Novel Complementary Therapy for Preterm Infants

早产儿的新型补充疗法

• 批准号: 7672028
• 负责人: John Anthony Bauer
• 金额: $ 18.52万
• 依托单位: NOVA-THER TECHNOLOGIES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7672028
• 关键词: Accounting; Animal Model; Animals; Apoptosis; Area; Biological Assay; Biology; Blood Chemical Analysis; Businesses; Cell Death; Cell Survival; Cells; Childhood; Complementary therapies; Consumption; DNA Damage; DNA Repair; Development; Disease; Dose; Enterocytes; Epithelial; Epithelial Cells; Future; Gatekeeping; Goals; Health; Healthcare Systems; Histopathology; Human; Incidence; Infant; Injury; Intestines; Investigation; Lead; Life; Live Birth; Marketing; Mediator of activation protein; Medical; Medicine; Methods; Modeling; Morbidity - disease rate; Morphology; Necrosis; Necrotizing Enterocolitis; Neonatal; Neonatal Intensive Care Units; Neonatology; Newborn Infant; Niacinamide; Nitric Oxide; Nitric Oxide Synthase; Operative Surgical Procedures; PARP inhibition; Pathogenesis; Pathway interactions; Perforation; Pharmaceutical Preparations; Pharmacology; Phase; Play; Poly(ADP-ribose) Polymerases; Population; Positioning Attribute; Pre-Clinical Model; Premature Birth; Premature Infant; Prevention; Proteins; Rattus; Reactive Nitrogen Species; Research; Research Personnel; Role; Route; Safety; Screening procedure; Secondary to; Signal Transduction; Small Business Technology Transfer Research; System; Technology; Testing; Therapeutic; Therapeutic Agents; Time; Tissues; Toxic effect; Treatment Protocols; United States; Very Low Birth Weight Infant; Villus; Work; attenuation; base; fetal; functional outcomes; high risk; improved; inhibitor/antagonist; innovation; medical specialties; mortality; neonatal human; novel; oxidation; pre-clinical; preclinical study; public health relevance; research and development; research study; response

DESCRIPTION (provided by applicant): Despite improvements in worldwide health and advances in medical practice the incidence of preterm birth continues to rise in virtually every region of the globe and is accounts for nearly 15% of all live births in the United States. Associated with this increased population of very low birth-weight infants are several medical conditions that are both life threatening and costly. One of these conditions is necrotizing enterocolitis (NEC), a major cause of morbidity and mortality in neonatal intensive care units, is a disease for which there is currently no medical treatment. An important feature of this application is the investigation of nicotinamide (known inhibitor of PARP) as a potential therapeutic agent for NEC. We will carry out preclinical studies to define mechanistic actions and identify optimal conditions for potential efficacy. These studies will use relevant human fetal intestinal epithelial cells and animal models of newborn intestinal injury to test our working hypothesis. Our Phase 1 aims are: AIM 1: Define concentration-effect relationships and signaling activities of Nicotinamide using a preclinical model of human neonatal enterocyte injury and restitution and AIM 2: Evaluate the safety of and dosing regimen for nicotinamide in our established rat model of NEC and demonstrate proof of principle for attenuation of intestinal injury in our established newborn rat model of NEC by Nicotinamide. The specific goal of this phase 1 project is to demonstrate the proof of principle for the use of nicotinamide for NEC prevention and/or treatment. PUBLIC HEALTH RELEVANCE: Despite improvements in worldwide health and advances in medical practice the incidence of preterm birth continues to rise in virtually every region of the globe and is accounts for nearly 15% of all live births in the United States. Associated with this increased population of very low birth-weight infants are several medical conditions that are both life threatening and costly. One of these conditions is necrotizing enterocolitis (NEC), a major cause of morbidity and mortality in neonatal intensive care units, is a disease for which there is currently no medical treatment. We have preliminary evidence to demonstrate that nicotinamide is a potential therapeutic agent for NEC. We will carry out preclinical studies to define mechanistic actions and identify optimal conditions for potential efficacy using relevant human fetal intestinal epithelial cells and animal models of newborn intestinal injury.

描述（由申请人提供）：尽管全球健康和医疗实践的进步有所改善，但早产的发生率几乎在全球每个地区都在上升，并且占美国所有活出生的近15％。与这种非常低的出生体重婴儿人群增加有关的几种医疗状况既威胁生命又昂贵。这些疾病之一是坏死性小肠结肠炎（NEC），这是新生儿重症监护病房发病和死亡率的主要原因，是目前尚无医学治疗的疾病。该应用的一个重要特征是研究烟酰胺（已知的PARP抑制剂）是NEC的潜在治疗剂。我们将进行临床前研究，以定义机械作用并确定潜在功效的最佳条件。这些研究将使用相关的人类胎儿肠上皮细胞和新生儿肠道损伤的动物模型来检验我们的工作假设。我们的第1阶段目标是：目标1：使用人类新生儿肠肠上的损伤和恢复原状的临床前模型来定义烟酰胺的浓度效应关系和信号传导活性。评估烟酰胺在我们既定的大鼠NEC模型中的烟酰胺和给药方案的安全性，并证明了我们在我们建立的Nort actin norn norn norn norn norn norn norn nort nort norn nort norn norn norn norn nort nort nort nort nort nort nort nort nort nort nort nort nort nort nort nort by nort nort nort nort sew nort bys的安全性。该阶段1项目的具体目标是证明使用烟酰胺进行NEC预防和/或治疗的原理证明。公共卫生相关性：尽管全球健康状况有所改善和医学实践的进步，但在全球每个地区，早产率的发生率仍在上升，并且占美国所有活出生的近15％。与这种非常低的出生体重婴儿人群增加有关的几种医疗状况既威胁生命又昂贵。这些疾病之一是坏死性小肠结肠炎（NEC），这是新生儿重症监护病房发病和死亡率的主要原因，是目前尚无医学治疗的疾病。我们有初步证明烟酰胺是NEC的潜在治疗剂。我们将使用相关的人类胎儿肠上皮细胞和新生儿肠道损伤的动物模型来定义机械作用并确定潜在疗效的最佳条件。