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

马哮喘是一种世界范围内发生在马身上的过敏性呼吸道疾病，由吸入有机粉尘和霉菌引起，在许多方面与人类哮喘相似。这种常见的疾病仍然是一个治疗挑战，因为像糖皮质激素这样的抗炎药只会减少临床症状。因此，研究新的治疗方法是非常必要的。一种有前景的新疗法是通过吸入特异性细菌DNA序列(CpG-ODN)进行免疫调节治疗，它通过对免疫球蛋白系统的特异性刺激而下调过敏免疫反应，导致Th1/Th2-位移。CpG-OCN已成功地用于人类哮喘的动物模型研究和变应性鼻炎的临床试验(I期和IIa期研究)。明胶纳米粒作为一种分子运输系统，可以保护CpG-ODN不被普遍存在的核酸酶降解，还可以改善细胞对DNA分子进入免疫系统靶细胞的摄取。该方法已在马身上成功建立，并在Rao马身上得到了验证(I期和IIa期研究)。在计划的研究项目中，将评估CpG-ODN雾化吸入治疗炎症性呼吸道疾病(IAD)的疗效。此外，我们的目的是比较糖皮质激素在RAO和IAD中的疗效(短期和长期效果)，研究CpG-ODN对肺细胞外基质重塑(基质-金属蛋白酶及其组织抑制物之间的失衡)的可能治疗作用以及新的炎症标志物的进程，可能在CpG-ODN吸入下在马RAO和IAD中发挥作用。

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.