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）：这项研究的目的是扩展工作以确定在既定的哮喘灵长类动物模型中口服重组人乳铁蛋白（RHLF）的功效。哮喘是美国最普遍的慢性炎症性疾病之一，影响了-15％的人口。尽管对过去十年的哮喘进行了深入的研究，但美国和发达国家的发病率和死亡率仍在增加。在美国，超过1％的医疗保健费用用于治疗和治疗这种疾病。尽管进行了研究工作，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疗法，但不幸的是，在所有患者中都不有效。此外，皮质类固醇与许多潜在的不良副作用有关，包括儿童，骨质疏松症，青光眼和白内障的生长迟缓。仍然存在，因此，对新药的巨大未满足医疗需求，可以更有效，可以安全地治疗这种疾病。在先前的研究中，在哮喘的绵羊模型中，吸入乳铁蛋白（一种天然存在的免疫刺激蛋白）被证明可抑制表征哮喘的炎症。 Agennix的新研究表明，口服乳铁蛋白也可以通过涉及刺激IL-18的新机制来治疗哮喘。 I1_-18是一种有效的细胞因子，可以改变导致与哮喘相关的炎症的Th2免疫反应。鉴于口服乳铁蛋白的强大安全性，乳铁蛋白可能代表了一种令人兴奋，安全和新颖的哮喘新疗法。这项研究将寻求a。）确认较早的绵羊并确定测试口服乳铁蛋白在非人类灵长类动物模型中的疗效，b。）在灵长类动物中确定最佳剂量和方案，用于使用乳酸铁蛋白作为治疗方法，用于过敏原诱导的哮喘症状，以促进rhlf的临床效果。这个迹象。