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]

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.

NCT02315443 / Completed临床3期

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of Intravenous NA-1 Initiated by Paramedics in the Field for Acute Cerebral Ischemia Within Three Hours of Symptom Onset

The purpose of this study is to determine whether nerinetide (NA-1) is effective in reducing global disability in patients with acute cerebral ischemia if administered early after symptom onset.

开始日期2015-03-26

申办/合作机构

NoNO, Inc.

[+7]

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）

2024-12-01·JOURNAL OF THE NEUROLOGICAL SCIENCES

Prevalence of ipsilateral “vulnerable carotid plaques with <50 % stenosis” on CT angiography in embolic stroke of undetermined source

Article

作者: Poppe, Alexandre Y. ; Poppe, Alexandre Y ; Stebner, Alexander ; Almekhlafi, Mohammed A ; Buck, Brian ; Almekhlafi, Mohammed A. ; Singh, Nishita ; Hill, Michael D. ; Ospel, Johanna M. ; Goyal, Mayank ; Uchida, Kazutaka ; Marko, Martha ; Hill, Michael D ; Bosshart, Salome ; Demchuk, Andrew M ; Demchuk, Andrew M. ; Ganesh, Aravind ; Ospel, Johanna M

BACKGROUND:

Carotid plaques may be an important etiology in ischemic stroke. We aimed to assess carotid plaque characteristics ipsilateral and contralateral to the ischemic stroke and assessed the prevalence of "vulnerable carotid plaques with <50% stenosis" based on different imaging-based definitions in patients with large vessel occlusion and source of embolic stroke of undetermined source (ESUS) on CT Angiography (CTA).

METHODS:

Data are from the ESCAPE-NA1 trial (Efficacy and safety of nerinetide for the treatment of acute ischemic stroke), a multicenter, randomized study that included anterior circulation large vessel occlusion patients undergoing thrombectomy. Various CTA features of plaque vulnerability were combined to define "vulnerable carotid plaques" in different ways. Within ESUS patients, prevalence of vulnerable plaques ipsilateral vs. contralateral to the intracranial occlusion was compared.

RESULTS:

We analyzed 132 patients whose ischemic stroke mechanism was determined to be ESUS. Plaques causing 30-50 % stenosis (as compared to no stenosis) and plaque surface irregularity were significantly more common in ipsilateral carotid arteries (37[28.0 %] vs. 18[13.6 %]; p < 0.001 and 102[77.3 %] vs. 78[59.1 %]; p = 0.002). The prevalence of ipsilateral "vulnerable carotid plaques" varied depending on imaging definition used for such plaques between 55 and 74 %, but irrespective of the definition used, the prevalence of "vulnerable carotid plaques" was consistently higher in ipsilateral carotid arteries compared to contralateral carotid arteries.

CONCLUSIONS:

In ESUS patients undergoing thrombectomy for anterior circulation large vessel occlusion, vulnerable carotid plaques are more prevalent ipsilateral to the intracranial occlusion. Irregular plaque surface, and a higher degree of stenosis were the most common vulnerable plaque features.

2024-08-01·STROKE

HERMES-24 Score Derivation and Validation for Simple and Robust Outcome Prediction After Large Vessel Occlusion Treatment.

Article

作者: White, Phil M ; Campbell, Bruce C V ; Brown, Scott ; Muir, Keith W ; Jovin, Tudor G ; van Zwam, Wim H ; Tanaka, Koji ; Najm, Mohamed ; Bracard, Serge ; Demchuk, Andrew M ; Guillemin, Francis ; Roos, Yvo B W E M ; Mitchell, Peter J ; Menon, Bijoy K ; Dowlatshahi, Dar ; Goyal, Mayank ; Saver, Jeffrey L ; Hill, Michael D

BACKGROUND:

Clinicians need simple and highly predictive prognostic scores to assist practical decision-making. We aimed to develop a simple outcome prediction score applied 24 hours after anterior circulation acute ischemic stroke treatment with endovascular thrombectomy and validate it in patients treated both with and without endovascular thrombectomy.

METHODS:

Using the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration data set (n=1764), patients in the endovascular thrombectomy arm were divided randomly into a derivation cohort (n=430) and a validation cohort (n=441). From a set of candidate predictors, logistic regression modeling using forward variable selection was used to select a model that was both parsimonious and highly predictive for modified Rankin Scale (mRS) ≤2 at 90 days. The score was validated in validation cohort, control arm (n=893), and external validation cohorts from the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke; n=1066) and INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography; n=614).

RESULTS:

In the derivation cohort, we selected 2 significant predictors of mRS ≤2 (National Institutes of Health Stroke Scale score at 24 hours and age [β-coefficient, 0.34 and 0.06]) and derived the HERMES-24 score: age (years)/10+National Institutes of Health Stroke Scale score at 24 hours. The HERMES-24 score was highly predictive for mRS ≤2 (c-statistic 0.907 [95% CI, 0.879-0.935]) in the derivation cohort. In the validation cohort and the control arm, the HERMES-24 score predicts mRS ≤2 (c-statistic, 0.914 [95% CI, 0.886-0.944] and 0.909 [95% CI, 0.887-0.930]). Observed provability of mRS ≤2 ranged between 3.1% and 3.4% when HERMES-24 score ≥25, while it ranged between 90.6% and 93.0% when HERMES-24 score <10 in the derivation cohort, validation cohort, and control arm. The HERMES-24 score also showed c-statistics of 0.894 and 0.889 for mRS ≤2 in the ESCAPE-NA1 and INTERRSeCT populations.

CONCLUSIONS:

The post-treatment HERMES-24 score is a simple validated score that predicts a 3-month outcome after anterior circulation large vessel occlusion stroke regardless of intervention, which helps prognostic discussion with families on day 2.

2024-07-01·JAMA Neurology

Time From Hospital Arrival Until Endovascular Thrombectomy and Patient-Reported Outcomes in Acute Ischemic Stroke

Article

作者: Brian A, van Adel ; Field, Thalia S. ; Hana, Choe ; Ajit S, Puri ; Rempel, Jeremy L. ; Marie-Christine, Camden ; Donald, Heck ; Frank L, Silver ; Daniel, Roy ; Ji Heo, Heo ; Tymianski, Michael ; Kennth S, Butcher ; Joung-Ho, Rha ; Ruchir A, Shah ; Michael D, Hill ; Goyal, Mayank ; Puetz, Volker ; Jeanne, Teitelbaum ; Richard H, Swartz ; Hill, Michael D. ; Campbell, Bruce ; Aditya, Bharatha ; Eric, Sauvageau ; Ryan A, McTaggart ; Smith, Eric E. ; Mayank, Goyal ; Demchuk, Andrew M. ; Joseph L, Schindler ; Oh Young, Bang ; Volker, Puetz ; Marios-Nikos, Psychogios ; Sauvageau, Eric ; Bruce CV, Campbell ; Ronald F, Budzik ; Michael, Mayich ; Sahlas, Jim ; Poppe, Alexandre Y. ; McTaggart, Ryan A. ; Demetrios J, Sahlas ; Ashutosh, Jadhav ; Paul A, Burns ; Rishi, Gupta ; Swartz, Richard ; David T, Parrella ; Coleman O, Martin ; Raul, Nogueira ; Brian H, Buck ; Joundi, Raed A. ; John, Thornton ; Ganesh, Aravind ; Jennifer L, Mandzia ; Jason W, Tarpley ; Sean, Murphy ; Donald F, Frei ; Andrew M, Demchuk ; Alexandre Y, Poppe ; Stephn J, Phillips ; Sidney, Starkman ; Bijoy K, Menon ; Shah, Ruchir ; Simon, Nagel ; Götz, Thomalla ; Cameron G, McDougall ; Chapot, René ; Dar, Dowlatshahi ; Nogueira, Raul G. ; Timothy J, Kleinig ; Silver, Frank L. ; Thalia S, Field ; Sung-Il, Sohn ; George A, Lopez ; Joey D, English ; René, Chapot ; Staffan, Holmin ; Dowlatshahi, Dar ; Chang-Hyun, Kim ; Michael E, Kelly

Importance:

The time-benefit association of endovascular thrombectomy (EVT) in ischemic stroke with patient-reported outcomes is unknown.

Objective:

To assess the time-dependent association of EVT with self-reported quality of life in patients with acute ischemic stroke.

Design, Setting, and Participants:

Data were used from the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, which tested the effect of nerinetide on functional outcomes in patients with large vessel occlusion undergoing EVT and enrolled patients from March 1, 2017, to August 12, 2019. The ESCAPE-NA1 trial was an international randomized clinical trial that recruited patients from 7 countries. Patients with EuroQol 5-dimension 5-level (EQ-5D-5L) index values at 90 days and survivors with complete domain scores were included in the current study. Data were analyzed from July to September 2023.

Exposure:

Hospital arrival to arterial puncture time and other time metrics.

Main Outcomes and Measures:

EQ-5D-5L index scores were calculated at 90 days using country-specific value sets. The association between time from hospital arrival to EVT arterial-access (door-to-puncture) and EQ-5D-5L index score, quality-adjusted life years, and visual analog scale (EQ-VAS) were evaluated using quantile regression, adjusting for age, sex, stroke severity, stroke imaging, wake-up stroke, alteplase, and nerinetide treatment and accounting for clustering by site. Using logistic regression, the association between door-to-puncture time and reporting no or slight symptoms (compared with moderate, severe, or extreme problems) was determined in each domain (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression) or across all domains. Time from stroke onset was also evaluated, and missing data were imputed in sensitivity analyses.

Results:

Among 1105 patients in the ESCAPE-NA1 trial, there were 1043 patients with EQ-5D-5L index values at 90 days, among whom 147 had died and were given a score of 0, and 1039 patients (mean [SD] age, 69.0 [13.7] years; 527 male [50.7%]) in the final analysis as 4 did not receive EVT. There were 896 survivors with complete domain scores at 90 days. There was a strong association between door-to-puncture time and EQ-5D-5L index score (increase of 0.03; 95% CI, 0.02-0.04 per 15 minutes of earlier treatment), quality-adjusted life years (increase of 0.29; 95% CI, 0.08-0.49 per 15 minutes of earlier treatment), and EQ-VAS (increase of 1.65; 95% CI, 0.56-2.72 per 15 minutes of earlier treatment). Each 15 minutes of faster door-to-puncture time was associated with higher probability of no or slight problems in each of 5 domains and all domains concurrently (range from 1.86%; 95% CI, 1.14-2.58 for pain or discomfort to 3.55%; 95% CI, 2.06-5.04 for all domains concurrently). Door-to-puncture time less than 60 minutes was associated higher odds of no or slight problems in each domain, ranging from odds ratios of 1.49 (95% CI, 1.13-1.95) for pain or discomfort to 2.59 (95% CI, 1.83-3.68) for mobility, with numbers needed to treat ranging from 7 to 17. Results were similar after multiple imputation of missing data and attenuated when evaluating time from stroke onset.

Conclusions and Relevance:

Results suggest that faster door-to-puncture EVT time was strongly associated with better health-related quality of life across all domains. These results support the beneficial impact of door-to-treatment speed on patient-reported outcomes and should encourage efforts to improve patient-centered care in acute stroke by optimizing in-hospital processes and workflows.

项与 Nerinetide 相关的新闻（医药）

2024-07-02

·药通社

脑卒中“一哥”丁苯酞或遇下一代王者

2024 CMC（CRO&MAH&CMO）博览会，将于8月15-16日在苏州国际博览中心C、D、E馆召开，内容涵盖前沿法规政策、MAH、改良型新药、吸入制剂、透皮制剂、中药、缓控释制剂、注射剂、原料药、辅料领域热点话题。仿制药立项思路和产品布局如今有何变化？以透皮给药平台为导向的产品立项思路如何？一键报名 · 见证合作！最近，脑卒中领域研发“先驱”南京宁丹再发重磅信息： 2024年6月27日，他们首次在CDE网站公示了注射用Y-3治疗急性缺血性卒中的三期临床研究情况。根据公开资料，ZL006-05（即Y-3）公开了结构式，很明显是两个片段成脂键的前药设计，再看看右边那个片段，有点似曾相识，没错，就是那个游离在中药和化药之间的分子：右莰醇（天然冰片）！谈到右莰醇，业内首先会想起先声药业的当家花旦：依达拉奉右莰醇小水针。南京宁丹与先声药业有着千丝万缕的关系。先声药业目前在研的依达拉奉右莰醇舌下片就是由南京宁丹合作研发的。竞争格局目前治疗脑卒中的销量扛把子产品是丁苯酞，哪怕是诊疗指南金标准药物溶栓类也望尘莫及！偌大的市场被石药集团独占。图 | 丁苯酞制剂年销量图源 | 药融云数据库先声药业面对如此巨大的市场，也早已开始了布局。对于同样对脑卒中有治疗效果的依达拉奉+右莰醇制剂，其中依达拉奉右莰醇注射用浓溶液20年就已获批上市，依达拉奉右莰醇舌下片于2023进行了申报。图 | 依达拉奉右莰醇注射用浓溶液年销量图源 | 药融云数据库届时先声药业预计将掌握依达拉奉右莰醇的两种剂型，市场格局将会有变革。目前依达拉奉右莰醇的两个剂型的三期临床试验文章均已发表，小水针第90天脑卒中mRS评分0~1分比例67.1% vs 59.0%，舌下片65% vs 54%。基于如此主观的量表，两个临床研究打出的分数是相当的漂亮，非常符合逻辑，如果把疗效从绝对数值排序（当然这样是很不严谨的，但是又会本能的这样去看）：依达拉奉右莰醇小水针＞依达拉奉右莰醇舌下片＞依达拉奉＞安慰剂这个成绩，无论是给投资人看还是学术推广，都堪称perfect！依达拉奉右莰醇的市场容量目前虽未达到丁苯酞的水平，但若孪生兄弟：依达拉奉右莰醇舌下片（Y-2）的批准上市，再由先声药业相当成熟的神经系统商业化团队推广，两种剂型双管齐下，中国脑卒中药物“一哥”丁苯酞表示压力很大！进一步布局基于以上两个三期临床试验也能得出一个结论：右莰醇增强疗效的作用是基本坐实了。故而想到将其接到另一个靶点药物上去申请核心化合物专利便也水到渠成，就有了开篇提到的Y-3。根据公开信息报道，Y-3的另外一个片段是靶向PSD-95，与国外正在三期临床试验中的药物Nerinetide同靶点，该药物一项三期临床研究ESCAPE-NA1显示其在非溶栓患者中疗效与安慰剂有显著差异，给了PSD-95靶点一线希望，但遗憾的是2023年公布的第二项三期临床研究ESCAPE-NEXT显示未优效于安慰剂。而背靠专业脑保护玩家先声药业的南京宁丹新药，前有双剂型的临床运营成功经验，后有右莰醇的功效继续加持，对Y-3的靶向研究势在必得。也正是看到依达拉奉右莰醇小水针运作如此成功，若新拥有这样一个神经保护剂，就相当于拥有了一台印钞机。康哲药业甚至都没有等到Y-3二期临床试验结果出来，就立马买下其中国的独家商业化推广权，外加股权投资。最后笔者大胆猜测：通过南京宁丹新药公开的研发管线资料和专利申请，公司专注于舌下给药技术和复方多靶点设计，除Y-2（依达拉奉右莰醇组合物）和Y-3（含右莰醇片段）外，Y-4、Y-5、Y-6和Y-8有可能都含有右莰醇或片段，成为超越丁苯酞的下一代王者。【题外话】笔者一直有个疑问：为什么脑保护剂国外做一个死一个，先声/宁丹/益诺依为什么做一个成一个？明明国内入组的脑卒中患者严重程度（NIHSS评分）更低（安慰剂效应更强），而且临床试验过程中难免会使用其他神药的干扰（毕竟受试者对安慰剂组的担忧和国人本能对输液的需求），再叠加各个中心主观评分的不一致性，脑保护临床试验阳性结果的难度可见一斑。在欧美等主流医学界对脑保护剂没有推荐之前，只能说是中国特色的存在。参考资料： Preclinical evaluation of ZL006-05, anew antistroke drug with fast-onset antidepressant and anxiolytic effects 《Edaravone dexborneol versus edaravone alone for the treatment of acute ischemic stroke: aphase III, randomized, double-blind,comparative trial.》《Sublingual Edaravone Dexborneol for the Treatment of Acute Ischemic Stroke: The TASTE-SL Randomized Clinical Trial》推荐阅读

临床3期上市批准临床成功

2024-03-18

·生物制药小编

停药仍能持续减肥

随着3月9日司美格鲁肽得到FDA批准用于辅助预防重大心血管事件，司美格鲁肽等GLP-1类减肥药物的跨界效果也得到了监管机构的认可。然而，这类减肥药物目前现阶段的数据表明，这些药物虽然有行之有效，但一旦停药反弹幅度也很大，且反弹过程中可能导致心血管方面的益处也可能因为反弹而恢复原样。既然减肥药能够跨界到心血管领域，那么其他领域的药物能不能跨界到肥胖呢？不仅可以，即便停药后，依然可以做到持续减肥。近日（3月1日），来自丹麦哥本哈根大学的诺和诺德基金会基础代谢研究中心在Science子刊Science Advances上发表了一篇论文。研究人员采用了之前只在神经病性疼痛和中风中进行开发的PSD-95和PICK1靶点，并试图用新方法将其运用在肥胖症上。NMDA受体和AMPA受体的崭新开发方式在过去的十年中，全基因组关联研究（GWAS）揭示了许多可能导致肥胖发病的生物学途径。在这些途径中，不少基因直接在大脑内富集/表达，在肥胖的遗传研究中，与α-氨基-3-羟基-5-甲基-4-异唑丙酸(AMPA)和n -甲基-d-天冬氨酸(NMDA)受体相关的谷氨酸能信号传导和突触后可塑性相关的基因尤其丰富，这表明谷氨酸能神经递质系统在调节能量平衡的稳态机制在肥胖症中发挥了重要作用。但问题在于，这两条途径的受体在整个中枢神经系统中普遍表达，强行去开发靶向药物很可能造成神经损伤。上游途径惹不起，那就只能从下游着手。因此，科学家们就试图去探索细胞内受体蛋白复合物的靶向，因为靶向蛋白质复合物就能够实现突触后受体信号的精确干扰。而AMPA和NMDA受体都会直接与细胞内支架蛋白相互作用，这些细胞内支架蛋白能够参与膜上谷氨酸受体的锚定和运输。支架蛋白中的许多又含有PDZ结构域。PDZ结构域（PDZ domain）是一种在多种蛋白质中发现的结构元件，它是蛋白质-蛋白质相互作用的重要模块。PDZ结构域得名于最初发现它的三种蛋白质：Postsynaptic density protein-95 (PSD-95)、Dlg1 ( discs large homolog 1) 和 Zonula occludens-1 (ZO-1)，每个蛋白质的名字首字母组成了“PDZ”。也就是说只要靶向含有PDZ结构域的蛋白质，就能够解决不能直接靶向受体的问题了，而这种含有PDZ结构域的支架蛋白就成为了众多中枢神经系统疾病的理想靶点。而此次该靶点就在肥胖症上得到开发。遗传筛选获得理想蛋白质为了确定肥胖治疗的药物靶点，研究人员寻找了至少由一个PDZ结构域组成的蛋白质，这些蛋白质已知参与谷氨酸能AMPA或NMDA受体的蛋白质相互作用。他们确定了六种符合这些标准的蛋白质:谷氨酸受体相互作用蛋白1（grip 1）、GRIP2、与C激酶1相互作用的蛋白（PICK1）、PSD-95。而下一轮筛选由遗传相关性展开，他们采用了UK Biobank（英国生物银行）的数据，并通过调查转录起始位点周围500 kb区域内的所有常染色体变异与体重指数（身体质量指数）和体脂百分比（BF%）的相关性，最终筛选获得了PSD-95和PICK1这两项与肥胖呈现出正相关的靶点。PSD-95抑制剂可降低小鼠体重其实之前就有PSD-95抑制剂NA-1差点成功上市，但临门一脚却因为主要临床不达终点而功败垂成。当时的适应症是心血管疾病。现在，丹麦的研究人员开发了一种二聚肽抑制剂UCCB 01-147，数据对照来看，与NA-1相比，UCCB 01-147以同等摩尔剂量更显著地降低了体重和食物摄入量，且这一降低并非由脱靶效应驱动。PICK1抑制剂可降低小鼠体重同样，研究人员开发了另外一种PICK1二聚肽抑制剂的脂质化变体mPD5，该抑制剂能够干扰AMPA受体的PICK1依赖性磷酸化。同样做到了以剂量依赖性地降低肥胖小鼠的体重。为了证明mPD5是通过PICK1抑制来实现肥胖降低的，因此研究人员用PICK1敲除小鼠进行对照。在高脂饮食喂养的PICK1敲除小鼠中，研究人员发现在DIO野生型同窝出生小鼠中观察到的mPD5降低体重和食物摄入量的作用在PICK1基因敲除小鼠中完全消失，这表明mPD5抑制食欲和减轻体重的作用确实是通过PICK1介导的。抑制剂的持久性对谷氨酸受体的药物干扰可以通过减少兴奋性神经传递、促进神经回路变化并可能引发持续的疾病缓解益处来诱导持久的神经可塑性效应。为了评估mPD5和UCCB01-147治疗的长期代谢效果，研究人员进行了为期13天的治疗研究，然后进行了为期29天的清除/体重恢复期。在这项研究中，两种化合物在13天的治疗期内都获得了显著的减肥益处。与先前的研究一致，两种化合物的体重减轻仅反映在体脂质量的减少上。值得注意的是，尽管两种PDZ结构域干扰化合物的半衰期在几分钟到几小时的范围内，体重减轻在治疗停止后持续约10天。治疗停止四周后，用mPD5治疗的小鼠仍然没有赶上溶媒对照组的体重，这表明PICK1干扰可能对体重有持久影响。在一项后续研究中，评估了mPD5对GLP-1受体激动剂利拉鲁肽的持续减肥效果。治疗停止后，mPD5治疗的小鼠在3天内体重持续下降，体重下降持续约8天。相反，利拉鲁肽治疗的小鼠在治疗停止后立即开始体重恢复，恢复速度比mPD5治疗的小鼠更快。到第35天，利拉鲁肽治疗的小鼠等于溶媒对照组的体重，而mPD5治疗的小鼠则保持显著低于溶媒对照组的体重。为了解决与利拉鲁肽治疗小鼠和mPD5治疗小鼠之间体重减轻差异相关的潜在混杂因素，研究人员还额外进行了一项研究，他们将mPD5治疗小鼠与一组进行热量限制以实现等效体重减轻的小鼠进行了比较。在停止热量限制和mPD5治疗后，各组的体重恢复立即出现差异。与之前的观察结果一致，mPD5治疗的小鼠在停药后体重恢复缓慢，但在恢复期第16天，两组小鼠已经的体重恢复程度已经达到一致。体重恢复的最初分离反映在热量限制组中强烈的反调节性摄食过度。相比之下，mPD5组恢复了与对照组小鼠相同的卡路里摄入量，没有表现出补偿性行为。这样的试验可能表明，假如一名肥胖症患者得到mPD5治疗后，体重减轻，但是停药后，即便他能够获得充足的饮食，也可能不会表征出补偿性暴饮暴食的情况。总结实际上，近年来，关于PSD-95靶点在如阿尔兹海默症，抑郁症等其他领域也展现出了一定可适用性，这也表明PSD-95抑制剂的潜在跨界应用，而PICK1抑制剂展现出了具有一定持久性治疗效果，考虑到目前是诺和诺德在主要资助这两款靶点的开发，可能引起一部分企业效仿。参考来源：https://www.science.org/doi/10.1126/sciadv.adg2636

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

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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	韩国	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
动脉瘤破裂	临床2期	美国	NoNO, Inc.	2015-11-01

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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


ESCAPE NA1-Trial (ISC2021)	N/A	脑卒中 \| 闭塞	1,105	Nerinetide	製齋願簾築願鑰築製醖(醖鏇淵選願積遞簾築蓋) = 構繭積憲壓獵醖糧淵廠範襯鑰壓糧選膚築蓋壓 (衊鏇鏇繭鹽壓繭憲選範 )	-	2021-03-01
				Placebo	製齋願簾築願鑰築製醖(醖鏇淵選願積遞簾築蓋) = 蓋壓獵築遞願選鹽鑰積範襯鑰壓糧選膚築蓋壓 (衊鏇鏇繭鹽壓繭憲選範 )
NCT00728182 (ENACT, CTgov)	临床2期	脑卒中 \| 动脉瘤	185	NA-1 (1 NA-1)	壓窪鬱鬱鏇襯觸製選膚(鬱鏇築襯淵鏇遞製憲夢) = 願膚鑰構衊憲鹹窪鏇願鹽願窪淵鹹鑰壓簾衊鏇 (醖製簾襯繭築築範築蓋, 衊鏇鹹窪選願構鹽顧夢 ~ 艱醖餘範壓膚選鏇鏇鹹) 更多	-	2013-10-17
				placebo (2 Placebo)	壓窪鬱鬱鏇襯觸製選膚(鬱鏇築襯淵鏇遞製憲夢) = 膚壓鹽廠糧鏇艱襯醖蓋鹽願窪淵鹹鑰壓簾衊鏇 (醖製簾襯繭築築範築蓋, 願壓願夢淵選顧製簾憲 ~ 餘壓壓選夢襯醖網襯蓋) 更多