A Multicentre, Randomized, Double-blinded, Placebo-controlled, Parallel Group, Single-dose Design to Determine the Efficacy and Safety of Nerinetide in Participants With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy Excluding Thrombolysis

The primary purpose of this study is to determine if a single dose of nerinetide can reduce global disability in people who have had a stroke and are selected for endovascular therapy without the use of a tissue plasminogen activator (alteplase, tenecteplase, or equivalent).

开始日期2020-12-06

申办/合作机构

NoNO, Inc.

[+1]

NCT02930018

/ Completed临床3期

A Multicentre, Randomized, Double-blinded, Placebo-controlled, Parallel Group, Single-dose Design to Determine the Efficacy and Safety of Intravenous NA-1 in Subjects With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy

The ESCAPE-NA-1 study is designed to determine the safety and efficacy of the neuroprotectant, Nerinetide (NA-1), in reducing global disability in subjects with major acute ischemic stroke (AIS) with a small established infarct core and with good collateral circulation who are selected for endovascular revascularization.

开始日期2017-03-01

申办/合作机构

NoNO, Inc.

[+1]

NCT02056574

/ Withdrawn临床2期

Phase 2, Multicenter Randomized, Double-Blind, Placebo-Controlled, Safety and Efficacy Study Evaluating a Single Dose of Intravenous NA-1 in Patients With Subarachnoid Hemorrhage Undergoing Endovascular Repair of Ruptured Intracranial Aneurysms

This is a randomized, double-blind, placebo-controlled, single-dose study investigating the safety and efficacy of NA-1 in patients with subarachnoid hemorrhage (SAH) undergoing endovascular repair of ruptured intracranial aneurysms. Up to 300 male and female patients with SAH undergoing endovascular repair of a ruptured intracranial aneurysm will be dosed with 2.60 mg/kg of NA-1 or placebo as a 10 minute intravenous infusion after completion of the endovascular procedure on Day 1 of the study period. Subjects will undergo interim procedures at Day 2-4, Day 30-45, and end-of-study procedures on Day 90.

开始日期2015-11-01

申办/合作机构

NoNO, Inc.

100 项与 Nerinetide 相关的临床结果

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100 项与 Nerinetide 相关的转化医学

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100 项与 Nerinetide 相关的专利（医药）

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项与 Nerinetide 相关的文献（医药）

2026-01-01·INTERNATIONAL JOURNAL OF PHARMACEUTICS

Modifying the PSD-95 inhibitor NA-1 for brain delivery through proteolytic stabilization and conjugation to the potentially brain homing peptide BR1

Article

作者: Gammelgaard, Bente ; Brodin, Birger ; Andresen, Amalie Kjær ; Øie Solbak, Sara Marie ; Kristensen, Mie ; Kolberg, Hannah Grønbech ; Jensen, Camilla ; Thaysen, Maria

Delivering peptide-based therapeutics to the brain through systemic administration is limited by poor blood-brain barrier permeation, rapid proteolytic degradation, and off-target accumulation. The peptide NA-1, targeting PSD-95 interactions, holds promise for stroke treatment but suffers from these limitations. With this study, we explored whether complete D-amino acid substitution of NA-1 and conjugation to the potentially brain-homing peptide BR1 would improve NA-1 plasma stability and brain delivery, while retaining receptor binding and limiting off-target organ accumulation. Four peptide constructs, L- and D-versions of NA-1 and BR1-NA-1, were synthesized and characterized using circular dichroism spectroscopy, surface plasmon resonance, mouse plasma stability assays, cellular uptake studies, and biodistribution analysis in mice. D-amino acid substitution significantly enhanced peptide stability in plasma but compromised receptor binding and to some extent cellular uptake. L-BR1-NA-1 showed improved accumulation in whole brain lysates as compared to L-NA-1, however parenchymal delivery did not differ between the two peptides, indicating vascular retention of the L-BR1-NA-1 form. The present study demonstrated that substitution of L-amino acids with their D-amino acid counterparts improved the proteolytic stability of the constructs. However, this came at the expense of target affinity. BR1 conjugation to L-NA-1 might increase vascular retention, but did not increase parenchymal delivery, indicating that BR1 does not mediate transendothelial passage of the construct.

2025-12-01·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Development of cell-permeable and plasma-stable peptidomimetic inhibitors against PSD-95/nNOS interaction as potential anti-ischemic stroke agents

Article

作者: Qin, Yujiao ; Wang, Jiacheng ; Zhang, Lu ; Guo, Xiya ; Dong, Mingxin ; Ju, Han ; Liang, Ruiguo ; Zhou, Jie

The N-methyl-d-aspartate receptor (NMDAR)-neuronal nitric oxide synthase (nNOS)-postsynaptic density-95 (PSD-95) ternary complex represents a promising therapeutic target for acute ischemic stroke treatment. Although the shortest peptide ETAV targeting the PDZ2 domain of PSD-95 shows therapeutic potential, its limit in vivo stability restricts its broad application. Therefore, we herein systematically optimized and developed a series of novel peptidomimetics based on ETAV. We identified the optimal candidate compound 32-2, which displays potent neuroprotective effects in both HT22 cells (cell viability: 58.31 % at 10 μM) and primary cortical neurons (cell viability: 63.50 % at 20 μM). Mechanistically, 32-2 significantly reduced glutamate-induced intracellular ROS levels by 80 % compared to the glutamate-induced group, and modulated apoptotic markers (Bcl-2, Bax, cleaved-caspase 3). Furthermore, 32-2 exhibited potent plasma stability and excellent cellular permeability in vitro model. In the tMCAO model, 32-2 significantly reduced cerebral infarct volume compared to model group, being similar to NA-1. These findings establish 32-2 as the first effective peptidomimetic inhibitor of PSD-95 PDZ2 in vivo, offering a promising lead for developing novel stroke therapeutics.

2025-11-01·Brain and Behavior

Efficacy and Safety of Nerinetide in Acute Ischemic Stroke Patients: A Systematic Review, Meta‐Analysis and Meta Regression

Review

作者: Shams, Faizan ; Noor, Muaz ; Yousuf, Muhammad ; Somdev, FNU ; Samiullah, FNU ; Imran, Muhammad Junaid ; Malik, Waqar ; Chaulagain, Aayush ; Raja, Adarsh ; Khurram, Laiba ; Ubaid, Abdullah ; BS, Abdullah ; Ayalew, Biruk Demisse ; Kumar, Laksh ; Ji, Jodho

ABSTRACT:

Purpose:

Acute ischemic stroke (AIS) is a leading cause of disability and death worldwide. Nerinetide, a neuroprotective peptide, may limit ischemic brain injury. This systematic review and meta‐analysis evaluated the efficacy and safety of nerinetide versus placebo in patients with AIS.

Method:

Following the PRISMA and AMSTAR 2 guidelines, PubMed, MEDLINE, Cochrane Library, ScienceDirect, and ClinicalTrials.gov were searched until July 2025 for randomized controlled trials (RCTs) involving adult patients with AIS. The primary outcome was mortality, and secondary outcomes included functional recovery (modified Rankin Scale [mRS] scores of 0–1 and 0–2 and Barthel index scores of ≥95), infarct volume, and adverse events. Pooled risk ratios (RR) or mean differences (MD) were calculated using a random‐effects model, and meta‐regression was used to explore baseline moderators.

Findings:

Three RCTs ( n = 2462) were included in the analysis. Nerinetide showed a borderline significant mortality reduction versus placebo (RR = 0.86; 95% CI 0.75–1.00; p = 0.05) with low heterogeneity ( I2 = 11%). No significant differences were found in functional recovery or overall infarct volume, although subgroup analyses without reperfusion therapy suggested a possible benefit. The rates of adverse events, including serious events, thromboembolism, seizures, and hypotension, were similar between the groups. Meta‐regression indicated that atrial fibrillation ( p = 0.0489) and prior stroke ( p = 0.0519) were associated with a higher mortality risk.

Conclusion:

Nerinetide may modestly reduce mortality in AIS without increasing adverse events but does not significantly improve the functional outcomes. The benefits may be greater in patients who do not receive thrombolysis. Further large‐scale trials are warranted to clarify the optimal use and interactions with reperfusion therapies.

项与 Nerinetide 相关的新闻（医药）

2025-12-17

·医药观澜

2025年度盘点丨FDA再批准口服司美格鲁肽；口服PCSK9抑制剂关键3期结果积极……丨同行致远

编者按：多肽药物已成为治疗多种疾病的重要手段，拥有广阔的研发与临床应用前景。2025年以来，这类药物也在癌症、代谢性疾病、心血管疾病、罕见病等多个疾病治疗领域迎来一系列新进展，为患者带来新的治疗希望。为更好地满足全球合作伙伴在多肽药物研发方面的需求，药明康德旗下WuXi TIDES围绕多肽药物建立了一体化CRDMO平台，提供包括线性、环状和高度修饰的多肽，以及非天然氨基酸、连接子、毒素和多肽偶联物的合成服务，支持从药物发现、CMC开发到商业化生产的各个阶段。本文将回顾2025年多肽药物在心血管疾病领域取得的部分重要进展。近二十年来，多肽新药研发领域蓬勃发展。目前，全球已有约100款多肽药物获批上市，覆盖糖尿病、肥胖症、癌症及罕见疾病等多个领域，为患者带来了全新的治疗策略。与此同时，全球范围内还有上百项多肽类新药研发管线处于积极的临床研究阶段，适应症涉及癌症、代谢性疾病、心血管疾病、罕见病等多个疾病治疗领域。本文将回顾2025年多肽药物在心血管疾病领域取得的部分重要进展。 GLP-1类多肽疗法继续在心血管疾病适应症上取得新突破：比如：11月，学术期刊《柳叶刀》上发表了司美格鲁肽的一项3期临床试验SELECT的预设分析结果。结果显示，在不同基线体重和腰围水平的患者中，司美格鲁肽的心血管保护作用高度一致，未见异质性。该研究结果提示，中心性肥胖的减少可能有助于司美格鲁肽的心血管获益。同时，大部分心血管保护作用是通过独立于脂肪减少的其他机制实现的——研究者推测，其中的作用可能包括直接改善内皮功能、抗动脉粥样硬化、调节全身炎症反应、降低血压与血脂等。今年10月，诺和诺德（Novo Nordisk）宣布，美国FDA已批准Rybelsus（口服司美格鲁肽），用于降低2型糖尿病高风险成人患者发生重大不良心血管事件（MACE，即心血管死亡、心脏病发作或中风）的风险，无论其是否有既往心血管事件。根据新闻稿，此次获批使Rybelsus成为首款可降低2型糖尿病高风险成人患者MACE风险的口服GLP-1药物。8月，礼来（Eli Lilly and Company）也公布了其GIP/GLP-1双重受体激动剂Mounjaro（tirzepatide），在2型糖尿病合并动脉粥样硬化性心血管疾病成人患者中的疗效。与活性对照组相比，Mounjaro将心血管死亡、心梗或中风的风险降低了8%，达成非劣效性标准。除了GLP-1类多肽疗法，还有针对多种创新靶点的多肽新药在心血管疾病领域取得新进展，比如： 11月，默沙东（MSD）宣布在美国心脏协会（AHA）科学年会上首次公布了关键3期CORALreef Lipids和关键3期CORALreef HeFH的试验结果。研究表明，每日一次口服的在研PCSK9口服多肽抑制剂enlicitide decanoate有望帮助满足动脉粥样硬化性心血管疾病（ASCVD）及杂合子家族性高胆固醇血症(HeFH) 患者的未尽之需，以应对日益严峻的心血管疾病负担。其中，CORALreef HeFH研究结果已同步发表于《美国医学会杂志》(JAMA)。研究显示，治疗24周时，这款产品使HeFH成人患者的低密度脂蛋白胆固醇（LDL-C）水平较安慰剂显著降低了59.4%，达成主要终点。Enlicitide decanoate是一种与PCSK9结合并抑制PCSK9与LDL受体相互作用的大环肽，旨在通过与目前获批的注射型PCSK9抑制剂相同的生物学机制降低LDL-C，但以每日片剂形式给药。 7月，Corteria Pharmaceuticals宣布，基于积极的1期临床试验结果，正式启动其CRF2多肽激动剂COR-1167用于心力衰竭病情恶化患者的2期临床试验。1期数据显示，COR-1167在健康志愿者和慢性心力衰竭患者中总体安全且耐受性良好。单次给药后，能够明确激活促肾上腺皮质激素释放因子受体2（CRF2）靶点，改善多项心功能参数，且未对血压产生不良影响。CRF2是一种广泛表达于心血管、肾脏和代谢系统的质膜受体。在心衰患者和临床前心衰模型的概念验证研究中，CRF2激动剂可以发挥：改善心功能，减少肺充血、在标准护理的基础上促进利尿/钠尿等作用机制。 2月，医学期刊《柳叶刀》及其子刊《柳叶刀-神经学》连发3篇多肽药物nerinetide相关研究，从三篇研究的结果来看，症状发作后3小时内接受静脉溶栓和/或血管内血栓切除术的急性缺血性卒中患者或可从nerinetide治疗中获益，且未增加不良事件发生率。Nerinetide是一种用于急性缺血性卒中的神经保护药物，其可干扰突触后密度蛋白95（PSD-95），目前认为PSD-95蛋白-蛋白相互作用促发了脑缺血时的兴奋毒性细胞死亡。通过公开渠道梳理，全球范围内有数十项多肽疗法创新管线正在针对心血管系统疾病适应症开展临床研究。这些创新疗法的靶点涵盖GCG、GLP-1、GIP、C3、MC1R、PCSK9、AMYR、CTR、DLG4、NTRK2、CRHR2、FPR2、NPR1等等，适应症涉及高胆固醇血症、心力衰竭、急性缺血性卒中、高血压等等。除了上述进展，2025年以来还有其他多肽疗法在心血管疾病适应症领域迎来新进展，此处不再一一列举。一体化CRDMO平台赋能多肽疗法创新，加速惠及患者尽管前景可期，多肽药物在临床应用中仍面临诸多挑战，包括稳定性低、膜渗透性差，体内清除速度快、口服生物利用度有限等。因此需要对多肽骨架的化学修饰以及环化等策略来提升药物特征。同时，与传统小分子药物相比，多肽药物更为复杂，需要满足诸如非天然氨基酸合成、肽库合成、偶联化合物合成、放大生产工艺研发以及多肽制剂开发等方面的多种需求。为更好地满足全球合作伙伴在多肽药物研发方面的需求，药明康德旗下WuXi TIDES围绕多肽药物建立了一体化CRDMO平台，提供包括线性、环状和高度修饰的多肽，以及非天然氨基酸、连接子、毒素和多肽偶联物的合成服务，支持从药物发现、CMC开发到商业化生产的各个阶段。比如，WuXi TIDES多肽团队拥有丰富的复杂肽合成经验，在环化策略上，可采用多种策略合成双环肽和三环肽，包括单/双/三硫醚键环化、硫硫键环化、点击环化、内酯环化、内酰胺环化和烯烃复分解环化等；在合成能力上，具备N-烷基取代、骨架修饰、残基插入和非标准连接子合成等专业能力，有效支持多肽药物的结构活性探索。化学合成能力之外，WuXi TIDES还可赋能多肽药物从临床前到商业化阶段的口服和注射制剂的开发和生产。口服制剂平台支持包括片剂、胶囊、脂质体、粉末、颗粒和口服液等各类剂型的开发和生产；注射剂平台则支持多种剂型和灌装形式的无菌制剂生产。展望未来，药明康德将继续秉持“让天下没有难做的药，难治的病”的愿景，依托全球研发生产网络，凭借一体化、端到端CRDMO模式，持续助力全球合作伙伴充分发挥多肽疗法的潜力，为患者带来更多创新疗法。参考资料： [1]同行致远 | 精准抗癌的新模式！一体化平台助力多肽药物开发 | Bilingual.From https://mp.weixin.qq.com/s?__biz=MzAwMDA5NTIxNQ==&mid=2650115964&idx=1&sn=8ac868f5c6dcbcc1b6a9e8246e13765d&chksm=83ebb6f26e1cbdc02604aa85e60d634afd49262f79b5f07b9f3a560b5fc4edbaa97b87d532ed#rd 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医药观澜」微信公众号回复“转载”，获取转载须知。

临床3期AHA会议临床结果信使RNA

2025-12-05

·杨志华大夫

2025 年缺血性脑血管病研究与治疗热点

缺血性脑血管病作为全球致残、致死的主要病因之一，随着人口老龄化加剧和生活方式转变，疾病负担持续加重，成为公共卫生领域的重大挑战。2025年该领域研究聚焦于精准诊断技术革新、治疗策略优化及病理机制深度解析，从急性缺血性卒中溶栓治疗实践与全域研究热点视角，呈现了该领域的最新进展与发展趋势。一、精准诊断技术：从影像引导到多维度整合精准诊断是缺血性脑血管病个体化治疗的前提，2025年相关研究以 “技术融合” 为核心特征，实现了从早期识别到预后评估的全流程优化。在影像诊断方面，多模态影像技术与人工智能（AI）的结合成为关键突破。MRI、CT 灌注成像及 PET 技术的协同应用，能够精准勾勒缺血病灶范围、评估血流动力学及代谢功能，为溶栓治疗筛选提供核心依据。例如 WAKE-UP 研究采用 MRI 引导发病时间未知的卒中溶栓，EXTEND 研究通过灌注成像将溶栓时间窗扩展至发病后 9 小时，均证实了影像技术在突破传统时间窗限制中的核心作用。AI 辅助影像分析进一步提升了诊断效率与准确性，通过深度学习算法实现微小病灶识别、自动化数据处理及三维重建，减少人为误差，为快速决策提供支持。血液生物标志物与多组学技术的应用丰富了诊断维度。神经元特异性烯醇化酶（NSE）、脑源性神经营养因子（BDNF）等标志物可早期反映神经元损伤，炎症因子与氧化应激相关分子则揭示疾病免疫代谢异常。基因组学、蛋白质组学与代谢组学的整合分析，构建了多维度生物标志物谱，结合影像学数据形成的联合诊断模型，显著提升了疾病分型与风险预测的精准度。数字健康技术拓展了诊断与监测边界。可穿戴设备实现心率、血压等生命体征的连续监测与远程传输，移动健康应用通过智能提醒与行为指导强化患者管理，远程神经认知评估工具则为康复效果监测提供了便捷手段，推动诊疗模式向 “智能化、精细化” 转型。二、治疗策略优化：溶栓突破与多手段协同 2025 年缺血性脑血管病治疗以 “扩宽适用范围、提升疗效、降低风险” 为核心，在溶栓治疗优化、神经保护创新及再生医学应用等方面取得显著进展。（一）溶栓治疗：时间窗拓展与特殊人群适配传统 4.5小时溶栓时间窗被持续突破，基于影像筛选的个体化溶栓成为主流策略。EXTEND 研究证实，发病 4.5-9小时内符合 “低灌注与梗死核心体积比> 1.2、缺血核心 < 70ml” 错配标准的患者，阿替普酶溶栓可显著改善功能结局（35.4% vs 对照组 29.5%）；TRACE-3研究进一步将时间窗延伸至 4.5-24 小时，针对前循环大血管闭塞患者，替奈普酶（TNK）溶栓使 90 天良好功能结局比例提升至 33%（对照组 24.2%），为晚期溶栓提供了新证据。特殊人群的溶栓适应症不断放宽。研究证实 80 岁以上高龄患者接受阿替普酶溶栓的有效性与年轻患者相似，症状性颅内出血风险与年龄无关；卒中前合并痴呆或残疾、轻型卒中及症状快速缓解、脑内少量微出血（<10 个）或脑白质高信号患者，在充分评估沟通后可获益于溶栓治疗；儿童大血管闭塞卒中患者（发病 4.5 小时内），经专家评估后也可采用再灌注治疗。此外，癫痫发作、颅外颈部动脉夹层、未破裂小动脉瘤（<10mm）等特殊情况，不再作为溶栓绝对禁忌，个体化风险 - 获益评估成为决策核心。溶栓药物与方案持续优化。TEMPO-2 研究对比了发病 12 小时内轻型卒中患者的 TNK 溶栓与常规治疗，虽主要疗效终点未达显著差异，但为轻型卒中的干预提供了参考；CHABIS-H 研究聚焦中国人群大 / 中型血管闭塞患者，探索 TNK 在 4.5-24 小时时间窗内的应用，以 “完全血管再通 + 无 symptomatic 颅内出血（sICH）” 为核心终点，为亚裔人群的个体化治疗提供依据。（二）神经保护与再灌注损伤防控多靶点神经保护药物研发成为热点。针对氧化应激、炎症反应及焦亡机制的药物取得进展，如含钆的层状双氢氧化物纳米片（AFGd-LDH）结合阿托伐他汀，氧自由基清除能力达 90%，显著优于临床药物依达拉奉；铁死亡抑制剂与纳米酶协同作用可减轻神经炎症与细胞死亡。多靶点联合用药策略也得到探索，nerinetide、依达拉奉等与溶栓 / 取栓联合应用，显示出改善功能预后的潜力；GLP-1 类似物通过抗凋亡作用减少梗死面积，为缺血再灌注损伤提供了新的药物方向。非药物神经保护手段逐步推广。体表感觉皮层电刺激通过激活 BDNF/PI3K/Akt/mTOR 信号通路抑制炎症与凋亡，远程缺血预处理则通过调控机体应激反应减轻脑损伤，为无法耐受药物治疗的患者提供了替代方案。针对再灌注损伤的机制干预取得突破，抑制血清和糖皮质激素调节激酶 1（SGK1）可减轻血脑屏障破坏，区域冷灌注联合血红蛋白基氧载体治疗能改善血流动力学、减少出血转化。（三）机械取栓与再生医学创新机械取栓器械不断升级，新型大口径吸引器（如JET 7 导管）结合球囊导管与支架取栓技术，首次通过再通成功率超 90%；复合取栓技术（如 BADDASS 技术）整合多重器械优势，进一步提升了复杂血管闭塞的再通质量。靶向溶栓剂研发聚焦于降低出血风险，局部低剂量溶栓联合机械取栓及纳米载体精准递送技术，减少了全身副作用。细胞治疗与再生医学成为修复领域核心方向。间充质干细胞（MSCs）与神经干细胞通过分泌营养因子、调节免疫炎症，显著促进神经功能恢复；MSC 来源的外泌体因低免疫原性和强穿脑能力，成为细胞移植的理想替代方案。生物材料与组织工程技术的结合，为干细胞定植提供了支架支持，中医药成分则可提升干细胞增殖分化能力，推动传统医学与再生医学的融合。三、病理机制解析：炎症与免疫调控的核心作用 2025 年研究进一步揭示了炎症与免疫反应在缺血性脑血管病中的双重作用，为靶向治疗提供了新靶点。炎症反应的阶段特异性功能得到明确：急性期内，缺血缺氧诱发 PGE2、IL-1β、TNF-α 等促炎介质释放，激活微胶质细胞与外周免疫细胞浸润，破坏血脑屏障并加剧神经损伤；慢性期则转向修复表型，IL-10 等抗炎因子分泌增加，免疫细胞参与神经修复与组织稳态重建。免疫细胞的功能分化机制成为研究重点，微胶质细胞在缺血后可从 M1 型促炎表型转化为 M2 型修复表型，浆细胞样树突状细胞通过诱导调节性 T 细胞（Tregs）扩增发挥免疫抑制作用，PD-1/PD-L1 轴与 NLRP3 炎症小体则调控免疫平衡与炎症激活。免疫调节治疗策略呈现 “双向调控” 特征：急性期采用小分子抑制剂与抗炎药物抑制过度炎症，慢性期则通过免疫激活剂促进修复表型转化；联合治疗（如抗氧化剂 + 免疫调节剂）协同调控氧化应激与炎症反应，纳米技术与细胞治疗的结合则实现了免疫调节的精准化。免疫相关生物标志物的监测的应用，为治疗效果评估提供了量化依据。四、总结与展望 2025 年缺血性脑血管病研究呈现 “精准化、个体化、多学科融合” 的核心趋势：诊断领域实现了影像、生物标志物与数字技术的多维整合，治疗领域突破了传统时间窗与人群限制，机制研究聚焦于炎症免疫的精准调控。然而，仍存在部分挑战，如新型药物与细胞治疗的长期安全性需大规模临床试验验证，个体差异对治疗效果的影响机制尚未完全明确，基础研究向临床转化的效率有待提升。未来研究应进一步强化基础与临床的结合，通过多中心协作积累真实世界数据，优化个体化治疗方案；推动神经科学、免疫学、纳米技术与数字健康的跨学科融合，开发更高效的诊断工具与治疗药物；关注不同地区、性别与年龄群体的疾病特征差异，制定差异化防控策略。通过这些举措，有望实现缺血性脑血管病从早期精准诊断到个性化治疗的全链条突破，降低疾病负担并提升患者生活质量参考文献 [1] Chen X, Lu L, Xiao C, et al. 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J Med Chem. 2020;63(13):6909-6923. doi:10.1021/acs.jmedchem.0c00285 https://pubmed.ncbi.nlm.nih.gov/32545964/ [48] Ito Y, Abumiya T, Komatsu T, et al. Neuroprotective effects of combination therapy of regional cold perfusion and hemoglobin-based oxygen carrier administration on rat transient cerebral ischemia. Brain Res. 1746:147012. doi:10.1016/j.brainres.2020.147012 https://pubmed.ncbi.nlm.nih.gov/32652148/ [49] Yang T, Jiang N, Han H, et al. Bibliometric Analysis of Stem Cells in Ischemic Stroke (2001-2022): Trends, Hotspots and Prospects. Int J Med Sci. 2024;21(1):151-168. Published 2024 None. doi:10.7150/ijms.86591 https://pubmed.ncbi.nlm.nih.gov/38164351/ [50] Guo Y, Peng Y, Zeng H, Chen G. Progress in Mesenchymal Stem Cell Therapy for Ischemic Stroke. Stem Cells Int. 2021:9923566. Published 2021 None. doi:10.1155/2021/9923566 https://pubmed.ncbi.nlm.nih.gov/34221026/ [51] Oliva AA, McClain-Moss L, Pena A, Drouillard A, Hare JM. 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2025-10-23

·三优生物医药

三优十周年｜神经系统疾病治疗进展

作者：金汉卿美工：何国红罗真真排版：马超 01 引言延长预期寿命可谓人类公共卫生领域最伟大的成就之一。然而，寿命的增长也伴随与年龄相关的神经系统疾病 (Neurological disorders) 负担不断攀升。神经系统疾病是指发生于中枢或周围神经系统、以感觉、意识、运动等功能受损为主要表现的一类疾病，整体呈现低病死率、高致残率的特点。就在2025年10月14日，世界卫生组织发布了新的《全球神经病学状况报告》1，报告显示神经系统疾病目前影响着全球40%以上的人口——超过30亿人，造成4.35亿伤残调整生命年 (DALY) ，使其成为全球疾病与残疾的主要原因。37种神经系统疾病共导致1180万人死亡、1.62亿年残疾生活年与2.72亿年寿命损失。本文聚焦若干神经系统疾病的治疗前沿，旨在为行业专业人士提供可操作的靶点开发参考。 ▲ 图1：影响神经系统疾病的全球负担2 02 阿尔兹海默病阿尔茨海默病 (Alzheimer’s disease, AD) 是一种以进行性认知障碍为核心表现的中枢神经系统退行性疾病。其病理特征包括淀粉样β (Aβ) 斑块沉积与Tau蛋白异常磷酸化/神经原纤维缠结，并常伴随神经炎症与突触功能障碍。近年，基于脑脊液/影像的病理分层逐步延伸至血液标志物 (如血浆p tau217) ，为早期识别与入组提供更可及的工具。 ▲ 图2：阿尔茨海默病的病理机制3 目前的治疗以对症药物 (胆碱酯酶抑制剂与NMDA受体拮抗剂) 和在早期人群中使用的疾病修饰疗法为主。抗Aβ单抗方面，lecanemab (Leqembi) 已在2023年获FDA批准，而donanemab (Kisunla) 也于2024年获FDA批准用于早期症状性AD (MCI/轻度痴呆) 并按月静脉给药。临床实践通常需要影像/体液证据确认Aβ阳性，并在治疗过程中进行MRI监测以管理ARIA。 • 药物前沿进展聚焦三条主线：抗Aβ策略升级：已上市抗体在早期人群显示减缓进展的临床获益。为实现更高的皮层暴露，罗氏开发Brainshuttle技术，通过偶联可结合转铁蛋白受体 (TfR) 的模块，显著提高穿透BBB能力与脑内分布。抗Tau与联合方案：多款抗Tau通路药物推进中。尽管单药结果不积极，但与Aβ清除形成序贯/联合方案，有望影响下游神经退行改变。炎症抑制与精准分层：围绕神经炎症的多靶点布局逐步成形。例如选择性中和可溶性TNF的XPro™/XPro1595：II期MINDFuL总体未达主要终点，但在炎症生物标志物富集的早期AD亚组出现认知、行为与生物学端点的获益信号，且安全性良好，提示“炎症表型分层”的精准用药方向。 ▲ 图3：阿尔茨海默病的在研药物靶点汇总 03 帕金森病帕金森病 (Parkinson’s disease, PD) 是一种影响中枢神经系统、以运动系统受累为主的慢性神经退行性疾病，症状通常缓慢进展。静止性震颤、肌强直、运动迟缓与步态异常常见于早期，也可伴随认知与行为改变。病理学上，以黑质多巴胺能神经元丢失及细胞内α‑突触核蛋白聚集为特征；早期退变多局限于腹外侧黑质，随病程推进而扩展。路易体主要由聚集的α‑突触核蛋白组成，病变通常自脑干胆碱能/单胺能神经元与嗅觉系统起始，随后累及边缘系统和新皮质。 ▲ 图4：帕金森病的病理机制4 现行治疗方面，左旋多巴及多巴胺替代治疗仍为金标准。早期可用左旋多巴单药，或联合多巴胺激动剂 (如罗匹尼罗、普拉克索、罗替戈汀) 及MAO‑B抑制剂 (如司来吉兰、雷沙吉兰) 。与早期左旋多巴单药相比，早期启用多巴胺激动剂对长期残疾与生活质量并无显著优势。对出现“开-关”波动者，常通过缩短左旋多巴给药间隔，联合COMT抑制剂 (恩他卡朋、阿匹卡朋) 和/或MAO-B抑制剂 (司来吉兰、雷沙吉兰、沙芬酰胺、唑尼沙胺) ，并调增多巴胺激动剂；若出现异动症，可加用金刚烷胺；部分合适人群可考虑设备辅助治疗以缩短“关”期并改善运动障碍。 • 药物/技术前沿主要包括：靶向α‑突触核蛋白的被动免疫：临床前可改善病理与行为。两项大型早期PD试验 (SPARK/cinpanemab与PASADENA/prasinezumab) 虽未达主要终点，PASADENA显示运动进展减缓趋势。基于2b期PADOVA及其OLE与PASADENA长随，罗氏已推进prasinezumab进入III期。 LRRK2降解/抑制策略：LRRK2为公认关键靶点。2025年10月8日，Arvinas公布ARV‑102 (LRRK2降解剂) I期积极数据，显示良好的脑脊液暴露与显著的靶蛋白下调 (外周>90%，脑脊液>50%) ，并伴随pRab10与尿BMP等下游生物标志物降低。基因治疗：AAV2‑GAD向丘脑底核递送在晚期PD中证实安全并带来治疗侧改善；AAV2‑AADC在壳核过表达可增强左旋多巴转化，6个月UPDRS (用药/停药) 约三成改善且用药剂量下降，但4年随访提示临床收益逐步回归基线，提示需进一步优化递送与联合策略。 ▲ 图5：帕金森病的在研药物靶点汇总 04 中风中风 (Stroke，脑卒中) 包括缺血性与出血性两大类，其中以缺血性为主。其发病机制中，缺血造成的级联反应涉及多种中枢神经系统细胞：在缺血核心，神经元发生形态改变，细胞体与轴突消失；小胶质细胞、星形胶质细胞亦随之发生反应性改变。缺血后BBB通透性增加，多种免疫细胞 (白细胞、单核细胞、巨噬细胞) 浸润病灶区，释放神经毒性或神经营养因子，对受损脑组织产生既可能保护亦可能有害的影响。 ▲ 图6：脑卒中的病理机制5 现行治疗策略强调“急性再灌注+二级预防”两端发力。针对急性期，发病4.5小时内静脉溶栓仍为基础。除阿替普酶外，多项指南与综述支持替奈普酶 (TNK) 0.25 mg/kg在部分场景作为替代选择；对大血管闭塞患者，借助灌注成像选择性入组，机械取栓时间窗可拓至6–24小时。针对二级预防，小卒中/高危TIA人群的短期双联抗血小板 (阿司匹林+氯吡格雷) 获益主要集中在起始后21天内；合并房颤者以口服抗凝 (优选DOACs) 为一线，无法长期抗凝者可考虑左心耳封堵 (LAAO) 作为替代或补充方案。 • 药物/技术前沿主要体现在：靶向药： 1. glenzocimab (抗GPVI) 旨在在降低血栓形成的同时控制出血风险； 2. 3K3A‑APC兼具神经与血管保护，早期研究显示良好安全性与出血相关指标改善信号； 3. nerinetide (PSD‑95抑制肽) 总体结论中性，但在未合用tPA或特定流程亚群显现潜在获益，提示存在人群与流程依赖性。细胞与基因治疗： 1. SB623 (基因改造间充质基质细胞) 用于慢性期功能重建显示上肢运动量表改善且安全性良好； 2. MultiStem (同种异体MAPC) 在18–36小时给药窗内安全可行，关键III期验证持续； 3. AAV递送 (如VEGF/神经营养因子/抗炎因子) 临床前证据积极，但跨BBB的安全与递送效率仍是转化瓶颈。 ▲ 图7：脑卒中的在研药物靶点汇总 05 其他神经系统疾病及治疗前沿除AD、PD与中风外，神经系统疾病还包括多发性硬化 (MS)、视神经脊髓炎谱系疾病 (NMOSD) 、肌萎缩侧索硬化 (ALS)、重症肌无力 (gMG) 、偏头痛等。随着靶向药与技术平台的演进，越来越多的创新疗法为不同疾病带来新的治疗希望： NMOSD：已有三条机制获批——补体C5抑制剂 (依库珠单抗/拉夫珠单抗) 、抗CD19 (伊妥珠单抗/inebilizumab) 、抗IL‑6R (沙妥利珠单抗/satralizumab) 。偏头痛：中枢敏化与CGRP通路为关键机制。美国头痛学会已将CGRP疗法 (艾伦单抗/芙马珠单抗/加拉单抗/艾普替单抗) 纳入一线预防选项。 gMG：FcRn拮抗剂 (efgartigimod、rozanolixizumab) 与补体C5抑制剂 (eculizumab、ravulizumab) 确立了分子靶向治疗范式，显著改善症状、加速缓解。 • 基因疗法亦加速进入临床：亨廷顿病 (HD)：等位基因选择性ASO (WVE‑003) 实现突变HTT下调且安全性可接受；AMT‑130 (AAV‑miHTT) I/II期长随提示疾病进展减缓信号。难治性癫痫：ASO上调SCN1A (zorevunersen/STK‑001) 在早期研究显示发作频率下降与行为/认知改善信号；基因调控疗法ETX101 (AAV9) 在SCN1A+德拉维特综合征进入I/II期；抑制性中间神经元细胞疗法NRTX‑1001在成人MTLE一期呈现发作显著降低与良好耐受性。脊髓性肌萎缩 (SMA)：已建立三大治疗支柱——ASO (nusinersen) 、基因疗法 (AAV9‑SMN1，onasemnogene abeparvovec) 与口服小分子剪接调节剂 (risdiplam) 。 06 神经系统疾病治疗总结神经系统疾病呈“低病死、高致残”特征，已成全球疾病负担首因。治疗正由对症控制走向“疾病修饰+精准分层”。阿尔茨海默病方面，抗Aβ单抗 (lecanemab、donanemab) 在早期人群证实减缓进展，血液标志物与穿越BBB的递送技术 (如Brainshuttle) 加速落地，抗Tau与抗炎 (如选择性中和可溶性TNF) 成为重要补充。帕金森病仍以多巴胺替代为基石，但围绕α-突触核蛋白的免疫、LRRK2抑制/降解与基因治疗正在逼近关键验证。中风治疗两端发力：急性期强调再灌注 (TNK与晚窗机械取栓) ，二级预防重视分型与个体化 (短期DAPT、DOACs、LAAO) 。除AD/PD/中风外，NMOSD、gMG、偏头痛已形成明确分子靶向范式；HD、癫痫、SMA等病种的基因/细胞疗法进展迅速。 • 针对神经系统疾病的未来治疗方向将聚焦于： ① 跨BBB递送与长效化——TfR介导、脑内暴露定量学、皮下长效制剂； ② 基因治疗——AAV/ASO精准调控与免疫规避，提升持续表达与安全窗； ③ AOC药物——抗体-寡核苷酸偶联，实现细胞/区域特异输送与基因沉默、上调或剪接校正，为难治性癫痫、遗传性运动障碍等提供新解。 Sanyou 10th Anniversary: Therapeutic Advances in Neurological Disorders 01 Introduction Extending life expectancy is one of humanity’s greatest public-health achievements. Yet longer lives come with a steadily rising burden of age-related neurological disorders. Neurological disorders—conditions of the central or peripheral nervous system characterized primarily by impairments of sensation, consciousness, and movement—generally have low case-fatality but high disability rates. On October 14, 2025, the World Health Organization released a new Global Status Report on Neurology1, estimating that neurological disorders currently affect over 40% of the world’s population—more than 3 billion people—and account for 435 million disability-adjusted life years (DALYs), making them the leading cause of disease and disability worldwide. Across 37 neurological conditions, there were 11.8 million deaths, 162 million years lived with disability, and 272 million years of life lost. This article highlights therapeutic frontiers across selected neurological diseases to provide actionable target ideas for R&D professionals. ▲ Fig. 1 Global burden of conditions affecting the nervous system2 02 Alzheimer’s Disease Alzheimer’s disease (AD) is a progressive, degenerative disorder of the central nervous system whose core clinical feature is cognitive decline. Pathology includes extracellular amyloid-β (Aβ) plaque deposition and abnormal phosphorylation of tau protein/neurofibrillary tangles, often accompanied by neuroinflammation and synaptic dysfunction. In recent years, pathology-based stratification via CSF/imaging has extended to blood biomarkers (e.g., plasma p-tau217), providing more accessible tools for early identification and trial enrollment. ▲ Fig. 2 Pathology of Alzheimer’s disease3 • Current therapies Management combines symptomatic agents (cholinesterase inhibitors and the NMDA receptor antagonist memantine) with disease-modifying therapy initiated in early-symptomatic populations. Among anti-Aβ monoclonal antibodies, lecanemab (Leqembi) received traditional FDA approval in 2023 with labeling that emphasizes ARIA risk and APOE ε4 stratification; donanemab (Kisunla) was approved in 2024 for early symptomatic AD (MCI/mild dementia) and is administered as monthly IV infusions. In clinical practice, Aβ positivity is typically confirmed by imaging or fluid biomarkers, and MRI monitoring is used during treatment to manage ARIA. • Frontline R&D themes Upgrading anti-Aβ strategies. Marketed antibodies show clinically meaningful slowing in early-stage populations. To achieve higher cortical exposure, Roche is developing Brainshuttle technology by coupling to transferrin receptor (TfR)–binding modules, markedly improving BBB penetration and brain distribution. Anti-tau and combination/sequencing. Multiple programs targeting tau pathways are advancing. Although monotherapy results have been mixed, pairing with Aβ clearance in sequential/combination regimens may modulate downstream neurodegeneration. Inflammation control with precise stratification. A growing multi-target portfolio focuses on neuroinflammation. For example, selective neutralization of soluble TNF with XPro™/XPro1595 missed the primary endpoint in the phase II MINDFuL study overall, but showed signals of benefit across cognitive, behavioral, and biomarker endpoints in an inflammation-enriched early-AD subgroup with good safety—supporting “inflammatory phenotype stratification” for precision use. ▲ Fig. 3 Drug targets under development for Alzheimer’s disease 03 Parkinson’s Disease Parkinson’s disease (PD) is a chronic neurodegenerative disorder primarily affecting the motor system with typically slow progression. Early features include resting tremor, rigidity, bradykinesia, and gait disturbance, often with cognitive/behavioral changes. Pathology features loss of dopaminergic neurons in the substantia nigra and intracellular α-synuclein aggregation; early degeneration is often localized to the ventrolateral substantia nigra and expands with disease. Lewy bodies are mainly composed of aggregated α-synuclein, with lesions commonly starting in brainstem cholinergic/monoaminergic neurons and the olfactory system, then involving limbic structures and neocortex. ▲ Fig. 4 Pathology of Parkinson’s disease4 • Current therapies There is no established disease-modifying therapy. Levodopa and dopamine replacement remain the gold standard. Early treatment can be levodopa monotherapy or combined with dopamine agonists (e.g., ropinirole, pramipexole, rotigotine) and MAO-B inhibitors (e.g., selegiline, rasagiline). Compared with early levodopa monotherapy, starting dopamine agonists early shows no clear advantage for long-term disability or quality of life. For “on–off” fluctuations, clinicians often shorten levodopa dosing intervals, add COMT inhibitors (entacapone, opicapone) and/or MAO-B inhibitors (selegiline, rasagiline, safinamide, zonisamide), and titrate dopamine agonists; amantadine may be added for dyskinesia. Device-aided therapies can be considered in selected patients to reduce “off” time and improve motor complications. • Frontline R&D themes Passive immunotherapy against α-synuclein. Preclinical data show improvements in pathology and behavior. Although two large early-PD trials (SPARK/cinpanemab and PASADENA/prasinezumab) missed primary endpoints, PASADENA showed a trend toward slower motor progression. Based on phase 2b PADOVA and its OLE plus long-term PASADENA follow-up, Roche has advanced prasinezumab into phase III. LRRK2 inhibition/degradation. LRRK2 is a validated target. On October 8, 2025, Arvinas reported positive phase I data for the LRRK2 degrader ARV102, showing good CSF exposure and robust target knock-down (>90% peripherally, >50% in CSF) with reductions in downstream biomarkers (pRab10 and urinary BMP). Gene therapy. AAV2-GAD delivery to the subthalamic nucleus showed safety and improvement on the treated side in advanced PD; AAV2-AADC overexpression in the putamen enhances levodopa conversion, producing ~30% improvement in UPDRS (on/off medication) at 6 months and reduced medication needs, though 4-year follow-up suggests benefits trend back toward baseline—highlighting the need to optimize delivery and combinations. ▲ Fig. 5 Drug targets under development for Parkinson’s disease 04 Stroke Stroke comprises ischemic and hemorrhagic types, with ischemic stroke predominating. The ischemic cascade involves multiple CNS cell types: in the core, neurons undergo morphological changes with loss of soma and axons; microglia and astrocytes also react. Post-ischemia, BBB permeability increases; leukocytes, monocytes, and macrophages infiltrate the lesion, releasing either neurotoxic or neurotrophic factors with potentially protective or harmful effects on injured brain tissue. ▲ Fig. 6 Pathology of stroke5 • Current strategies Management emphasizes both acute reperfusion and secondary prevention. For the acute phase, IV thrombolysis within 4.5 hours remains foundational. Beyond alteplase, guidelines and reviews support tenecteplase (TNK) 0.25 mg/kg as an alternative in selected scenarios. For large-vessel occlusion, perfusion-imaging–guided selection enables mechanical thrombectomy in the 6–24 hour window. For secondary prevention, short-term dual antiplatelet therapy (aspirin + clopidogrel) in minor stroke/high-risk TIA confers most of its benefit within 21 days of initiation. In patients with atrial fibrillation, oral anticoagulation (preferably DOACs) is first-line; when long-term anticoagulation is unsuitable, left atrial appendage occlusion (LAAO) can be considered as an alternative or adjunct. • Frontline R&D themes Targeted agents： 1. glenzocimab (anti-GPVI): aims to curb thrombosis while controlling bleeding risk. 2. 3K3A-APC: offers neuro- and vasculo-protection; early studies suggest good safety and favorable bleeding-related signals. 3. nerinetide (PSD-95 inhibitor peptide): neutral overall, but potential benefit in subgroups not receiving tPA or under specific workflow conditions—suggesting population/process dependence. Cell and gene therapies：1. SB623 (gene-modified mesenchymal stromal cells) for chronic-phase functional recovery improved upper-limb scales with good safety. 2. MultiStem (allogeneic MAPC) appears safe/feasible with dosing at 18–36 hours; pivotal phase III confirmation is ongoing. 3. AAV delivery (e.g., VEGF/neurotrophic/anti-inflammatory factors) shows encouraging preclinical evidence, but safe and efficient BBB crossing remains a translational bottleneck. ▲ Fig. 7 Drug targets under development for stroke 05 Other Neurological Diseases and Therapeutic Frontiers Beyond AD, PD, and stroke, neurological disorders include multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), amyotrophic lateral sclerosis (ALS), generalized myasthenia gravis (gMG), migraine, and more. With the evolution of targeted drugs and platform technologies, an expanding array of innovative therapies is delivering new hope:NMOSD: Three approved mechanisms—complement C5 inhibitors (eculizumab/ravulizumab), anti-CD19 (inebilizumab), and anti-IL-6R (satralizumab). Migraine: Central sensitization and the CGRP pathway are key. The American Headache Society now lists CGRP-pathway therapies (erenumab, fremanezumab, galcanezumab, eptinezumab) as first-line options for prevention. gMG: FcRn antagonists (efgartigimod, rozanolixizumab) and complement C5 inhibitors (eculizumab, ravulizumab) have established a molecularly targeted paradigm, improving symptoms and accelerating remission. • Gene and cell therapies accelerating into the clinicHuntington’s disease (HD): Allele-selective ASO WVE-003 lowers mutant HTT with acceptable safety; AMT-130 (AAV-miHTT) phase I/II long-term follow-up suggests signals of slowed disease progression. Refractory epilepsy: ASO zorevunersen/STK-001 upregulates SCN1A with early signals of seizure reduction and behavioral/cognitive improvement; gene-regulation therapy ETX101 (AAV9) has entered phase I/II for SCN1A-positive Dravet syndrome; an inhibitory interneuron cell therapy NRTX1001 in adult MTLE phase I shows marked seizure reduction with good tolerability. Spinal muscular atrophy (SMA): A tri-pillar framework is established—ASO (nusinersen), gene therapy (onasemnogene abeparvovec, AAV9-SMN1), and oral small-molecule splicing modulation (risdiplam). 06 Summary of Therapeutic Directions Neurological disorders feature low mortality but high disability , now the top contributor to global disease burden. Treatment is shifting from symptomatic control to disease modification with precise stratification.AD: Anti-Aβ antibodies (lecanemab, donanemab) slow progression in early populations; blood biomarkers and BBB-shuttling technologies (e.g., Brainshuttle) are moving into practice. Anti-tau and anti-inflammatory approaches (e.g., selective neutralization of soluble TNF) are important complements. PD: Dopamine replacement remains foundational, while α-synuclein immunotherapy, LRRK2 inhibition/degradation, and gene therapy approach key validation milestones. Stroke: Dual-pronged care—acute reperfusion (TNK and extended-window thrombectomy) and individualized secondary prevention (short-term DAPT, DOACs, LAAO). Others: NMOSD, gMG, and migraine already have clear targeted paradigms; gene/cell therapies are rapidly advancing in HD, epilepsy, SMA, and beyond. • Future priorities will focus on1. Cross-BBB delivery and durability—TfR-mediated shuttles, quantitative CNS exposure, and long-acting subcutaneous formulations. 2. Gene therapy—AAV/ASO precision control with immune evasion, enhancing persistence and safety margins. 3. AOC (antibody–oligonucleotide conjugates)—cell/region-specific delivery enabling gene silencing, up-regulation, or splice correction, offering new solutions for refractory epilepsy, inherited movement disorders, and more. ▶ Ref 1. Global status report on neurology 2. GBD 2021 Nervous System Disorders Collaborators. Global, regional, and national burden of disorders affecting the nervous system, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Neurol. 2024;23(4):344-381. doi:10.1016/S1474-4422(24)00038-3 3. Kamatham PT, Shukla R, Khatri DK, Vora LK. Pathogenesis, diagnostics, and therapeutics for Alzheimer's disease: Breaking the memory barrier. Ageing Res Rev. 2024;101:102481. doi:10.1016/j.arr.2024.102481 4. Morris HR, Spillantini MG, Sue CM, Williams-Gray CH. The pathogenesis of Parkinson's disease. Lancet. 2024;403(10423):293-304. doi:10.1016/S0140-6736(23)01478-2 5. Qin C, Yang S, Chu YH, et al. Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions. Signal Transduct Target Ther. 2022;7(1):215. Published 2022 Jul 6. doi:10.1038/s41392-022-01064-1 1 推荐阅读三优十周年｜AI-STAL 智能超万亿分子库发展历程三优十周年｜打造全球顶尖的原创新药创新工场三优十周年｜抗体治疗50年风雨江湖三优十周年｜针对宠物疾病的单克隆抗体药物三优十周年｜CAR-T细胞治疗现状挑战与未来三优十周年｜服务篇-体外药效筛选解决方案三优十周年｜AI-STAL篇-Anticalin靶向蛋白库三优十周年｜靶点篇-自身免疫疾病靶点介绍创新前沿｜三优生物类器官产学研联盟启航中和抗体“硬核出击”，斩断CHIKV病毒感染链三优十周年｜服务篇-靶点至PCC药物研发三优十周年｜靶点篇-六大恶性肿瘤靶点介绍创新前沿｜2025ADC热门靶点与技术创新启示三优十周年｜AI-STAL篇-高等电点单域抗体库 6类分子形式之环状多肽分子产生系统解决方案关于三优生物三优生物是一家以“让天下没有难做的创新生物药”为使命，以超万亿分子库和智能科技驱动的生物医药高科技企业。公司致力于打造全球顶尖的原创新药创新工场。公司以智能超万亿分子库（AI-STAL）为核心；以干湿结合、国际领先的创新生物药智能化及一体化研发平台为依托；以多样化的业务模式推动全球创新药物的研发及产业化。公司总部位于中国上海，在亚洲、北美洲、欧洲等多地建立了业务中心，形成了全球化的业务网络，现有投产及布局的研发及GMP场地20000多平方米。公司已与全球2000多家药企、生技公司等建立了良好的合作关系，已赋能1200多个新药研发项目；已完成50多个合作研发项目，其中10多个协同研发项目已推至IND及临床研发阶段。公司已申请130多项发明专利，其中30多项发明专利已获得授权，并获得了国家级高新技术企业、上海市专精特新、ISO9001、ISO27001等10余项资质及体系认证。 11

临床研究临床结果

100 项与 Nerinetide 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11729	-	-	DB12595

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
急性缺血性卒中	临床3期	美国	NoNO, Inc.	2017-03-01
急性缺血性卒中	临床3期	澳大利亚	NoNO, Inc.	2017-03-01
急性缺血性卒中	临床3期	加拿大	NoNO, Inc.	2017-03-01
急性缺血性卒中	临床3期	德国	NoNO, Inc.	2017-03-01
急性缺血性卒中	临床3期	爱尔兰	NoNO, Inc.	2017-03-01
急性缺血性卒中	临床3期	瑞典	NoNO, Inc.	2017-03-01
急性缺血性卒中	临床3期	英国	NoNO, Inc.	2017-03-01
脑缺血	临床3期	加拿大	NoNO, Inc.	2015-03-26
颅内动脉瘤	临床2期	美国	NoNO, Inc.	2015-11-01
颅内动脉瘤	临床2期	加拿大	NoNO, Inc.	2015-11-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04462536 (ESCAPE-NEXT, CTgov)	临床3期	急性缺血性卒中	850	Placebo (Placebo)	淵簾夢願繭夢膚醖夢網 = 築鏇範觸願鹽顧壓糧鑰網襯醖願願獵繭鏇製簾 (餘鏇積顧鏇構糧鏇鬱糧, 簾襯衊壓鹽繭顧夢壓齋 ~ 製廠憲憲網窪網憲蓋鏇) 更多	-	2025-06-22
				Nerinetide (Nerinetide)	淵簾夢願繭夢膚醖夢網 = 鹽鬱顧範鏇艱鏇壓願遞網襯醖願願獵繭鏇製簾 (餘鏇積顧鏇構糧鏇鬱糧, 鹽簾築鏇齋鹹遞鏇窪壓 ~ 簾蓋製鏇醖願製鏇鑰築) 更多
NCT02930018 (ESCAPE-NA1, Pubmed \| Neurology)	临床3期	脑卒中	-	Nerinetide	醖齋膚鏇鬱選範窪簾範(淵網憲憲繭網夢淵鏇鹹) = 糧艱繭繭繭壓願襯廠積醖願獵鹹艱觸襯繭膚廠 (夢鏇餘鑰鹽製蓋積顧窪, 1.09 ~ 21.30) 更多	不佳	2024-01-23
				Placebo	醖齋膚鏇鬱選範窪簾範(淵網憲憲繭網夢淵鏇鹹) = 繭窪範窪艱積範遞構製醖願獵鹹艱觸襯繭膚廠 (夢鏇餘鑰鹽製蓋積顧窪, 2.54 ~ 21.81) 更多
NCT00728182 (ENACT, AAN2022)	临床2期	脑梗塞	184	Nerinetide treatment	窪觸獵艱願糧艱遞獵窪(窪艱醖鑰鬱獵膚襯遞鹹): P-Value = 0.020 更多	积极	2022-05-03
				Placebo
NCT02930018 (REPERFUSE-NA1, ISC2022)	临床3期	梗塞	71	NA1	鏇襯鹹鏇鏇艱膚壓積蓋(築鏇鹽衊糧壓襯艱遞艱) = 築鹹積構製廠鹽鏇餘繭遞繭膚醖窪鑰觸鬱醖顧 (糧觸積獵築製夢淵鹽醖, 5.9 ~ 28.1) 更多	-	2022-02-01
				Placebo	鏇襯鹹鏇鏇艱膚壓積蓋(築鏇鹽衊糧壓襯艱遞艱) = 衊繭壓簾遞鑰鹽衊膚積遞繭膚醖窪鑰觸鬱醖顧 (糧觸積獵築製夢淵鹽醖, 3.1 ~ 27.0) 更多
NCT02930018 (ESCAPE-NA1 \| REPERFUSE-NA1, CTgov)	临床3期	急性缺血性卒中	1,105	Placebo	鹽選憲遞鬱範觸鑰淵簾 = 遞膚獵憲淵壓糧遞積壓遞顧選遞憲壓構淵構獵 (蓋繭製襯構齋鹹憲簾鏇, 憲鏇簾願衊醖憲願醖鬱 ~ 餘觸網憲築餘鑰獵淵廠) 更多	-	2020-12-14
NCT02930018 (ESCAPE-NA1, Pubmed \| Lancet) 人工标引	临床3期	急性缺血性卒中	1,105	nerinetide	憲觸鬱構齋膚繭築鹹艱(憲網憲積範觸衊積壓鹽) = Serious adverse events occurred equally between groups. 淵築選鬱襯窪顧顧獵鏇 (範憲選繭網糧壓顧糧願 ) 更多	不佳	2020-03-14
				Placebo
NCT00728182 (ENACT, CTgov)	临床2期	脑卒中 \| 动脉瘤 \| 缺血性卒中 ... 更多	185	NA-1 (1 NA-1)	願襯顧窪鏇餘夢醖窪繭(襯鹽遞膚選窪艱選廠膚) = 繭餘繭夢鑰獵壓襯蓋廠獵網鹽鏇淵願積構範齋 (積願膚醖製醖壓鬱觸觸, 5598) 更多	-	2013-10-17
				placebo (2 Placebo)	願襯顧窪鏇餘夢醖窪繭(襯鹽遞膚選窪艱選廠膚) = 廠築膚製襯網網艱餘鬱獵網鹽鏇淵願積構範齋 (積願膚醖製醖壓鬱觸觸, 1611) 更多