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

马哮喘是一种世界性的马过敏性呼吸道疾病，由马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，因为抗炎药物如糖皮质激素只能减少临床症状。因此，研究新的治疗方法至关重要。通过吸入特异性细菌DNA序列（CpG-ODN）进行免疫调节治疗是一个很有前途的新途径，其通过特异性刺激免疫系统导致Th 1/Th 2漂移来下调过敏性免疫应答。CpG-OCN已成功用于人类哮喘研究的动物模型和过敏性鼻炎的临床试验（I期和IIa期研究）。明胶纳米颗粒作为一种分子转运系统，保护CpG-ODN不被泛素化核酸酶降解，同时也促进DNA分子进入免疫系统靶细胞的细胞摄取。在计划的研究项目中，将评估CpG-ODN吸入治疗炎症性气道疾病（IAD）的疗效。此外，我们的目的是比较的疗效相比，糖皮质激素吸入RAO和IAD（短期和长期的影响），研究可能的治疗效果的肺重塑的细胞外基质（基质金属蛋白酶及其组织抑制剂之间的失衡）和新的炎症标志物的过程中，可能发挥作用的马RAO和IAD下CpG-ODN吸入。

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.