{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T15:34:01Z","timestamp":1774020841833,"version":"3.50.1"},"reference-count":49,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T00:00:00Z","timestamp":1703548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["JCYJ20210324101401004"],"award-info":[{"award-number":["JCYJ20210324101401004"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["JCYJ20210324115800003"],"award-info":[{"award-number":["JCYJ20210324115800003"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["SGLH20180625142404672"],"award-info":[{"award-number":["SGLH20180625142404672"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Adipocyte fatty acid\u2010binding protein (A\u2010FABP) exacerbates cerebral ischaemia injury by disrupting the blood\u2013brain barrier (BBB) through inducing expression of MMP\u20109. Circulating A\u2010FABP levels positively correlate with infarct size in stroke patients. We hypothesized that targeting circulating A\u2010FABP by a neutralizing antibody would alleviate ischaemic stroke outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Monoclonal antibodies (mAbs) against A\u2010FABP were generated using mouse hybridoma techniques. Binding affinities of a generated mAb named 6H2 towards various FABPs were determined using Biacore. Molecular docking studies were performed to characterize the 6H2\u2010A\u2010FABP complex structure and epitope. The therapeutic potential and safety of 6H2 were evaluated in mice with transient middle cerebral artery occlusion (MCAO) and healthy mice, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Replenishment of recombinant A\u2010FABP exaggerated the stroke outcome in A\u2010FABP\u2010deficient mice. 6H2 exhibited nanomolar to picomolar affinities to human and mouse A\u2010FABP, respectively, with minimal cross\u2010reactivities with heart and epidermal FABPs. 6H2 effectively neutralized JNK\/c\u2010Jun activation elicited by A\u2010FABP and reduced MMP\u20109 production in macrophages. Molecular docking suggested that 6H2 interacts with the \u201clid\u201d of the fatty acid binding pocket of A\u2010FABP, thus likely hindering the binding of its substrates. In mice with transient MCAO, 6H2 significantly attenuated BBB disruption, cerebral oedema, infarction, neurological deficits, and decreased mortality associated with reduced cytokine and MMP\u20109 production. Chronic 6H2 treatment showed no obvious adverse effects in healthy mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>These results establish circulating A\u2010FABP as a viable therapeutic target for ischaemic stroke, and provide a highly promising antibody drug candidate with high affinity and specificity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16282","type":"journal-article","created":{"date-parts":[[2023,11,11]],"date-time":"2023-11-11T02:38:31Z","timestamp":1699670311000},"page":"1238-1255","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Development of a therapeutic monoclonal antibody against circulating adipocyte fatty acid binding protein to treat ischaemic stroke"],"prefix":"10.1111","volume":"181","author":[{"given":"Boya","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacy, LKS Faculty of Medicine The 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