Early Warning Systems for Childhood and Adult Disorders

儿童和成人疾病早期预警系统

基本信息

批准号：
10171850
负责人：
Manish Arora
金额：
$ 99.75万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2028-03-31
项目状态：
未结题

项目摘要

Project Summary According to the developmental origins of health and disease hypothesis, many disorders originate via environmental exposures in fetal and early postnatal life. Such early life environmental exposures can alter the developmental trajectory by disrupting the homeostasis of one or more systems, and in doing so produce identifiable biochemical signatures characteristic of the disease process or outcome. However, the lack of a conceptual framework as well as technological barriers have hampered research in this area; consequently, many disorders are not detected until overt clinical signs appear in adulthood, at which point it is no longer possible to meaningfully alter the course of development or disease. We are proposing a new paradigm that will overcome these barriers to detect disease years before current clinical and biochemical tests. By doing so we will be able to predict, and even prevent and treat diseases decades before any clinical signs. Central to our proposal is an underappreciated characteristic of many human physiologic processes—they commonly exhibit highly temporally resolved biochemical rhythms (or cycles) when at homeostasis. The idea of biochemical rhythms in itself is not revolutionary; sleep cycles, body temperature, cortisol rhythms, and menstrual cycles are all examples of the rhythmic nature of human physiology operating at various intervals. Medical testing, however, seldom considers rhythmicity. We propose to develop not just a novel technology that analyzes dynamic rhythmicity of key biochemical pathways during fetal development and childhood to accurately detect marked and sustained deviations from homeostasis that would be prognostic of later-life disease onset, but also a new framework for understanding development not solely as a linear trajectory but as interconnected rhythmic processes embedded within the growth trajectory.

项目摘要根据健康和疾病假设的发展起源，许多疾病起源于胎儿和早期产后生活中的环境暴露。这种早期生活环境暴露会改变通过破坏一个或多个系统的体内稳态来进行发展轨迹，并这样做疾病过程或结果的可识别生化特征。但是，缺乏概念框架以及技术障碍阻碍了该领域的研究；最后，直到成年后出现明显的临床体征，才发现许多疾病，此时不再有意义地改变发展或疾病的过程。我们提出了一个新的范式将在当前的临床和生化测试之前克服这些障碍以检测疾病几年。这样做在任何临床体征之前，我们将能够预测甚至预防和治疗数十年的疾病。中心我们的建议是许多人类生理过程的根本特征，它们通常在稳态时，表现出高度暂时解决的生化节奏（或周期）。这个想法生化节奏本身不是革命性的。睡眠周期，体温，皮质醇节奏和月经周期都是人类生理学的节奏性的例子。但是，医学测试很少考虑节奏。我们建议不仅开发一种新颖的技术这分析了胎儿发育和儿童期间关键生化途径的动态节奏性准确检测到的明显和持续的与稳态的偏离，这将是后期生活的预后疾病发作，也是理解发展的新框架，而不仅仅是线性轨迹，而是嵌入生长轨迹中的互连节奏过程。