Efficacy of inhalative gelatine nanoparticle bound CpG-ODN in horses affected by Inflammatory Airway Disease (IAD) and Recurrent Airway Obstruction (RAO)

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Equine asthma is a worldwide occuring allergic respiratory disease in horses caused by inhalation of organic dust and moulds resembling human asthma in many ways. This common disease is still a therapeutic challenge, as anti-inflammatory drugs like glucocorticoids only reduce the clinical signs. Therefore, research on new therapeutic approaches is essential. A promising new aporoach is immunmodulatory therapy by inhalation of specific bacterial DNA-sequences (CpG-ODN), which downregulates the allergic immune response by specific stimulation of the imme systeme leading to a Th1/Th2-Shift. CpG-OCN have been used successfully in animal models of human asthma research and in clinical trials on allergic rhinitis (phase I and IIa studies). Gelatine nanoparticles as a molecular transport system protect CpG-ODN of degradation by ubiquitious nucleases and also improve the cellular uptake of DNA molecules into target cells of the immune system.This method was established successfully in the horse and the efficacy has been proven in RAO horses (phase I and IIa studies). In the planned research project, the efficacy of CpG-ODN inhalation for the therapy of Inflammatory Airway Disease (IAD) is to be evaluated. Further, we aim to compare the efficacy in comparison to glucocorticoid inhalation in RAO and IAD (short and long-term effects), to study a possible therapeutic effect on pulmonary remodelling of the extracellular matrix (dysbalance between matrix-metalloproteinases and their tissue inhibitors) and the course of new inflammatory markers, possibly playing a role in equine RAO and IAD under CpG-ODN inhalation.