Lactoferrin in Primate and Mouse Models of Asthma

描述(由申请人提供)：这项研究的目的是扩大工作，以确定口服重组人乳铁蛋白(RhLF)在已建立的灵长类哮喘模型中的疗效。哮喘是美国最常见的慢性炎症性疾病之一，影响着15%的人口。尽管在过去十年里对哮喘进行了密集的研究，但在美国和发达国家，哮喘的患病率、发病率和死亡率仍在继续上升。在美国，超过1%的总医疗费用用于治疗和治疗这种疾病。尽管进行了大量研究，但很少有新药被批准用于治疗哮喘。皮质类固醇和β-肾上腺素能激动剂仍然是主要的治疗方法，但不幸的是并不是对所有患者都有效。此外，皮质类固醇还与一些潜在的副作用有关，包括儿童生长迟缓、骨质疏松症、青光眼和白内障。因此，对于能够更有效、更安全地治疗这种疾病的新药，仍然存在大量未得到满足的医疗需求。在之前对绵羊哮喘模型的研究中，吸入乳铁蛋白，一种自然产生的免疫刺激蛋白，被证明可以抑制哮喘的炎症。Agennix的新研究表明，口服乳铁蛋白也可以通过刺激IL-18的新机制有效地治疗哮喘。I1-18是一种强大的细胞因子，可能有助于转移TH2免疫反应，从而导致与哮喘相关的炎症。鉴于口服乳铁蛋白的强大安全性，乳铁蛋白有可能成为一种令人兴奋、安全和新颖的哮喘新疗法。这项研究将寻求一种。)在绵羊身上证实早先的结果，并在非人类灵长类动物模型中明确测试口服乳铁蛋白的效果。在灵长类动物中确定使用乳铁蛋白治疗过敏原诱导的哮喘症状的最佳剂量和方案，co)进一步阐明重组人乳铁蛋白在哮喘中的潜在作用机制。提供证据支持这一适应症的未来临床试验。

DESCRIPTION (provided by applicant): The purpose of this research is to extend work to determine the efficacy of orally administered recombinant human lactoferrin (rhLF) in an established primate model of asthma. Asthma is one of the most prevalent chronic inflammatory diseases in the United States affecting -15% of the population. Despite intensive research on asthma over the past decade the prevalence, morbidity and mortality rates continue to increase in the U.S. and the developed world. Over 1% of total healthcare costs in the U.S. are directed towards the therapy and treatment of this disease. In spite of research efforts, few new drugs have been approved for the treatment of asthma. Corticosteroids and Beta-adrenergic Agonists remain the predominant therapies but unfortunately are not effective in all patients. In addition, corticosteroids are associated with a number of potential adverse side effects including growth retardation in children, osteoporosis, glaucoma and cataracts. There remains, therefore a large unmet medical need for new drugs that can more effectively and safely treat this disease. During a previous study in a sheep model of asthma, inhaled lactoferrin, a naturally occurring immuno-stimulatory protein, was shown to inhibit the inflammation which characterizes asthma. New research by Agennix indicates that orally administered lactoferrin is also effective in treating asthma through a novel mechanism involving the stimulation of IL-18. I1_-18 is a potent cytokine that may serve to shift the TH2 immune response responsible for the inflammation associated with asthma. Given the robust safety profile of orally administered lactoferrin there exists a possibility that lactoferrin may represent an exciting, safe and novel new therapy for asthma. This research will seek to a.) Confirm earlier results in sheep and definitively test the efficacy of orally administered lactoferrin in a non-human primate model, b.) Determine in primates the optimal dose and regimen for using lactoferrin as a treatment for allergen-induced asthma symptoms, co) Further elucidate the potential mechanisms of action of rhLF in asthma, d.) Provide evidence supporting future clinical trials in this indication.