Novel biomarkers for neuronal damage in multiple sclerosis

多发性硬化症神经元损伤的新型生物标志物

• 批准号: 7053269
• 负责人: Constance M John
• 金额: $ 17.48万
• 依托单位: CARANTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-15 至 2006-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7053269
• 关键词: antibody; biomarker; clinical research; multiple sclerosis; neurons; serum

DESCRIPTION (provided by applicant): The overall goal of the proposed research is to develop a clinical assay that can be used as a biomarker of neuronal damage and death in patients with multiple sclerosis (MS). Such an assay would aid in predicting the clinical course and pathological subtypes and would enable better treatment of individual patients. The research is relevant to the Clinical Immunology Branch of the Division of Allergy, Immunology, and Transplantation of the National Institute of Allergy and Infectious Disease (NIAID) that supports studies of the immune system in health and the cause, pathogenesis, diagnosis, prevention, and treatment of disease caused by immune dysfunction. The Phase I research is based on recent discoveries by Dr. Claude Genain and colleagues at the University of California, San Francisco. The specific aims of the Phase I research are as follows: Aim 1: To perform an extensive evaluation of anti-neuronal antibodies in serum and cerebrospinal fluid of patients with a clinically isolated syndrome, relapsing remitting or progressive MS, and correlate these measurements with clinical and MRI outcomes Aim 2: To identify the cellular targets for the destructive antibodies on human neurons. MS is a chronic disorder of central nervous system white matter affecting 350,000 Americans and over one million individuals worldwide. MS affects women twice as often as men, and thus also represents a significant women's health issue. This project is expected to result in development of a simple, fast, and reliable biomarker that can be used by clinicians to identify patients at risk to develop neuronal and axonal injury, in MS as well as other neurological disorders. This would enable physicians to utilize more effectively neuroprotective strategies that are in development, or already in use for patient subgroups (such as matrix metalloprotease inhibitors, statins, inhibitors of glutamate excitotoxicity, complement inhibitors, neurotrophins, and progenitor or stem cell approaches). In addition, the research could result in identification of novel targets for therapies using inhibitors of autoantibodies.

描述（由申请人提供）：拟议研究的总体目标是开发一种临床检测方法，可用作多发性硬化症（MS）患者神经元损伤和死亡的生物标志物。这样的测定将有助于预测临床过程和病理亚型，并且将能够更好地治疗个体患者。该研究与国家过敏和传染病研究所（NIAID）过敏，免疫学和移植部的临床免疫学分支有关，该分支支持健康免疫系统的研究以及免疫功能障碍引起的疾病的病因，发病机制，诊断，预防和治疗。第一阶段的研究是基于最近的发现，克劳德Genain博士和同事在加州大学，旧金山弗朗西斯科。I期研究的具体目的如下：目的1：对临床孤立综合征、复发缓解型或进展型MS患者的血清和脑脊液中的抗神经元抗体进行广泛评价，并将这些测量结果与临床和MRI结果相关联目的2：确定人类神经元上破坏性抗体的细胞靶点。MS是中枢神经系统白色物质的慢性疾病，影响35万美国人和全世界超过一百万人。多发性硬化症影响女性的频率是男性的两倍，因此也是一个重要的女性健康问题。该项目有望开发出一种简单、快速、可靠的生物标志物，可供临床医生用于识别MS和其他神经系统疾病中有神经元和轴突损伤风险的患者。这将使医生能够更有效地利用正在开发或已用于患者亚组的神经保护策略（如基质金属蛋白酶抑制剂、他汀类药物、谷氨酸兴奋毒性抑制剂、补体抑制剂、神经营养因子和祖细胞或干细胞方法）。此外，这项研究可能会导致识别使用自身抗体抑制剂的治疗新靶点。