Meininger V, Lacomblez L, Salachas F
Fédération de Neurologie Mazarin, Division Mazarin, Hôpital de la Salpêtrière, 47 boulevard de l'Hôpital 75013 Paris, France.
J Neurol. 2000 Dec;247:19-22.
Riluzole, after two significant trials, was introduced as the first standard treatment of amyotrophic lateral clerosis (ALS) in the early 95'. After 5 years what has changed in the field of ALS? In the field of basic science, riluzole as an active drug has largely contributed to stimulate the research of the possible role of glutamate in the genesis of ALS. However, the apparent simplicity of the relation between the drug and its mechanisms has to modulated in the light of the negativity of other trials (gabapentin) and the display of other mechanisms of the disease and of the compound. Possible relation with other putative mechanisms of ALS, as oxydative stress or growth factors, could be (and probably are) also involved. In the field of its activity, riluzole has an impact on the survival rate which has been largely debated. Comparison with historical databases are supporting the results of the two initial trials. Other information have been published supporting the probable activity of the drug on the muscle strength decline, a controversial matter. They strengthen the initial data and give additional reasons to use riluzole as a standard treatment of patients. In the field of the daily care, riluzole provided a real and unique hope for ALS sufferers. Even if its activity is not as complete as patients would have expected, it provides a hope for slowing down the rate of evolution and abolishes the myth of "no hope, no cure" which was the leitmotiv of patients care until recently. We have to better define the mode of administration with regard to the clinical status of the patients (respiratory disorders, fatigue, stiffness). In the field of care givers, riluzole was one major factor which provided the basis for national and international collaborations either for therapeutic trials or for standard of care. It made possible large collaborative programs in and among many countries. We do hope that this impulse will continue and be stimulated by additional results both in the field of basic science and clinical research.
经过两项重大试验后，利鲁唑在20世纪90年代初被引入作为肌萎缩侧索硬化症（ALS）的首个标准治疗药物。5年后，ALS领域发生了哪些变化？在基础科学领域，利鲁唑作为一种活性药物，在很大程度上推动了对谷氨酸在ALS发病机制中可能作用的研究。然而，鉴于其他试验（加巴喷丁）的阴性结果以及该疾病和化合物的其他机制的发现，药物与其作用机制之间表面上的简单关系必须加以调整。与ALS的其他假定机制，如氧化应激或生长因子之间的可能关系也可能（而且很可能）涉及其中。在其活性领域，利鲁唑对生存率有影响，这一点一直存在很大争议。与历史数据库的比较支持了最初两项试验的结果。其他信息也已发表，支持该药物对肌肉力量下降可能具有的活性，这是一个有争议的问题。这些信息强化了最初的数据，并为将利鲁唑用作患者的标准治疗提供了更多理由。在日常护理领域，利鲁唑为ALS患者带来了切实而独特的希望。即使其活性不如患者预期的那么理想，但它为减缓疾病进展速度带来了希望，并打破了“无希望、无治愈方法”的神话，而这一神话直到最近一直是患者护理的主导观念。我们必须根据患者的临床状况（呼吸障碍、疲劳、僵硬）更好地确定给药方式。在护理人员领域，利鲁唑是一个主要因素，为国内和国际在治疗试验或护理标准方面的合作提供了基础。它使得许多国家内部和之间能够开展大型合作项目。我们确实希望这一推动力能够持续，并受到基础科学和临床研究领域更多成果的激励。
