Preclinical Development of a Therapeutic Agent for COPD

描述(申请人提供)：粘液大量分泌到呼吸道，导致阻塞，增加发病率和死亡率，是几种肺部疾病的主要因素，包括慢性阻塞性肺疾病(COPD)、哮喘和囊性纤维化。目前还没有有效的治疗方法来控制这些疾病的过度粘液分泌。在之前发表的研究中，我们发现一种名为Marcks蛋白的特定蛋白质是粘液分泌途径中的关键分子。基于这一发现，发现了一种新的多肽，它能抑制培养的人呼吸道上皮细胞粘液的高分泌。 在SBIR第一阶段拨款的资助下，BioMarck制药公司延长了这些研究，并证实这种新型多肽在气管内滴注时是三种不同动物模型中粘液高分泌的有效抑制剂。这一发现可能会导致一种新的有效治疗方法，以抑制各种肺部疾病的过度粘液分泌。 在目前的SBIR第二阶段提案中，我们希望进一步开发这种多肽，以便支持向FDA申请IND(研究新药)，用于可能的人体志愿者临床研究。在这项建议中，该公司希望实现两个主要目标。也就是说，a)开发用于基于雾化器的肺部靶向给药的多肽的最佳配方，以及b)确定多肽在由雾化器给药到实验动物时的安全性。这一系列拟议的安全性研究是批准IND用于后续人类临床研究的先决条件。 BioMarck的目标是开发一种新型、有效和安全的治疗剂并将其商业化，以满足治疗粘液高分泌性疾病(如COPD)的医疗需求。COPD是美国和世界范围内的第四大死因。

DESCRIPTION (provided by applicant): Hypersecretion of mucus into the respiratory airways, leading to obstruction and increased morbidity and mortality, is a major factor in several lung diseases, including chronic obstructive pulmonary disease (COPD), asthma, and cystic fibrosis. There are presently no effective therapies to control excessive mucus secretion in these diseases. In previously published studies, we discovered that a specific protein called MARCKS protein is a key molecule in the mucus secretory pathway. Based on this finding, a novel peptide was discovered, which inhibited mucus hypersecretion in human airway epithelial cells in culture. With financial support from SBIR Phase I grant, BioMarck Pharmaceuticals has extended these studies and confirmed that this novel peptide is an effective inhibitor of mucus hypersecretion in three different animal models when instilled intratracheally. This discovery can potentially lead to a novel and effective therapy to inhibit excessive mucus secretion in a variety of pulmonary diseases. In the present SBIR Phase II proposal, we wish to further develop this peptide in order to support an IND (Investigational New Drug) application to the FDA for possible clinical studies in human volunteers. In this proposal, the Company wishes to accomplish two major objectives. Namely, a) to develop an optimum formulation of the peptide for nebulizer-based targeted lung delivery, and b) to establish the safety of the peptide when delivered by nebulizer to laboratory animals. The series of proposed safety studies are prerequisites for approval of an IND for subsequent human clinical studies. BioMarck's goal is to develop and commercialized a novel, effective, and safe therapeutic agent to satisfy the unmet medical needs for the treatment of mucus hypersecretory diseases like COPD, the 4th leading cause of death in the United States and worldwide.