Fiore Domenico
Viale Madonna delle Grazie, Piove di Sacco, Italia.
Am J Ther. 2007 Nov-Dec;14(6):555-60. doi: 10.1097/MJT.0b013e31804bfa6a.
Natalizumab (NTZ), defined as "the first of a new class of drugs known as elective adhesion molecule inhibitors" was developed at the beginning of 2003 to treat relapsing-remitting multiple sclerosis (MS) and was approved in the United States in November 2004. In February 2005, the production of NTZ was suspended by Producer Firms on account of the occurrence of two serious adverse events: two patients who had been taking NTZ manifested a progressive multifocal leukoencephalopathy; the patients showed progressive neurologic deterioration, initially believed to be a worsening of the pre-existing condition of MS. In March 2006, the Advisory Panel of the Food and Drug Administration voted unanimously in favor of the return of NTZ on the market with the majority of the panel also recommending that NTZ be considered the first choice of treatment in MS. NTZ should only be administered to patients who are not taking other medicines for MS and only in highly specialized centers. Inhibiting the adhesion of the circulating immune-competent cells to the vascular endothelium and reducing the precipitation of the circulating immune complexes (CICs) into the central nervous system, NTZ causes the level of the CICs to rise to values that inhibit the production of the antibodies (above all of the immunoglobulin Ms); because of the relative lack of antibodies, the pertussis toxins, no longer complexed, attack the nerve epithelia directly. We must conclude that 1) in remittent MS, between one attack and another (successive re-infection of bordetella pertussis) there are no CICs that can precipitate into the central nervous system, and thus the treatment with NTZ is useless and superfluous; 2) in chronic-progressive MS, the final result of the treatment with NTZ will be that of transforming MS into lateral amyotrophic sclerosis or progressive multifocal leukoencephalopathy; 3) in progressive MS, however, NTZ can be of considerable use in the first 2 months of antibiotic treatment to prevent the formation of new patches or the re-activation of previous ones. With the halt of toxin production (no bordetella pertussis strains resistant to erythrocyne exist) and continuing administration of the antibiotic on a long-term basis, there will be no further need of NTZ.
那他珠单抗（NTZ）被定义为“一类新型药物中的首个药物，即选择性黏附分子抑制剂”，于2003年初研发用于治疗复发缓解型多发性硬化症（MS），并于2004年11月在美国获批。2005年2月，生产厂家暂停了NTZ的生产，原因是发生了两起严重不良事件：两名服用NTZ的患者出现了进行性多灶性白质脑病；患者表现出进行性神经功能恶化，最初被认为是原有MS病情的加重。2006年3月，美国食品药品监督管理局咨询小组一致投票赞成NTZ重返市场，小组中的多数人还建议将NTZ视为MS治疗的首选药物。NTZ仅应给予未服用其他MS药物的患者，且仅在高度专业化的中心使用。NTZ通过抑制循环免疫活性细胞与血管内皮的黏附，并减少循环免疫复合物（CICs）在中枢神经系统中的沉积，导致CICs水平升高至抑制抗体（尤其是免疫球蛋白Ms）产生的值；由于抗体相对缺乏，百日咳毒素不再形成复合物，直接攻击神经上皮。我们必须得出以下结论：1）在缓解型MS中，在一次发作与另一次发作之间（百日咳博德特氏菌的连续再次感染），没有CICs能够沉积到中枢神经系统中，因此用NTZ治疗是无用且多余的；2）在慢性进展型MS中，用NTZ治疗的最终结果将是把MS转变为侧索肌萎缩性硬化症或进行性多灶性白质脑病；3）然而，在进展型MS中，NTZ在抗生素治疗的前两个月可用于预防新斑块的形成或先前斑块的重新激活。随着毒素产生的停止（不存在对红细胞有抗性的百日咳博德特氏菌菌株）以及长期持续使用抗生素，将不再需要NTZ。
