Lactoferrin in Primate and Mouse Models of Asthma

灵长类动物和小鼠哮喘模型中的乳铁蛋白

• 批准号: 6743015
• 负责人: ATUL VARADHACHARY
• 金额: $ 9.99万
• 依托单位: AGENNIX, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-15 至 2004-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6743015
• 关键词: Primates; asthma; disease /disorder model; dosage; drug design /synthesis /production; drug screening /evaluation; interleukin 18; laboratory mouse; lactoferrin; nonhuman therapy evaluation; oral administration; pharmacokinetics; recombinant proteins; respiratory disorder chemotherapy; respiratory pharmacology

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.

描述（由申请人提供）：本研究的目的是扩大工作范围，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功效。哮喘是美国最流行的慢性炎症疾病之一，影响-15%的人口。尽管过去十年对哮喘进行了深入研究，但美国和发达国家的哮喘患病率、发病率和死亡率仍在持续上升。在美国，超过 1% 的医疗保健总费用用于治疗这种疾病。尽管进行了研究努力，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，但不幸的是并非对所有患者都有效。此外，皮质类固醇与许多潜在的不良副作用有关，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（一种天然存在的免疫刺激蛋白）被证明可以抑制哮喘特有的炎症。 Agennix 的新研究表明，口服乳铁蛋白还可以通过刺激 IL-18 的新机制有效治疗哮喘。 I1_-18 是一种有效的细胞因子，可能有助于改变导致哮喘相关炎症的 TH2 免疫反应。鉴于口服乳铁蛋白的强大安全性，乳铁蛋白有可能代表一种令人兴奋的、安全的、新颖的哮喘新疗法。这项研究将寻求 a.) 在绵羊身上确认早期结果，并在非人类灵长类动物模型中明确测试口服乳铁蛋白的功效，b.) 在灵长类动物中确定使用乳铁蛋白作为过敏原治疗的最佳剂量和方案。诱发哮喘症状，co) 进一步阐明 rhLF 在哮喘中的潜在作用机制，d.) 提供支持该适应症未来临床试验的证据。