NP001 regulation of macrophage activation markers in ALS: a phase I clinical and biomarker study.
NP001 regulation of macrophage activation markers in ALS: a phase I clinical and biomarker study.
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DOI：
10.3109/21678421.2014.951940
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发表时间：
2014-12
影响因子：
2.8
通讯作者：
McGrath MS
中科院分区：
文献类型：
--
作者：
Miller RG;Zhang R;Block G;Katz J;Barohn R;Kasarskis E;Forshew D;Gopalakrishnan V;McGrath MS
这是一项在ALS患者中进行的NP 001的I期、安慰剂对照、单次给药剂量递增安全性和耐受性研究。NP 001是炎症巨噬细胞和单核细胞的新型调节剂。由于ALS进展被认为与神经炎症有关，因此该研究的另一个目的是评估NP 001施用对单核细胞活化标志物的影响。32名ALS患者入组并接受安慰剂（8名）或四种（每个剂量6名）递增单次静脉注射剂量（0.2、0.8、1.6和3.2 mg/kg NP 001）中的一种。监测患者的安全性，并在给药前和给药后24小时评估血液单核细胞免疫活化标志物CD 16和HLA-DR。计算较基线的变化。结果表明，NP 001总体上是安全的，耐受性良好。重要的是，单剂量的NP 001引起单核细胞CD 16（单核细胞活化/炎症的标志物）表达的剂量依赖性降低。此外，单核细胞HLA-DR表达在基线值升高的患者中也降低。总之，这些数据表明NP 001对ALS患者血液中的炎性单核细胞具有急性作用。在ALS疾病进展的背景下调节炎症的潜力需要进一步的长期随访研究。
This is a phase I, placebo-controlled, single ascending dose safety and tolerability study of NP001 in patients with ALS. NP001 is a novel regulator of inflammatory macrophages and monocytes. As ALS progression is thought to be related to neuroinflammation, an additional objective of the study was to assess the effects of NP001 administration on monocyte activation markers. Thirty-two ALS patients were enrolled and received either placebo (eight) or one of four (six at each dose) ascending single i.v. doses (0.2, 0.8, 1.6 and 3.2 mg/kg NP001). Patients were monitored for safety, and blood monocyte immune activation markers CD16 and HLA-DR were assessed pre- and 24 h post-dosing. Changes from baseline were calculated. Results showed that NP001 was generally safe and well tolerated. Importantly, a single dose of NP001 caused a dose-dependent reduction in expression of monocyte CD16, a marker of monocyte activation/inflammation. Additionally, monocyte HLA-DR expression was also decreased in those patients with elevated values at baseline. In conclusion, these data indicate that NP001 has an acute effect on inflammatory monocytes in ALS patient blood. The potential for modulation of inflammation in the context of ALS disease progression will require further study with long-term follow-up.
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影响因子：
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