Antagonist of Corticotrophin Releasing Hormone as Therapeutic Agents for the Prevention of Premature Birth In Humans

在发达国家，新生儿死亡的最常见原因是早产。在西方世界，早产仍然是新生儿死亡的最大原因，也是保健费用的主要消耗者。仅在美国每年就有50 - 70亿美元)。然而，将分娩时间从20周推迟到25周，可使婴儿存活率提高55%（每1000人死亡人数减少550人）。该项目将允许：开发可延长妊娠期的新药；制定可降低新生儿死亡率的方案。此外，我们相信这些新药物将有助于预防胎儿手术后分娩的发生。目前还没有有效的治疗方法能够大大改变分娩日期。现有的治疗方法最多可延迟分娩24小时。然而，我们实验室最近令人兴奋的结果表明，胎盘肽促肾上腺皮质激素释放激素（CRH）浓度的升高与分娩的开始有关。此外，我们还通过向绵羊胎儿中注入一种相对不溶性的CRH拮抗剂来延迟妊娠羊的分娩。只有在母亲停止服药后才开始分娩。该项目建立在一个跨学科团队的基础上：药物化学家、分子建模师、药理学家和内分泌学家，以进一步发展一项令人兴奋的澳大利亚发现。这项研究的成功完成将首次允许控制怀孕持续时间，最大限度地提高母亲和儿童的利益，降低通常与早产相关的死亡率和后期生活发病率。

In developed countries the most common cause of the death of a newborn baby is premature delivery. Pre-term delivery remains the greatest cause of neonatal mortality in the western world and a major consumer of health dollars (approx. $5-7B per year in the US alone). However, a delay in the onset of labour from 20 to 25 weeks has been shown to result in a 55% greater probability of infant survival (550 fewer deaths per 1000). This project will allow: The development of new drugs that will allow the extension of pregnancy term The development of protocols that will in turn reduce neonatal mortality. Additionally we believe that these new agents will be useful in preventing the onset of labour after fetal surgery. Currently there are no effective treatments capable of substantially changing delivery dates. Available therapeutics delay the onset of labour, at best, 24 hours. However, recent exciting results from our laboratories show that rising concentrations of the placental peptide Corticotrophin Releasing Hormone (CRH) are associated with the onset of labour. Further, we have also delayed the onset of labour in pregnant sheep by infusing a relatively insoluble CRH antagonist into the sheep fetus. Labour commenced ONLY AFTER the drug was withdrawn from the mother. This project builds upon an interdisciplinary team: medicinal chemists, molecular modellers, pharmacologists and endocrinologists, to further develop an exciting Australian discovery. Successful completeion of this research will, for the first time, allow the control of pregnancy duration MAXIMISING the benefits to mother and child, reducing mortality and later life morbidities typically associated with premature birth.