{"id":2471,"date":"2022-11-14T14:17:54","date_gmt":"2022-11-14T05:17:54","guid":{"rendered":"https:\/\/bionauts.jp\/?p=2471"},"modified":"2022-11-14T14:19:24","modified_gmt":"2022-11-14T05:19:24","slug":"therapeutic-medicine-for-infectious-diseases-covid-19-targeting-the-vascular-barrier","status":"publish","type":"post","link":"https:\/\/bionauts.jp\/?p=2471","title":{"rendered":"Therapeutic Medicine for Infectious Diseases (COVID-19) Targeting the Vascular Barrier"},"content":{"rendered":"<h3>Advantage and Core Benefit<\/h3>\n<ul>\n<li>Reduced CLDN5 expression and vascular barrier disruption were observed in the lungs of COVID-19-infected patients<\/li>\n<li>Fluvastatin, an existing medicine that enhances CLDN5 expression, suppresses the disruption of the vascular barrier<\/li>\n<li>CLDN5 levels in blood were found to be decreased in critically ill patients, suggesting that CLDN5 may be a biomarker for the severity of illness.<\/li>\n<li>Screening of new small molecules using an original CLDN5 binding assay system<\/li>\n<li>Evaluation of new candidate compounds using an original model assay system for the disruption of the vascular barrier<\/li>\n<li>Already identified several antibodies and small molecules that restraint the vascular barrier<\/li>\n<\/ul>\n<h3>Background and Technology<\/h3>\n<p>Claudin-5 (CLDN5) is a cellular tight junction molecule, expressed in tight junctions such as vascular endothelial cells, mainly in microvascular endothelial cells of the lung and brain.<br \/>\nThe researchers in Japanese universities found that SARS-CoV-2 disrupts the vascular barrier by suppressing CLDN5 expression on vascular endothelial cells and attenuating adhesion between them, using a \u201crespiratory tract chip\u201d, an original model system of vascular barrier disruption. We found that CLDN5 expression was reduced in the lungs of patients with COVID-19 infection (see the right figure). Furthermore, Increasing CLDN5 expression in vascular endothelial cells by gene transfer or small molecule drug (fluvastatin) can suppress vascular endothelial barrier disruption caused by SARS-CoV-2. Based on these facts, the researchers propose that compounds targeting CLDN5 are a potential treatment for the severity and post-illness symptoms of infections, including COVID-19. We have several antibodies and small molecules that regulate the function and expression of CLDN5. In addition, research is underway on technologies such as increasing the permeability of the blood-brain barrier to deliver drugs into the brain, inhibiting the disruption of the vascular barrier caused by central nervous system disease.<\/p>\n<table style=\"border-collapse: collapse; width: 37.5%; height: 337px;\">\n<tbody>\n<tr>\n<td style=\"width: 60%;\"><img decoding=\"async\" loading=\"lazy\" width=\"216\" height=\"300\" class=\"size-medium wp-image-2488 alignleft\" src=\"http:\/\/bionauts.jp\/wp-content\/uploads\/2022\/11\/newDA-01670c-216x300.png\" srcset=\"https:\/\/bionauts.jp\/wp-content\/uploads\/2022\/11\/newDA-01670c-216x300.png 216w, https:\/\/bionauts.jp\/wp-content\/uploads\/2022\/11\/newDA-01670c.png 300w\" sizes=\"(max-width: 216px) 85vw, 216px\" \/><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>&nbsp;<\/p>\n<p><span style=\"font-size: 23px; font-weight: 900;\">Papers<\/span><\/p>\n<ul>\n<li><a href=\"https:\/\/www.science.org\/doi\/10.1126\/sciadv.abo6783\">Hashimoto et al., Science Advances (2022) 8(38)<\/a><\/li>\n<li><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/34602546\/\">Hashimoto et al., Biol Pharm Bull. (2021) 44(10):1380-1390<\/a><\/li>\n<\/ul>\n<h3>Researcher<\/h3>\n<p>Associate professor<br \/>\nYoshiaki OKADA (The University of Osaka)<\/p>\n<h3>Expectations<\/h3>\n<p>This study has confirmed the disruption of the vascular barrier by COVID-19 in respiratory tract chips and the lungs of COVID-19 patients. And CLDN5 enhancement by a small molecule is a promising strategy to treat for severity and post-illness symptoms of infections, including COVID-19. We are looking for collaborative partners to develop therapeutics and biomarker measurement systems based on this therapeutic concept using our proprietary assays and tools.<\/p>\n<p>&nbsp;<\/p>\n<p><span style=\"font-weight: 400;\">Project No: DA-01670c<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Small Molecule enhances Claudin-5 (CLDN5) function, which organizes tight junctions between vascular endothelial cells. And prevents vascular barrier disruption by pathogens, including COVID-19<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0},"categories":[1],"tags":[],"categories_of_inventions":[46],"disease_categories___indication":[],"asset_type":[],"development_phase":[],"medicine":[100,96],"other_than_medicine":[],"material":[],"engineering":[],"software_it":[],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts\/2471"}],"collection":[{"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=2471"}],"version-history":[{"count":33,"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts\/2471\/revisions"}],"predecessor-version":[{"id":2510,"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts\/2471\/revisions\/2510"}],"wp:attachment":[{"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2471"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2471"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2471"},{"taxonomy":"categories_of_inventions","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories_of_inventions&post=2471"},{"taxonomy":"disease_categories___indication","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fdisease_categories___indication&post=2471"},{"taxonomy":"asset_type","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fasset_type&post=2471"},{"taxonomy":"development_phase","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fdevelopment_phase&post=2471"},{"taxonomy":"medicine","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fmedicine&post=2471"},{"taxonomy":"other_than_medicine","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fother_than_medicine&post=2471"},{"taxonomy":"material","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fmaterial&post=2471"},{"taxonomy":"engineering","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fengineering&post=2471"},{"taxonomy":"software_it","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fsoftware_it&post=2471"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}