{"id":2184,"date":"2022-05-23T10:19:50","date_gmt":"2022-05-23T01:19:50","guid":{"rendered":"https:\/\/bionauts.jp\/?p=2184"},"modified":"2024-07-22T11:11:59","modified_gmt":"2024-07-22T02:11:59","slug":"drug-repositioning-for-fibrosis-treatment","status":"publish","type":"post","link":"https:\/\/bionauts.jp\/?p=2184","title":{"rendered":"Drug Repositioning for Fibrosis Treatment"},"content":{"rendered":"<h3>Advantage and Core Benefit<\/h3>\n<ul>\n<li>Repositioning of patent-expired safety-proven drug reduces development cost and time.<\/li>\n<li>Theoretical effective dose, 2mg of losartan for 50kg patient much smaller than commercialized dosages avoids risk of hypotensive side-effect, as well as off-label use.<\/li>\n<li>Potentially multiple indications: liver, kidney, lung, etc. with novel mechanism of action.<\/li>\n<\/ul>\n<h3>Background and Technology<\/h3>\n<p>Angiotensin receptor blockers (ARBs) have been reported to be beneficial for liver fibrosis, but its mechanisms remain unclear. Also, ARB is contraindicated for patients with high risk of hypotension.<\/p>\n<p>Our researcher found that even ultralow dose ARB can alleviate liver fibrosis through mechano-transduction regulation. 0.5 mg\/kg\/day, theoretically equivalent to 0.04 mg\/kg\/day for human, Losartan administration interferes the expression of several mechano-transduction related molecules, and effectively alleviates liver fibrosis of model mice.<\/p>\n<p>This technology is potentially appliable for fibrosis of kidney, heart lung, stomach, intestine, skeletal muscles, as well as skin.<\/p>\n<h3>Data<\/h3>\n<ul>\n<li>Hydrostatic pressure-induced liver fibrosis mouse model was established by partial inferior vena cava ligation (IVCL). 8 week, 0.5 mg\/kg\/day losartan treatment reduced fibrosis (fig), attenuated upregulation of alpha-SMA, mechano-transduction related molecules; RhoA, ROCK1, p-MLC2.<\/li>\n<li>50 mmHg hydrostatic pressure imposed human hepatic stellate cell ex-vivo model confirmed effect of 10nM losartan for mechano-transduction response.<\/li>\n<li>Effect also confirmed in unilateral ureteral occlusion kidney fibrosis model.<\/li>\n<\/ul>\n<table style=\"border-collapse: collapse; width: 100%;\">\n<tbody>\n<tr>\n<td style=\"width: 100%;\"><img decoding=\"async\" loading=\"lazy\" class=\"aligncenter size-large wp-image-2193\" src=\"http:\/\/bionauts.jp\/wp-content\/uploads\/2022\/05\/91a7ef07bdf9837ab05e3e2bdab4f7ec-1024x319.png\" alt=\"\" width=\"840\" height=\"262\" srcset=\"https:\/\/bionauts.jp\/wp-content\/uploads\/2022\/05\/91a7ef07bdf9837ab05e3e2bdab4f7ec-1024x319.png 1024w, https:\/\/bionauts.jp\/wp-content\/uploads\/2022\/05\/91a7ef07bdf9837ab05e3e2bdab4f7ec-300x94.png 300w, https:\/\/bionauts.jp\/wp-content\/uploads\/2022\/05\/91a7ef07bdf9837ab05e3e2bdab4f7ec-768x239.png 768w, https:\/\/bionauts.jp\/wp-content\/uploads\/2022\/05\/91a7ef07bdf9837ab05e3e2bdab4f7ec.png 1097w\" sizes=\"(max-width: 709px) 85vw, (max-width: 909px) 67vw, (max-width: 1362px) 62vw, 840px\" \/><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<table style=\"border-collapse: collapse; width: 47.6738%;\">\n<tbody>\n<tr>\n<td style=\"width: 100%;\"><img decoding=\"async\" loading=\"lazy\" class=\"aligncenter size-full wp-image-2194\" src=\"http:\/\/bionauts.jp\/wp-content\/uploads\/2022\/05\/9f0d58cfc634b91158c972f0f79465c0.png\" alt=\"\" width=\"462\" height=\"350\" srcset=\"https:\/\/bionauts.jp\/wp-content\/uploads\/2022\/05\/9f0d58cfc634b91158c972f0f79465c0.png 462w, https:\/\/bionauts.jp\/wp-content\/uploads\/2022\/05\/9f0d58cfc634b91158c972f0f79465c0-300x227.png 300w\" sizes=\"(max-width: 462px) 85vw, 462px\" \/><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<h3>Patent and Publications<\/h3>\n<p>Patent: WO\/2023\/140350, pending in JP, US, EP.<br \/>\nJournal: American Journal of Physiology-Gastrointestinal and Liver Physiology, Vol. 322, No. 4\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 <a href=\"https:\/\/journals.physiology.org\/doi\/abs\/10.1152\/ajpgi.00238.2021\">\u00a0https:\/\/journals.physiology.org\/doi\/abs\/10.1152\/ajpgi.00238.2021<\/a><\/p>\n<h3>Researcher<\/h3>\n<p>Prof. Tao-Sheng Li, Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, Japan<\/p>\n<h3>Expectations<\/h3>\n<p>We are seeking a partner who will commercialize low dose ARBs as anti-fibrosis drug.<br \/>\nThe researcher is welcome for joint research for specific fibrotic disease.<\/p>\n<p>Project No.KJ-04320<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Only 1\/60 dose of anti-hypertensive alleviates fibrosis<\/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":[99,96],"other_than_medicine":[],"material":[],"engineering":[],"software_it":[],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts\/2184"}],"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=2184"}],"version-history":[{"count":14,"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts\/2184\/revisions"}],"predecessor-version":[{"id":3813,"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts\/2184\/revisions\/3813"}],"wp:attachment":[{"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2184"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2184"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2184"},{"taxonomy":"categories_of_inventions","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories_of_inventions&post=2184"},{"taxonomy":"disease_categories___indication","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fdisease_categories___indication&post=2184"},{"taxonomy":"asset_type","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fasset_type&post=2184"},{"taxonomy":"development_phase","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fdevelopment_phase&post=2184"},{"taxonomy":"medicine","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fmedicine&post=2184"},{"taxonomy":"other_than_medicine","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fother_than_medicine&post=2184"},{"taxonomy":"material","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fmaterial&post=2184"},{"taxonomy":"engineering","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fengineering&post=2184"},{"taxonomy":"software_it","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fsoftware_it&post=2184"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}