Pneumedoreductive Surfacant - New Therapy for Emphysema

描述（由申请人提供）：本I期SBIR申请由Bistech， Inc. of Woburn， MA提交。它将测试使用一种新的吸入药剂——气还性表面活性剂（PRS）治疗肺气肿的可行性。肺气肿是一种影响全世界数百万人的进行性致残疾病。现有的治疗肺气肿的药物，如支气管扩张剂和抗炎药物，疗效有限，因为它们不能解决肺气肿的基本生理缺陷：肺的胶原蛋白和弹性蛋白纤维被破坏导致的弹性后坐力丧失。两个因素决定肺弹性后坐力：1)组织纤维网络的拉伸和2)肺泡气液界面表面膜产生的表面张力。从理论上讲，通过修复组织纤维网络或增加表面张力可以恢复肺气肿的弹性后坐力。虽然医学疗法不能轻易地实现前者，但它们可能能够实现后者。Bistech开发了气还原性表面活性剂的原型配方。在初步的体外试验和短期体内试验中，这些配方似乎有效和安全地增加后坐力。本文提出的研究将扩展这些初步观察，并研究PRS是否可以用于临床试验。本提案的具体目的是评估在肺气肿实验模型中使用PRS的短期和长期生理和生物学反应，该模型准确地代表了人类的疾病。这些研究旨在提供关于PRS对体内肺功能影响的详细信息，并确定长期暴露于PRS的任何潜在毒性作用。如果I期成功，将提交II期申请，以完成临床前动物试验和产品配方，启动药理学-毒理学研究，制定生产计划，并开始计划在人类患者中进行1期临床试验。

DESCRIPTION (provided by applicant): This Phase I SBIR application is presented by Bistech, Inc. of Woburn, MA. It will test the feasibility of using a new inhaled pharmaceutical agent, pneumoreductive surfactant (PRS), to treat pulmonary emphysema, a progressive and disabling disease that affects millions of individuals throughout the world. Existing medical therapies for emphysema, such as bronchodilators and anti-inflammatory drugs, are of limited benefit since they do not address the fundamental physiological defect in this disease: loss of elastic recoil caused by destruction of the collagen and elastin fibers of the lung. Two factors determine lung elastic recoil: 1) stretching of the tissue fiber network and 2) surface tension generated by the surface film at the alveolar air-liquid interface. In, theory, elastic recoil could be restored in emphysema either by repairing the tissue fiber network or by increasing surface tension. While medical therapies cannot readily accomplish the former, they may be able to accomplish the latter. Prototype formulations of pneumoreductive surfactant have been developed by Bistech. In preliminary in vitro testing and short term in vivo testing, these formulations appear to increase recoil effectively and safely. The studies proposed here will extend these preliminary observations, and examine whether PRS can be developed for clinical testing. The specific aim of this proposal is to evaluate short and long term physiological and biological responses to PRS administration in an experimental model of emphysema that accurately represents the disease as it presents in humans. The studies are designed to provide detailed information about the effects of PRS on lung function in vivo, and to identify any potential toxic effects of prolonged PRS exposure. If Phase I proves successful, a Phase II application will be filed to complete preclinical animal testing and product formulation, initiate pharmacology-toxicology studies, develop a manufacturing plan, and begin the planning of a Phase 1 clinical trial in human patients.