The Treatment of Multiple Sclerosis with Inosine
The Treatment of Multiple Sclerosis with Inosine
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DOI：
10.1089/acm.2008.0513
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发表时间：
2009-06-01
影响因子：
2.6
通讯作者：
Koprowski, Hilary
中科院分区：
文献类型：
--
作者：
Markowitz, Clyde E.;Spitsin, Sergei;Koprowski, Hilary
目的：本研究的目的是评估肌苷在复发缓解型多发性硬化症（RRMS）患者中的安全性和耐受性。次要目的是评估肌苷给药对血清尿酸（UA）水平、神经功能障碍进展、磁共振成像（MRI）上新的活动性病变累积数量以及炎症标志物血清水平变化的影响。设计：在一项为期1年的随机研究中，16名RRMS患者口服肌苷以提高血清天然过氧亚硝酸盐清除剂UA的水平，结果测量：研究的终点是复发率，残疾评估的Kurtzke扩展残疾状态量表（EDSS），MRI，和分析血清水平的硝基酪氨酸，氧化和促炎makers.Results：增加血清尿酸水平相关的钆增强病变和改善EDSS的数量显着减少。一些MRI强度为基础的参数改变肌苷治疗，在某些情况下与血清尿酸水平的变化。在低血清UA和高病变活动性的患者中，通过肌苷治疗提高UA水平降低了血清硝基酪氨酸，同时增加了循环细胞中Th 2与Th 1细胞因子的比例。与肌苷治疗相关的唯一副作用是肾结石形成4/16 subjects.Conclusions：这些数据表明，使用肌苷，以提高血清尿酸水平可能至少有一些MS患者的好处。这种治疗的效果很可能是过氧亚硝酸盐依赖性自由基失活的结果。需要密切监测血清UA水平以及其他措施，以避免肾结石的潜在发展。
Objective: The objective of this study is to evaluate the safety and tolerability of inosine in patients with relapsing-remitting multiple sclerosis (RRMS). The secondary objectives are to assess the effects of inosine administration on serum urate (UA) levels, the progression of neurologic disability, the cumulative number of new, active lesions on magnetic resonance imaging (MRI), and changes in serum levels for markers of inflammation.Design: Oral administration of inosine was used to raise serum levels of the natural peroxynitrite scavenger UA in 16 patients with RRMS during a 1-year randomized, double-blind trial.Outcome measures: The endpoints studied were relapse rate, disability assessed by the Kurtzke Expanded Disability Status Scale (EDSS), MRI, and analysis of serum levels of nitrotyrosine, and oxidative and proinflammatory makers.Results: Increased serum UA levels correlated with a significant decrease in the number of gadolinium-enhanced lesions and improved EDSS. A number of MRI intensity-based parameters were altered by inosine treatment, in certain cases correlating with changes in serum UA levels. In a patient with low serum UA and high lesion activity, raising UA levels by inosine treatment decreased serum nitrotyrosine while increasing the ratio of Th2 to Th1 cytokines in circulating cells. The only side-effect correlated with inosine treatment was kidney stone formation in 4/16 subjects.Conclusions: These data suggest that the use of inosine to raise serum UA levels may have benefits for at least some MS patients. The effect of this treatment is likely to be a consequence of inactivation of peroxynitrite-dependent free radicals. Close monitoring of serum UA levels as well as other measures are required to avoid the potential development of kidney stones.