Teriflunomide and its mechanism of action in multiple sclerosis.
Teriflunomide and its mechanism of action in multiple sclerosis.
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DOI：
10.1007/s40265-014-0212-x
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发表时间：
2014-04
期刊：
影响因子：
11.5
通讯作者：
Wiendl, Heinz
中科院分区：
文献类型：
--
作者：
Bar-Or, Amit;Pachner, Andrew;Menguy-Vacheron, Francoise;Kaplan, Johanne;Wiendl, Heinz
多发性硬化症（MS）的治疗具有挑战性：疾病修饰治疗（dmt）必须既限制与疾病发生和传播相关的不必要的免疫反应（因为T和B淋巴细胞是复发性MS病理生理学中的关键细胞介质），又对正常的保护性免疫反应产生最小的不利影响。在这篇综述中，我们总结了与最近批准的DMT teriflunomide在ms中的作用机制相关的关键临床前和临床数据。teriflunomide选择性和可逆地抑制二氢旋氢酸脱氢酶（一种新的嘧啶合成途径中的关键线粒体酶），导致活化的T淋巴细胞和B淋巴细胞增殖减少而不引起细胞死亡。模拟与MS相关的免疫激活的动物实验结果表明，特立氟米特治疗可减轻疾病症状，同时减少中枢神经系统淋巴细胞浸润，减少轴突损失，并保留神经功能。与这些模型系统中获得的结果一致，泰瑞氟米特在MS患者中的3期临床试验一致表明，泰瑞氟米特提供了治疗益处，重要的是，不会引起临床免疫抑制。综上所述，这些数据证明了特立氟米特是如何作为多发性硬化症患者的一种选择性免疫疗法。
Treatment of multiple sclerosis (MS) is challenging: disease-modifying treatments (DMTs) must both limit unwanted immune responses associated with disease initiation and propagation (as T and B lymphocytes are critical cellular mediators in the pathophysiology of relapsing MS), and also have minimal adverse impact on normal protective immune responses. In this review, we summarize key preclinical and clinical data relating to the proposed mechanism of action of the recently approved DMT teriflunomide in MS. Teriflunomide selectively and reversibly inhibits dihydro-orotate dehydrogenase, a key mitochondrial enzyme in the de novo pyrimidine synthesis pathway, leading to a reduction in proliferation of activated T and B lymphocytes without causing cell death. Results from animal experiments modelling the immune activation implicated in MS demonstrate reductions in disease symptoms with teriflunomide treatment, accompanied by reduced central nervous system lymphocyte infiltration, reduced axonal loss, and preserved neurological functioning. In agreement with the results obtained in these model systems, phase 3 clinical trials of teriflunomide in patients with MS have consistently shown that teriflunomide provides a therapeutic benefit, and importantly, does not cause clinical immune suppression. Taken together, these data demonstrate how teriflunomide acts as a selective immune therapy for patients with MS.
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影响因子：
4.4
作者：
Bielekova, B;Sung, MH;Martin, R
通讯作者：
Martin, R
影响因子：
5.4
作者：
Archambault, AS;Sim, J;Russell, JH
通讯作者：
Russell, JH
影响因子：
3.7
作者：
Benkert TF;Dietz L;Hartmann EM;Leich E;Rosenwald A;Serfling E;Buttmann M;Berberich-Siebelt F
通讯作者：
Berberich-Siebelt F
DOI：
10.1084/jem.20111675
发表时间：
2012-05-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Barr TA;Shen P;Brown S;Lampropoulou V;Roch T;Lawrie S;Fan B;O'Connor RA;Anderton SM;Bar-Or A;Fillatreau S;Gray D
通讯作者：
Gray D
影响因子：
11.2
作者：
Bar-Or, Amit;Fawaz, Lama;Smith, Craig H.
通讯作者：
Smith, Craig H.