转自：医学界
从过去、现在到未来，看华山神内专家畅谈帕金森病的疾病修饰疗法~
帕金森病（PD）是一种常见的中老年神经系统退行性疾病，延缓或阻止PD神经退行性变的进程是帕金森病治疗领域的难题。疾病修饰疗法（DMT）是一种改变疾病自然病程的干预措施，可以影响神经元变性的初始触发因素，并促使神经元代偿反应或减少病理传播和进展。
那么，哪些药物可以用于PD的DMT，目前PD的DMT有何进展，未来又面临哪些挑战？今天这份来自华山神内专家的精彩讲解，大家一起看看！
PD修饰疗法的过去
过去的二三十年中，PD的药物治疗和手术治疗都取得了长足的进步。虽然PD的DMT裹足不前，但国内外学者进行了积极的探索，其中不乏有重要的研究成果。
DATATOP研究
DATATOP研究将800例未经治疗的早期PD患者随机分为司来吉兰+维生素E治疗组与安慰剂组，将需要进行左旋多巴治疗的时间设定为终点事件与主要结局指标。
结果发现，司来吉兰+维生素E治疗可以延迟左旋多巴使用9个月。但研究结果只能说明司来吉兰可以推迟了左旋多巴的使用时间，而左旋多巴的使用时间可能受到多种因素影响，因此DATATOP研究不能证实司来吉兰具有疾病修饰作用。
ELLDOPA研究
ELLDOPA研究是为验证左旋多巴对多巴胺神经元是否有毒性而设计的，研究纳入361名早期未经治疗的PD患者，随机分为4组：左旋多巴150、300、600 mg/d以及安慰剂组，用药40周后洗脱2周，观察洗脱前后疗效变化。
结果发现，使用左旋多巴各组的UPDRS运动评分恶化在洗脱期后仍小于安慰剂组，以左旋多巴600 mg/d组运动症状恶化最小。
ELLDOPA研究未能证实左旋多巴毒性，反而提示早期使用左旋多巴对PD患者无不良影响。但由于该研究影像学结果与临床研究结论相矛盾，因此，左旋多巴对多巴胺神经元是否有毒性作用或者能否修饰疾病进程尚难以下定论。
ADAGIO研究
ADAGIO研究纳入1176名未经治疗的PD患者，随机分为早期治疗组（接受剂量为每天1mg或2mg的雷沙吉兰治疗72周）和延迟治疗组（先安慰剂治疗36周，再每天使用1mg或2mg雷沙吉兰治疗36周）。
结果发现，1mg/d雷沙吉兰早期治疗组明显优于延迟治疗组，而2mg/d雷沙吉兰可能不具有疾病修饰作用。但该研究随访3年的结果提示，早期治疗与延迟治疗的UPDRS总分无显著性差异，因此雷沙吉兰的疾病修饰作用仍不能确定。
PD修饰疗法的现状如何？
哪些药物可以用于PD的DMT？
PD的DMT在未来将迎来哪些挑战？
机遇又在哪里？
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参考文献：
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