MENTORED PATIENT-ORIENTED RESEARCH CAREER DEVELOPMENT AW

据估计，全世界有100万至125万人受到影响，北美有35万多人受到影响。疾病易感性似乎受到遗传决定因素、青春期居住地点以及可能接触某些传染物的年龄的影响。范德比尔特大学多发性硬化症实验室最近的工作发现了CNS感染与肺炎衣原体和多发性硬化症之间的联系。本应用程序的目的是检查抗生素治疗对多发性硬化症患者脑脊液（CSF）中肺炎衣原体感染的作用。我们假设适当的抗生素治疗将显著减少或根除MS患者脑脊液中的肺炎球菌感染，并且治疗后患者的临床病程将得到改善。一项随机临床试验将在肺炎梭菌阳性MS患者中进行为期6个月的时间，以检查两种不同抗生素方案与安慰剂的疗效。疗效将通过在培养系统中根除肺炎原体和使用定量聚合酶链反应（PCR）测定减少90%的DNA产物来确定。在发现有效的抗衣原体方案后，第二项随机临床试验将检查继发性进展性多发性硬化症（SPMS）患者队列的临床结果。这些患者中有一半将接受抗生素和干扰素治疗。1b，另一半是干扰素？1 b。这些患者将被随访两年，主要结果指标将是持续进展或残疾的指标。这些研究将确定多发性硬化症患者CNS肺炎球菌感染的最佳抗生素治疗方法，以及抗生素治疗是否会改变多发性硬化症的自然史。

It is estimated to affect between one million and one and a quarter million people worldwide and over 350,000 persons in North America. Disease susceptibility appears to be influenced by genetic determinants, location of residence through adolescence, and possibly age of exposure to certain infectious agents. Recent work in the MS laboratory at Vanderbilt University has found an association between CNS infection with Chlamydia pneumoniae and MS. The objectives of this application are to examine the role antibiotic therapy has on C. pneumoniae infection in the cerebrospinal fluid (CSF) of MS patients. We hypothesize that appropriate antibiotic therapy will markedly reduce or eradicate C. pneumoniae infection in the CSF of MS patients and that the clinical course of their disease will improve following treatment. A randomized clinical trial to examine the efficacy of two different antibiotic regimens versus placebo will be done over a six-month period of time in C. pneumoniae positive MS patients. Efficacy will be determined by eradication of C. pneumoniae in a culture system and a 90% reduction of DNA products using a quantitative polymerase chain reaction (PCR) assay. After an effective anti-chlamydial regimen has been found, a second randomized clinical trial will examine clinical outcome measures in a cohort of secondary progressive multiple sclerosis (SPMS) patients. Half of these patients will receive antibiotics and interferon-?1b and the other half interferon-?1b alone. These patients will be followed for two years and the primary outcome measure will be measures of sustained progression or disability. These studies will determine both the optimal antibiotic treatment of CNS C. pneumoniae infection in MS patients and if antibiotic therapy favorable alters the natural history of MS.