加拿大一个临床医学研究小组证明，由克里姆比尔神经医学中心迈克尔·泰米安斯基博士研发的一种神经保护剂药物可有效保护大脑减轻中风损伤效应。试验成果在线发表于近期《柳叶刀—神经病学》网站上，同时预测该中风药物成效的实验研究成果亦同步发表在《科学·转化医学》杂志上。
该项具有里程碑意义的临床试验，由卡尔加里大学霍奇基斯脑研所迈克尔·希尔博士领导，是一次随机、双盲、由加拿大和美国多个研究中心参与的试验。该研究评估了NA-1[Tat-NR2B9c]药物对曾接受神经介入治疗脑动脉瘤而引发轻微中风的患者的疗效。动脉瘤患者在接受此种介入治疗后，90%以上的患者会出现缺血性中风，但通常并不会引起明显的神经性伤残。
在试验中，受试者被随机抽取接受Tat-NR2B9c或安慰剂治疗。结果表明，接受Tat-NR2B9c治疗的患者，因脑动脉瘤修复术后造成的大脑损伤程度有所下降。该药物在脑动脉瘤破裂患者身上也取得了良好的临床试验效果。而在安慰剂对照组中，只有68%的患者取得了较好的效果。
希尔博士表示，为研发此类药物，人们此前已做过成千次的尝试，但最终均未能成功地将实验室里的成果转化到人体上。该临床试验成果是中风研究的一次飞跃。泰米安斯基博士认为，此次试验首次证明了，以提高大脑对中风抵御能力而设计的这种药物，在人体中展现了降低中风损伤效应的功效。此次临床试验也为血管性痴呆症等其他脑损伤的治疗提供了借鉴。
Safety and efficacy of NA-1 in patients with iatrogenic stroke after endovascular aneurysm repair (ENACT): a phase 2, randomised, double-blind, placebo-controlled trial
Prof Michael D Hill MD , Renee H Martin PhD , Prof David Mikulis MD , John H Wong MD , Prof Frank L Silver MD , Prof Karel G terBrugge MD , Prof Geneviève Milot MD , Prof Wayne M Clark MD , Prof R Loch MacDonald MD , Michael E Kelly MD , Melford Boulton MD , Ian Fleetwood MD , Prof Cameron McDougall MD , Thorsteinn Gunnarsson MD , Michael Chow MD , Cheemun Lum MD , Robert Dodd MD , Julien Poublanc MSc, Prof Timo Krings MD , Prof Andrew M Demchuk MD , Prof Mayank Goyal MD , Roberta Anderson PhD , Julie Bishop MA, David Garman PhD , Prof Michael Tymianski PhD , for the ENACT trial investigators
Background Neuroprotection with NA-1 (Tat-NR2B9c), an inhibitor of postsynaptic density-95 protein, has been shown in a primate model of stroke. We assessed whether NA-1 could reduce ischaemic brain damage in human beings.
Methods For this double-blind, randomised, controlled study, we enrolled patients aged 18 years or older who had a ruptured or unruptured intracranial aneurysm amenable to endovascular repair from 14 hospitals in Canada and the USA. We used a computer-generated randomisation sequence to allocate patients to receive an intravenous infusion of either NA-1 or saline control at the end of their endovascular procedure (1:1; stratified by site, age, and aneurysm status). Both patients and investigators were masked to treatment allocation. The primary outcome was safety and primary clinical outcomes were the number and volume of new ischaemic strokes defined by MRI at 12—95 h after infusion. We used a modified intention-to-treat (mITT) analysis. This trial is registered with ClinicalTrials.gov, number NCT00728182.
Findings Between Sept 16, 2008, and March 30, 2011, we randomly allocated 197 patients to treatment—12 individuals did not receive treatment because they were found to be ineligible after randomisation, so the mITT population consisted of 185 individuals, 92 in the NA-1 group and 93 in the placebo group. Two minor adverse events were adjudged to be associated with NA-1; no serious adverse events were attributable to NA-1. We recorded no difference between groups in the volume of lesions by either diffusion-weighted MRI (adjusted p value=0·120) or fluid-attenuated inversion recovery MRI (adjusted p value=0·236). Patients in the NA-1 group sustained fewer ischaemic infarcts than did patients in the placebo group, as gauged by diffusion-weighted MRI (adjusted incidence rate ratio 0·53, 95% CI 0·38—0·74) and fluid-attenuated inversion recovery MRI (0·59, 0·42—0·83).
Interpretation Our findings suggest that neuroprotection in human ischaemic stroke is possible and that it should be investigated in larger trials.
Funding NoNO Inc and Arbor Vita Corp.
