Phase IIa trial of fingolimod for amyotrophic lateral sclerosis demonstrates acceptable acute safety and tolerability.
Phase IIa trial of fingolimod for amyotrophic lateral sclerosis demonstrates acceptable acute safety and tolerability.
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DOI：
10.1002/mus.25733
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发表时间：
2017-12
期刊：
影响因子：
3.4
通讯作者：
Perrin S
中科院分区：
文献类型：
--
作者：
Berry JD;Paganoni S;Atassi N;Macklin EA;Goyal N;Rivner M;Simpson E;Appel S;Grasso DL;Mejia NI;Mateen F;Gill A;Vieira F;Tassinari V;Perrin S
免疫激活与肌萎缩性侧索硬化症（ALS）的进展有关。口服fingolimod减少循环淋巴细胞。这项IIa期随机对照试验的目的是测试芬戈莫德治疗渐冻症的短期安全性、耐受性和靶向性。随机分组为2:1 （fingolimod：安慰剂）。治疗时间为4周。主要结局是安全性和耐受性。次要结局包括循环淋巴细胞和全血基因表达。随机选取30名参与者；28名患者服用药物（芬戈莫德18，安慰剂10）。未发生严重不良事件。治疗组的不良事件相似，中止研究也是如此（2例芬戈莫德vs 0例安慰剂，无统计学差异）。芬戈莫德组和安慰剂组1秒用力呼气量（FEV1）和FEV1/慢肺活量变化相似。芬戈莫德组循环淋巴细胞明显减少（P < 0.001）。9个免疫相关基因在fingolimod手臂中显著下调，包括forkhead box P3 （P < 0.001）和CD40配体（P = 0.003）。芬戈莫德安全且耐受性良好，可减少ALS患者的循环淋巴细胞。中国机械工程学报，2016,31 (2):444 - 444
Immune activation has been implicated in progression of amytrophic lateral sclerosis (ALS). Oral fingolimod reduces circulating lymphocytes. The objective of this phase IIa, randomized, controlled trial was to test the short‐term safety, tolerability, and target engagement of fingolimod in ALS. Randomization was 2:1 (fingolimod:placebo). Treatment duration was 4 weeks. Primary outcomes were safety and tolerability. Secondary outcomes included circulating lymphocytes and whole‐blood gene expression. Thirty participants were randomized; 28 were administered a drug (fingolimod 18, placebo 10). No serious adverse events occurred. Adverse events were similar by treatment arm, as was study discontinuation (2 fingolimod vs. 0 placebo, with no statistical difference). Forced expiratory volume in 1 second (FEV1) and FEV1/slow vital capacity changes were similar in the fingolimod and placebo arms. Circulating lymphocytes decreased significantly in the fingolimod arm (P < 0.001). Nine immune‐related genes were significantly downregulated in the fingolimod arm, including forkhead box P3 (P < 0.001) and CD40 ligand (P = 0.003). Fingolimod is safe and well‐tolerated and can reduce circulating lymphocytes in ALS patients. Muscle Nerve 56: 1077–1084, 2017
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DOI：
10.1093/brain/awr074
发表时间：
2011-05
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Beers DR;Henkel JS;Zhao W;Wang J;Huang A;Wen S;Liao B;Appel SH
通讯作者：
Appel SH
影响因子：
11.1
作者：
Henkel, Jenny S.;Beers, David R.;Wen, Shixiang;Rivera, Andreana L.;Toennis, Karen M.;Appel, Joan E.;Zhao, Weihua;Moore, Dan H.;Powell, Suzanne Z.;Appel, Stanley H.
通讯作者：
Appel, Stanley H.
影响因子：
9.9
作者：
Alexianu, ME;Kozovska, M;Appel, SH
通讯作者：
Appel, SH
影响因子：
--
作者：
APPEL, SH;STEWART, SS;BELENDIUK, GW
通讯作者：
BELENDIUK, GW
影响因子：
158.5
作者：
Cohen, Jeffrey A.;Barkhof, Frederik;Kappos, Ludwig
通讯作者：
Kappos, Ludwig