BIOCHEMICAL STUDIES OF MYELINATION AND DEMYELINATION

我们建议研究三个密切相关的研究领域 关于新城疫的化学病理和免疫学基础 多发性硬化症脱髓鞘及其生化和遗传学基础 一种独特的小鼠髓鞘形成模型中髓鞘形成的研究。(1)主修 第一个领域的目标是提供有关该化学品的可靠数据 MS CNS组织的组成，特别是脊髓、脊髓髓鞘、 和斑块，并确定髓鞘破裂的生化基础 并进行修复。目前还没有针对MS的任何可靠的诊断程序。 我们已经开发了几种新的和高度敏感的程序来 分析许多与髓鞘相关的成分。这些程序是 专为个别患者提供的少量脑脊液而设计 并应有助于为活跃度提供客观可靠的指标 多发性硬化患者的脱髓鞘。(2)多发性硬化症的免疫学研究 内容广泛，但尚未回答有关病因学的重要问题， 诊断和治疗。然而，有强有力的证据表明， 自身免疫机制可能在该病的发病机制中起重要作用。 疾病。涉及髓鞘和髓鞘的自身抗原(S) 多发性硬化症少突胶质细胞变性的定义尚不清楚。我们可以的 通过以下方式更好地了解特定抗原的性质 在动物身上产生各种化合物的实验性疾病， 尤其是在中枢神经系统髓鞘中特异定位的化合物 和少突胶质细胞。此外，使用敏感的固相 用放射免疫分析方法检测人体内循环抗体 MS应该帮助回答关于这一性质的关键问题 自身抗原。(3)最后，我们计划在一个独特的 超髓鞘形成模型应该为我们提供更好的了解 甲状腺激素对髓鞘生成及髓鞘调节的影响 合成，以及控制髓鞘形成的遗传因素。一款应用程序 这项研究的目的当然是考虑应用的可能性 激素治疗以增强多发性硬化症患者的髓鞘再生过程。这个 从整个项目中获得的知识应该是改进 我们的诊断能力，在设计合理有效的治疗方法方面 MS，以及提供有关髓鞘发生和其 正常功能。

We propose to study three major areas of closely related research concerning the chemical pathology and the immunologic basis of demyelination in multiple sclerosis and the biochemical and genetic basis of myelinogenesis in a unique murine hypermyelination model. (1) A major goal of the first area is to furnish reliable data on the chemical composition of MS CNS tissues, especially that of spinal cord, cord myelin, and the plaques, and to define the biochemical basis of myeline breakdown and repair. There has not been any reliable diagnostic procedure for MS. We have developed several novel and highly sensitive procedures for analyzing a number of myelin-associated components. These procedures are designed for the small amounts of CSF available from individual patients and should be useful in providing objective and reliable indices for active demyelination in MS patients. (2) Immunological research in MS has been extensive but has not yet answered important questions regarding etiology, diagnosis and treatment. However, there is strong evidence that an autoimmune mechanism may play an important role in the pathogenesis of this disease. The autoantigen(s) that are involved in myelin and oligodendroglial degeneration in MS have not been clearly defined. We can gain a better understanding of the nature of the specific antigens by producing experimental disease in animals with various compounds, particularly the compounds that are specifically localized in CNS myelin and oligodendroglia. Additionally, the use of sensitive solid-phase radioimmunoassay procedures for the detection of circulating antibodies in MS should help answer the crucial question regarding the nature of the autoantigen. (3) Finally, our plan to study myelinogenesis in a unique hypermyelination model should provide us with a better understanding of the effect of thyroid hormone on myelinogenesis, the regulation of myelin synthesis, and the genetic factors governing myelination. An application of this study is, of course, to consider the possibility of applying hormonal therapy to enhance the remyelination process in MS patients. The knowledge obtained from the entire project should be essential in improving our diagnostic capability, in devising rational and effective therapies for MS, as well as in providing vital information on myelinogenesis and its normal function.