MYELIN BASIC PROTEIN-LIKE MATERIAL--DELAYED MYELOGENESIS MONITOR

髓鞘碱性蛋白样物质--延迟髓细胞生成监测

• 批准号: 6241299
• 负责人: JOHN N WHITAKER
• 金额: $ 12.83万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6241299
• 关键词: biomarker; developmental neurobiology; developmental nutrition; disease /disorder proneness /risk; high performance liquid chromatography; human subject; infant human (0-1 year); longitudinal human study; low birth weight infant human; myelin basic proteins; myelination; myelinopathy; nervous system disorder diagnosis; noninvasive diagnosis; nutrition related tag; patient /disease registry; preschool child (1-5); radioimmunoassay; urinalysis; biomarker; developmental neurobiology; developmental nutrition; disease /disorder proneness /risk; high performance liquid chromatography; human subject; infant human (0-1 year); longitudinal human study; low birth weight infant human; myelin basic proteins; myelination; myelinopathy; nervous system disorder diagnosis; noninvasive diagnosis; nutrition related tag; patient /disease registry; preschool child (1-5); radioimmunoassay; urinalysis

This proposal rests on the hypothesis that the level of a urinary peptide which is immunoreactive with myelin basic protein (MBP) correlates with myelinogenesis and can provide a monitor of successful or failed myelinogenesis in children. The uncertain course, subclinical involvement and clinical and biological heterogeneity within the population of MR/DD patients render attempts at therapeutic or interventional trials based on clinical evaluation difficult, of long duration, and often inconclusive. To some extent, the problem represents an inability to assess injury or failed neurodevelopment adequately and accurately. This proposal represents a potentially powerful means of addressing this issue in a noninvasive manner and the advancing diagnostic and prognostic capabilities and monitoring the effectiveness of intervention strategies. The specific aims of this study are: (A) to document the normative developmental course of myelinogenesis in terms of the presence of MBPLM in urine from birth through 4 years of age (Study 1); (B) to determine in a very low birthweight (VLBW), less than 1000 gm, sample at high risk for peri-ventricular leukomalacia (PVL) and abnormal myelinogenesis, the presence of MBPLM at birth through 4 years of age (Study 2); (C) to conduct a longitudinal study of VLBW children from birth to 4 years of age to ascertain individual growth curves and to test for gender differences in MBPLM over time (Study 3); (D) to relate levels of MBPLM and their changes over time to clinical manifestations of MR/DD in the cross-sectional and longitudinal samples of VLBW children; (E) to characterize by high performance liquid chromatography (HPLC) the features of MBPLM at birth through 4 years; (F) to search for the presence of MBPLM encoded by exon 2 or MBP, expressed only during myelinogenesis; (G) to search for the presence of material cross-reactive with the citrullinated (C8) isomer of MBP, among the first charged isomers to appear during myelinogenesis; and (H) to acquire an archival clinical database on MBPLM levels in children (Study 4) with specific, relatively rare developmental disabilities associated with disorders of myelinogenesis, e.g. hypothyroidism, leukodystrophies, organic acid disorders, and amino acid disorders (including PKU). We recognize that the proposed studies are exploratory in terms of yielding meaningful information. However, reliable non-invasive markers of myelinogenesis re presently lacking. This recent methodologic breakthrough provides a unique opportunity to correlate neurodevelopmental characteristics in well-established and delineated cohorts with a marker of myelinogenesis. Thus, these studies have substantial potential for advancing knowledge about understanding normal and aberrant development.

该提议基于以下假设 与髓磷脂碱性蛋白（MBP）免疫反应性与 骨髓生成，可以提供成功或失败的监测器 儿童的脊髓衰变。 不确定的课程，亚临床 参与，临床和生物异质性 MR/DD患者的人群进行治疗或 基于临床评估的介入试验困难，长期很长 持续时间，通常没有定论。 在某种程度上，问题代表 无法充分评估伤害或失败的神经发育 准确。 该提议代表了一种潜在的强大手段 以无创的方式解决这个问题和前进 诊断和预后能力并监测有效性 干预策略。 这项研究的具体目的是：（a）记录规范 MBPLM的存在的骨髓生成的发育过程 从出生到4岁的尿液中（研究1）； （b）确定 在非常低的出生体重（VLBW）中，少于1000克，样本高风险 室周围白细胞（PVL）和异常脊髓纤维发生， 到4岁时出生时出生的MBPLM存在（研究2）； （c）到 从出生到4岁的VLBW儿童进行纵向研究 确定个体生长曲线并测试性别的年龄 随着时间的推移，MBPLM的差异（研究3）； （d）与MBPLM的水平相关联 它们随着时间的流逝而变为MR/DD的临床表现 VLBW儿童的横断面和纵向样本； （e）到 以高性能液相色谱（HPLC）为特征 MBPLM出生时至4年的特征； （f）搜索 由外显子2或MBP编码的MBPLM的存在，仅在 骨髓生成； （g）寻找材料交叉反应的存在 与MBP的Citrulladined（C8）ISOMER，在第一个充电中 异构体在骨髓生成过程中出现； （h）获取档案 关于儿童MBPLM水平的临床数据库（研究4）， 相对罕见的发育障碍与 脊髓衰变，例如甲状腺功能减退症，白细胞营养不良，有机酸 疾病和氨基酸疾病（包括PKU）。 我们认识到拟议的研究是探索性的 产生有意义的信息。 但是，可靠的非侵入标记 目前缺乏脊髓衰变。 这种最近的方法学 突破为关联提供了独特的机会 良好和划定的神经发育特征 与骨髓生成的标记。 因此，这些研究具有 促进有关理解正常知识的巨大潜力 和异常发展。