinations of different therapeutic principles may play an important role for future treatment of type 1 diabetes. The evaluation of drug safety will be crucial, so that therapies can be applied in early childhood or as preventive treatment. 

Typ-1-Diabetes - Immunintervention - Prävention

type 1 diabetes - immune intervention - prevention

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