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）：尽管全球健康状况有所改善，医疗实践也取得了进步，但早产的发生率在地球仪的几乎每个地区都在持续上升，占美国所有活产婴儿的近15%。与极低出生体重儿人口增加相关的是几种危及生命和昂贵的医疗条件。这些病症之一是坏死性小肠结肠炎（NEC），其是新生儿重症监护病房中发病率和死亡率的主要原因，是目前没有医学治疗的疾病。本申请的一个重要特征是研究烟酰胺（已知的PARP抑制剂）作为NEC的潜在治疗剂。我们将进行临床前研究，以定义机制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胎儿肠上皮细胞和新生儿肠损伤的动物模型来验证我们的工作假设。我们的第一阶段目标是：目标1：使用人新生儿肠细胞损伤和恢复的临床前模型和AIM 2定义烟酰胺的浓度-效应关系和信号传导活性：在我们建立的NEC大鼠模型中评价烟酰胺的安全性和给药方案，并证明烟酰胺在我们建立的NEC新生大鼠模型中减轻肠损伤的原理证据。该I期项目的具体目标是证明烟酰胺用于NEC预防和/或治疗的原理证明。公共卫生关系：尽管世界范围内的健康状况有所改善，医疗实践也取得了进步，但早产的发生率在地球仪的几乎每个地区都在继续上升，并且占美国所有活产婴儿的近15%。与极低出生体重儿人口增加相关的是几种危及生命和昂贵的医疗条件。这些病症之一是坏死性小肠结肠炎（NEC），其是新生儿重症监护病房中发病率和死亡率的主要原因，是目前没有医学治疗的疾病。我们有初步证据表明，烟酰胺是一种潜在的治疗NEC的药物。我们将进行临床前研究，以确定机制作用，并确定使用相关的人胎儿肠上皮细胞和新生儿肠损伤的动物模型的潜在疗效的最佳条件。