Treatment of Preterm Birth with ProstaglandinF2alpha Receptor Modulators

早产（PTB）是新生儿死亡的主要原因，也是儿童死亡的第二大原因。出生的儿童 早产儿往往有终身的健康问题，包括脑瘫，认知障碍，失明，耳聋，呼吸道疾病， 疾病和胃肠道疾病，以及慢性疾病，如高血压和血脂异常。住院费用 与PTB相关的疾病是最昂贵的：早产儿平均住院时间长11天， 与足月分娩相比，成本较高;妊娠28周前出生的新生儿成本较高（约100 000美元/婴儿）。在 尽管对与过早收缩有关的风险因素和机制有了更好的了解， 公共卫生预防计划，肺结核的发病率有所上升。PTB的经济影响使其成为最昂贵的 每位患者的医疗紧急情况。这些统计数字表明，发展 有效的治疗，可以延长妊娠，所谓的保胎剂。前列腺素-F2 α（PGF 2 α）启动 分娩，诱导分娩，并与小肽激素催产素互补，催产素通常用于 诱导人类分娩。为了开发一种新的宫缩抑制剂，我们靶向PGF 2 α受体（FP）， 两个具体的原因：1）FP表达在分娩的初始阶段增加，2）FP“敲除”小鼠不去 分娩，必须由剖腹产。通过创造一系列新的调节剂，包括基于肽的类似物， 在临床研究中证明是成功的，我们已经验证了FP作为一个可行的目标。这项研究旨在进一步 开发我们的原型，提供FP在分娩中的作用的基本知识，培训高素质的人才， 跨学科研究，并开发有效的治疗早产（PTL）的治疗方法，以提高出生后的生活质量 影响着整个生命。

Preterm birth (PTB) is the leading cause of newborn death and the second leading cause of child death. Children born preterm often have lifelong health issues, including cerebral palsy, cognitive impairement, blindness, deafness, respiratory illness and gastrointestinal disorders, as well as chronic diseases such as hypertension and dyslipidemia. Hospital costs associated with PTB are among the most expensive: premature babies remain hospitalized an average of 11 days longer at a higher cost compared to term births; newborns born prior to 28 weeks gestation incur major costs (~$100,000/infant). In spite of a better understanding of risk factors and mechanisms related to premature contractions, and the introduction of public health prevention programs, the rate of PTB has increased. The economic implications of PTB make it the most costly medical urgency per patient. These statistics demonstrate that significant savings could be obtained by the development of effective treatments, which can prolong gestation, so called tocolytic agents. Prostaglandin-F2alpha (PGF2alpha) initiates labour, induces childbirth, and works in compliment with the small peptide hormone oxytocin, which is commonly used to induce labor in humans. Towards the development of a new tocolytic agent, we targeted the PGF2alpha receptor (FP) for two specific reasons: 1) FP expression increases during the initial phase of parturition, and 2) FP ''knock-out'' mice do not go into labour and must be delivered by cesarian. By creating a series of novel modulators, including peptide-based analogs proving successful in clinical studies, we have validated FP as a viable target. The proposed research is designed to further develop our prototypes to provide basic knowledge of the role of FP in parturition, to train highly qualified personnel in interdisciplinary research, and to develop effective therapy to treat preterm labour (PTL) to enhance quality of life from birth which impacts throughout life.