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

促肾上腺皮质激素释放激素拮抗剂作为预防人类早产的治疗剂

• 批准号: nhmrc : 209853
• 负责人: Andreas Ruhmann
• 金额: $ 25.12万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2002
• 资助国家: 澳大利亚
• 起止时间: 2002-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/antagonist-corticotrophin-releasing-birth-humans/77131
• 关键词: Antagonist; Corticotrophin; Releasing; Hormone; Therapeutic

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 Labour commenced ONLY AFTER the drug was withdrawn from the mother.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.

在发达国家，新生儿死亡的最常见原因是早产。早产仍然是西方世界新生儿死亡的最大原因，也是医疗费用的主要消耗者（仅在美国每年就花费约 5-7B 美元）。然而，将分娩延迟 20 至 25 周已被证明可使婴儿存活率提高 55%（每 1000 人中死亡人数减少 550 人）。该项目将允许： 开发新药，以延长妊娠期限 制定方案，从而降低新生儿死亡率。此外，我们相信这些新药物将有助于预防胎儿手术后的临产。目前还没有能够显着改变分娩日期的有效治疗方法。可用的治疗方法最多可延迟 24 小时临产。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) 浓度的升高与临产的开始有关。此外，我们还通过向绵羊胎儿输注相对难溶的 CRH 拮抗剂，延迟了怀孕绵羊的临产时间。待母亲撤药后，分娩才开始。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，以进一步开发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，降低死亡率和通常与早产相关的晚年发病率。