Phase IIa trial of fingolimod for amyotrophic lateral sclerosis demonstrates acceptable acute safety and tolerability

被引：39

作者：

Berry, James D. ^{[1
,2
]}

Paganoni, Sabrina ^{[1
,2
]}

Atassi, Nazem ^{[1
,2
]}

Macklin, Eric A. ^{[1
,2
]}

Goyal, Namita ^{[3
]}

Rivner, Michael ^{[4
]}

Simpson, Ericka ^{[5
]}

Appel, Stanley ^{[5
]}

Grasso, Daniela L. ^{[1
]}

Mejia, Nicte I. ^{[1
]}

Mateen, Farrah ^{[1
]}

Gill, Alan ^{[6
]}

Vieira, Fernando ^{[6
]}

Tassinari, Valerie ^{[6
]}

Perrin, Steven ^{[6
]}

机构：

[1] Harvard Med Sch, Massachusetts Gen Hosp, Neurol Clin Res Inst, 165 Cambridge St,Suite 600, Boston, MA 02114 USA

[2] Harvard Med Sch, Dept Neurol, Boston, MA 02115 USA

[3] Univ Calif Irvine, Dept Neurol, Orange, CA 92668 USA

[4] Augusta Univ, Med Ctr, Dept Neurol, Augusta, GA USA

[5] Methodist Hosp, Dept Neurol, 6535 Fannin, Houston, TX 77030 USA

[6] ALS Therapy Dev Inst, Cambridge, MA USA

来源：

MUSCLE & NERVE | 2017年 / 56卷 / 06期

关键词：

circulating lymphocytes; clinical trial; FOXP3; neuroinflammation; RNA profiling; target engagement; REGULATORY T-LYMPHOCYTES; RELAPSING MULTIPLE-SCLEROSIS; MOUSE MODEL; ALS MICE; DISEASE PROGRESSION; ORAL FINGOLIMOD; ACTIVATION; MICROGLIA; SIGNATURE; SURVIVAL;

D O I：

10.1002/mus.25733

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

IntroductionImmune 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. MethodsRandomization 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. ResultsThirty 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). DiscussionFingolimod is safe and well-tolerated and can reduce circulating lymphocytes in ALS patients. Muscle Nerve56: 1077-1084, 2017

引用

页码：1077 / 1084

页数：8

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