Evidence map›Paper›PMID 36893823›Full record

ArticlePharmacological research2023

An MMP-9 exclusive neutralizing antibody attenuates blood-brain barrier breakdown in mice with stroke and reduces stroke patient-derived MMP-9 activity.

Yabin Ji, Qiang Gao, Yinzhong Ma, Fang Wang, Xixi Tan, Dengpan Song, Ruby L C Hoo, Zening Wang, Xin Ge, Hongjie Han and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pharmacological research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 2 pooled it
17.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 83 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 8 institutions in 3 countries.

Yabin JiInstitute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Qiang GaoInstitute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450001, China; Department of Neurosurgery, Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 100084, China.
Yinzhong MaInstitute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
Fang WangInstitute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450001, China.
Xixi TanDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Neurology, Yangjiang People's Hospital, Yangjiang 529500, China.
Dengpan SongInstitute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450001, China.
Ruby L C HooState Key Laboratory of Pharmaceutical Biotechnology, Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong 999077, China.
Zening WangDepartment of Chemical and Environmental Engineering, University of California, Riverside, CA 92521, USA.
Xin GeDepartment of Chemical and Environmental Engineering, University of California, Riverside, CA 92521, USA.
Hongjie HanDepartment of Neurosurgery, Pingdingshan Second People's Hospital, Pingdingshan 467000, China.
Fuyou GuoDepartment of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450001, China. Electronic address: chyou666@hotmail.com.
Junlei ChangInstitute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China. Electronic address: jl.chang@siat.ac.cn.
Shenzhen Institutes of Advanced Technology · CNFirst Affiliated Hospital of Zhengzhou University · CNUniversity of California, Riverside · USChinese Academy of Sciences · CNNanfang Hospital · CNPingdingshan University · CNTsinghua University · CNUniversity of Hong Kong · HK

Funding

Therapeutic Monoclonal Antibodies Inhibiting Proteases of Biomedical ImportanceR35GM141089 · NIGMS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI GE, XIN · 2021 to 2025
$2.0M
Structure-based design of camel-like human selective mAbs against MMPs in diseaseR01GM115672 · NIGMS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI GE, XIN · 2016 to 2020
$1.5M
NIGMS NIH HHS R01 GM115672NIGMS NIH HHS R35 GM141089
6 · The paper itself

Abstract

Rapid upregulation of matrix metalloproteinase 9 (MMP-9) leads to blood-brain barrier (BBB) breakdown following stroke, but no MMP-9 inhibitors have been approved in clinic largely due to their low specificities and side effects. Here, we explored the therapeutic potential of a human IgG monoclonal antibody (mAb), L13, which was recently developed with exclusive neutralizing specificity to MMP-9, nanomolar potency, and biological function, using mouse stroke models and stroke patient samples. We found that L13 treatment at the onset of reperfusion following cerebral ischemia or after intracranial hemorrhage (ICH) significantly reduced brain tissue injury and improved the neurological outcomes of mice. Compared to control IgG, L13 substantially attenuated BBB breakdown in both types of stroke model by inhibiting MMP-9 activity-mediated degradations of basement membrane and endothelial tight junction proteins. Importantly, these BBB-protective and neuroprotective effects of L13 in wild-type mice were comparable to Mmp9 genetic deletion and fully abolished in Mmp9 knockout mice, highlighting the in vivo target specificity of L13. Meanwhile, ex vivo co-incubation with L13 significantly neutralized the enzymatic activities of human MMP-9 in the sera of ischemic and hemorrhagic stroke patients, or in the peri-hematoma brain tissues from hemorrhagic stroke patients. Overall, we demonstrated that MMP-9 exclusive neutralizing mAbs constitute a potential feasible therapeutic approach for both ischemic and hemorrhagic stroke.

Indexed as

Brain IschemiaHemorrhagic StrokeStrokeAnimalsBlood-Brain BarrierHumansMatrix Metalloproteinase 9MiceMice, KnockoutMatrix Metalloproteinase 9Antibody therapyBlood-brain barrierIntracranial hemorrhageIschemic strokeMMP-9

Identifiers

PMID36893823
PMCPMC11934118
OpenAlexW4323353027

What OpenQuestion holds

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LicenceTDM
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.