Recombinant CC10 for treatment of meconium aspiration

重组 CC10 用于治疗胎便误吸

基本信息

批准号：
6645573
负责人：
APRILE L PILON
金额：
$ 10万
依托单位：
CLARAGEN, INC.
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-30 至 2005-03-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Recombinant human CC 10 is a novel therapeutic agent that is currently in clinical development for prevention of bronchopulmonary dysplasia (BPD) in preterm infants. CC10 is also known as clara cell secretory protein (CCSP) or uteroglobin and is produced primarily by tracheal and bronchial epithelia. The protein appears to have potent anti-inflammatory properties, one of which is inhibition of secretory phospholipase-2 (sPLA2). Several studies in CC10-deficient mice indicate that CC10 is very important in developing and maintaining normal lung function. Endogenous CC 10 is deficient in the lungs of preterm infants such that rhCC 10 is currently being administered as a replacement, analogous to exogenous surfactant in premature infants with respiratory distress syndrome (RDS). Other lung pathology may also be ameliorated by the introduction of rhCC10 into the lung. In term infants, the aspiration of meconium into the airway (either in utero or immediately after birth) causes acute lung injury, characterized by surfactant inactivation, atelectasis and pulmonary inflammation, sPLA2 is present in meconium and is thought to play a significant role in the pathogenesis of the injury process. While surfactant replacement therapy has been used in the treatment of meconium aspiration syndrome (MAS), often the pulmonary inflammatory response is so fulminant that this therapy is ineffective in treating the acute lung injury (possibly due to inactivation of the exogenous surfactant). Since rhCC 10 is an anti-inflammatory agent with known ability to inhibit sPLA2, we propose to verify the ability of rhCC 10 to inhibit sPLA2 activity in meconium (in vitro) and to test its efficacy in an animal model of MAS in newborn piglets (in vivo).

描述（由申请人提供）：重组人CC 10是一种新型治疗剂，目前正处于临床开发阶段，用于预防早产儿支气管肺发育不良（BPD）。 CC10 也称为克拉拉细胞分泌蛋白 (CCSP) 或子宫珠蛋白，主要由气管和支气管上皮产生。该蛋白质似乎具有有效的抗炎特性，其中之一是抑制分泌性磷脂酶 2 (sPLA2)。对 CC10 缺陷小鼠的多项研究表明，CC10 对于发育和维持正常肺功能非常重要。早产儿的肺部缺乏内源性 CC 10，因此目前正在使用 rhCC 10 作为替代品，类似于患有呼吸窘迫综合征 (RDS) 的早产儿的外源性表面活性剂。将 rhCC10 引入肺部也可以改善其他肺部病理学。在足月婴儿中，胎便吸入气道（在子宫内或出生后立即）会导致急性肺损伤，其特征是表面活性剂失活、肺不张和肺部炎症，sPLA2 存在于胎便中，被认为在损伤过程的发病机制。虽然表面活性剂替代疗法已用于治疗胎粪吸入综合征（MAS），但通常肺部炎症反应非常剧烈，以至于该疗法对治疗急性肺损伤无效（可能是由于外源性表面活性剂失活）。由于 rhCC 10 是一种已知能够抑制 sPLA2 的抗炎剂，因此我们建议验证 rhCC 10 在胎便中（体外）抑制 sPLA2 活性的能力，并在新生仔猪的 MAS 动物模型中测试其功效。体内）。