{"id":2306,"date":"2024-10-29T14:49:52","date_gmt":"2024-10-29T13:49:52","guid":{"rendered":"https:\/\/www.rmsb.u-bordeaux.fr\/fr\/?page_id=2306"},"modified":"2025-02-06T00:43:35","modified_gmt":"2025-02-05T23:43:35","slug":"projet-lpcbiomab","status":"publish","type":"page","link":"https:\/\/www.rmsb.u-bordeaux.fr\/fr\/projet-lpcbiomab\/","title":{"rendered":"projet LPCbioMab"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-page\" data-elementor-id=\"2306\" class=\"elementor elementor-2306\">\n\t\t\t\t<div class=\"elementor-element elementor-element-b14f960 e-grid e-con-boxed wpr-particle-no wpr-jarallax-no wpr-parallax-no wpr-sticky-section-no e-con e-parent\" data-id=\"b14f960\" data-element_type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t<div class=\"elementor-element elementor-element-71e641d elementor-widget elementor-widget-heading\" data-id=\"71e641d\" data-element_type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<style>\/*! elementor - v3.21.0 - 26-05-2024 *\/\n.elementor-heading-title{padding:0;margin:0;line-height:1}.elementor-widget-heading .elementor-heading-title[class*=elementor-size-]>a{color:inherit;font-size:inherit;line-height:inherit}.elementor-widget-heading .elementor-heading-title.elementor-size-small{font-size:15px}.elementor-widget-heading .elementor-heading-title.elementor-size-medium{font-size:19px}.elementor-widget-heading .elementor-heading-title.elementor-size-large{font-size:29px}.elementor-widget-heading .elementor-heading-title.elementor-size-xl{font-size:39px}.elementor-widget-heading .elementor-heading-title.elementor-size-xxl{font-size:59px}<\/style><h2 class=\"elementor-heading-title elementor-size-default\">Projet LPCBioMab<\/h2>\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-d7d15e0 e-grid e-con-boxed wpr-particle-no wpr-jarallax-no wpr-parallax-no wpr-sticky-section-no e-con e-parent\" data-id=\"d7d15e0\" data-element_type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t<div class=\"elementor-element elementor-element-eb47a15 elementor-widget elementor-widget-text-editor\" data-id=\"eb47a15\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<style>\/*! elementor - v3.21.0 - 26-05-2024 *\/\n.elementor-widget-text-editor.elementor-drop-cap-view-stacked .elementor-drop-cap{background-color:#69727d;color:#fff}.elementor-widget-text-editor.elementor-drop-cap-view-framed .elementor-drop-cap{color:#69727d;border:3px solid;background-color:transparent}.elementor-widget-text-editor:not(.elementor-drop-cap-view-default) .elementor-drop-cap{margin-top:8px}.elementor-widget-text-editor:not(.elementor-drop-cap-view-default) .elementor-drop-cap-letter{width:1em;height:1em}.elementor-widget-text-editor .elementor-drop-cap{float:left;text-align:center;line-height:1;font-size:50px}.elementor-widget-text-editor .elementor-drop-cap-letter{display:inline-block}<\/style>\t\t\t\t<p>Lanc\u00e9 en 2023, le projet LPCBioMab (<strong><u>ANR 2023-2027, port\u00e9 par le Dr G. Clofent-Sanchez, 271k<\/u><\/strong><strong><u>\u20ac)<\/u><\/strong> combine <strong><u>th\u00e9rapie et diagnostic de l\u2019ath\u00e9roscl\u00e9rose<\/u><\/strong><strong> au sein d\u2019un complexe lipoprot\u00e9ique<\/strong> (LPC).<\/p><p>Le c\u0153ur de ce projet repose sur la conception de mol\u00e9cules d\u2019HDL reconstitu\u00e9es ou HDL-like dans lesquelles seront incorpor\u00e9es, <strong>en tant qu\u2019agents th\u00e9rapeutiques<\/strong> <strong>de l\u2019ApoA1 fonctionnelle<\/strong> (pour ses propri\u00e9t\u00e9s biomim\u00e9tiques) <strong>et de <\/strong><strong>l&rsquo;acide linol\u00e9ique conjugue\u0301 (CLA)<\/strong>.<\/p><p>L&rsquo;apport d&rsquo;ApoA1 non oxyd\u00e9e vise \u00e0 restaurer localement l\u2019efflux du cholest\u00e9rol cellulaire et potentiellement \u00e0 induire un ph\u00e9notype anti-inflammatoire des MP au niveau des l\u00e9sions. Le CLA, en plus de ses propri\u00e9t\u00e9s immunor\u00e9gulatrices, pourrait ralentir la formation des cellules spumeuses en inhibant la phagocytose d&rsquo;oxLDL et en induisant les r\u00e9cepteurs ABCA1 et ABCG1 (impliqu\u00e9s dans l\u2019excr\u00e9tion du cholest\u00e9rol cellulaire via les HDL) <span style=\"color: #000000;\"><a style=\"color: #000000; text-decoration: underline;\" href=\"#_ftn1\" name=\"_ftnref1\">[1]<\/a>. <\/span><\/p><p><strong>Ces HDL-like seront coupl\u00e9es \u00e0 des AcHu anti-MP ath\u00e9rog\u00e8nes, ainsi qu\u2019\u00e0 des anticorps anti-ApoA1 oxyd\u00e9e propri\u00e9taires<\/strong> d\u00e9j\u00e0 test\u00e9s dans les plaques d\u2019ath\u00e9rome <a href=\"#_ftn2\" name=\"_ftnref2\">[2]<\/a> (en collaboration avec le Pr Venkataraman, CBST, VIT universit\u00e9, India), <strong>pour concentrer l&rsquo;effet th\u00e9rapeutique dans les zones vuln\u00e9rables<\/strong> des plaques. Les propri\u00e9t\u00e9s de ciblage et les effets ath\u00e9roprotecteurs (inhibition de la progression de l&rsquo;ath\u00e9roscl\u00e9rose et r\u00e9duction de l&rsquo;inflammation) seront \u00e9valu\u00e9s dans le mod\u00e8le animal Apoe<sup>-\/-<\/sup>. Pour le suivi de la th\u00e9rapie, une mol\u00e9cule HDL-like sans CLA charg\u00e9e avec un <strong>alliage de fer-platine<\/strong> sera d\u00e9velopp\u00e9 pour une d\u00e9tection par IRM.<\/p><p><span style=\"color: #000000;\"><a style=\"color: #000000;\" href=\"#_ftnref1\" name=\"_ftn1\">[1]<\/a> <\/span>Bruen, R., Fitzsimons, S. &amp; Belton, O. <em>Br J Clin Pharmacol. <\/em>2017 Jan;83(1):46-53.<\/p><p><a href=\"#_ftnref2\" name=\"_ftn2\"><\/a>[<u>2<\/u>] Lokeshwaran, K.<em> et al.<\/em> <em>J Immunol Methods . 2019 <\/em>Nov:474:112637.<\/p><p>\u00a0<\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-f1e8521 e-grid e-con-boxed wpr-particle-no wpr-jarallax-no wpr-parallax-no wpr-sticky-section-no e-con e-parent\" data-id=\"f1e8521\" data-element_type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t<div class=\"elementor-element elementor-element-3f3ec3c elementor-widget elementor-widget-image\" data-id=\"3f3ec3c\" data-element_type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<style>\/*! elementor - v3.21.0 - 26-05-2024 *\/\n.elementor-widget-image{text-align:center}.elementor-widget-image a{display:inline-block}.elementor-widget-image a img[src$=\".svg\"]{width:48px}.elementor-widget-image img{vertical-align:middle;display:inline-block}<\/style>\t\t\t\t\t\t\t\t\t\t<img fetchpriority=\"high\" decoding=\"async\" width=\"768\" height=\"461\" src=\"https:\/\/www.rmsb.u-bordeaux.fr\/wp-content\/uploads\/2024\/10\/image-pour-le-projet-LPCbioMab-768x461.png\" class=\"attachment-medium_large size-medium_large wp-image-2347\" alt=\"\" srcset=\"https:\/\/www.rmsb.u-bordeaux.fr\/wp-content\/uploads\/2024\/10\/image-pour-le-projet-LPCbioMab-768x461.png 768w, https:\/\/www.rmsb.u-bordeaux.fr\/wp-content\/uploads\/2024\/10\/image-pour-le-projet-LPCbioMab-300x180.png 300w, https:\/\/www.rmsb.u-bordeaux.fr\/wp-content\/uploads\/2024\/10\/image-pour-le-projet-LPCbioMab-1024x614.png 1024w, https:\/\/www.rmsb.u-bordeaux.fr\/wp-content\/uploads\/2024\/10\/image-pour-le-projet-LPCbioMab-1536x921.png 1536w, https:\/\/www.rmsb.u-bordeaux.fr\/wp-content\/uploads\/2024\/10\/image-pour-le-projet-LPCbioMab.png 1611w\" sizes=\"(max-width: 768px) 100vw, 768px\" \/>\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-521cbe8 e-grid e-con-boxed wpr-particle-no wpr-jarallax-no wpr-parallax-no wpr-sticky-section-no e-con e-parent\" data-id=\"521cbe8\" data-element_type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t<div class=\"elementor-element elementor-element-23a0837 elementor-widget elementor-widget-text-editor\" data-id=\"23a0837\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p><em><strong>Pr\u00e9sentation du consortium du projet <\/strong><strong>LPCBioMab<\/strong><\/em><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-3edbe40 e-grid e-con-boxed wpr-particle-no wpr-jarallax-no wpr-parallax-no wpr-sticky-section-no e-con e-parent\" data-id=\"3edbe40\" data-element_type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t<div class=\"elementor-element elementor-element-273b1b5 elementor-widget elementor-widget-text-editor\" data-id=\"273b1b5\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p>Les partenaires du projet incluent le Pr. C. Cabane (<strong>CBMN, <\/strong>Bordeaux) pour la production d\u2019ApoA1 Milano (variant d\u2019ApoA1 associe\u0301 a\u0300 une r\u00e9sistance aux maladies cardiovasculaires) et des AcHu anti-MP, le Pr P. Lesnik (<strong>UMR-S1166-ICAN, <\/strong>Paris) pour la reconstitution des particules HDL et l\u2019\u00e9tude de leurs propri\u00e9t\u00e9s, et le Dr S. Mornet (<strong>ICMCB<\/strong>, Bordeaux) pour son expertise dans le d\u00e9veloppement de nanoparticules multimodales (IRM, NIRF et microCT), et le <strong>CRMSB<\/strong> pour la s\u00e9lection d\u2019AcHu ciblant les MP ath\u00e9rog\u00e8nes. Pour d\u00e9marrer ce projet, nous disposions d\u2019ores et d\u00e9j\u00e0 de la s\u00e9lection d\u2019AcHu anti-Mox\/CE (cf. Projet (I)-PolAtheraDiag) r\u00e9alis\u00e9e par C. Borowczyk durant sa th\u00e8se (2017-2020). Depuis novembre 2023, M. Ragues a pu s\u00e9lectionner, parmi ces AcHu, ceux pr\u00e9sentant une s\u00e9quence VH-VL correcte, et montrant une interaction sp\u00e9cifique et reproductible, en ELISA puis en cytom\u00e9trie en flux, avec des MP spumeux g\u00e9n\u00e9r\u00e9s \u00e0 partir de donneurs diff\u00e9rents. Notre expertise en imagerie TPEF d\u00e9velopp\u00e9e dans le cadre du projet (II)-MEAP permettra d\u2019\u00e9valuer l\u2019effet th\u00e9rapeutique <em>in vitro<\/em> des HDL-like sur l\u2019immunor\u00e9gulation des MP (diminution de l\u2019AF NADH-like) et sur l\u2019efflux du cholest\u00e9rol (diminution de l\u2019AF NADH-like). L&rsquo;aboutissement de ce projet repr\u00e9senterait une avanc\u00e9e significative dans la lutte contre l&rsquo;ath\u00e9roscl\u00e9rose, en ouvrant la voie \u00e0 une approche th\u00e9ranostique novatrice.<\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-00f2f8f e-grid e-con-boxed wpr-particle-no wpr-jarallax-no wpr-parallax-no wpr-sticky-section-no e-con e-parent\" data-id=\"00f2f8f\" data-element_type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t<div class=\"elementor-element elementor-element-cc32fb4 elementor-widget elementor-widget-text-editor\" data-id=\"cc32fb4\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p>Cliquer sur les icones ci-dessous pour naviguer sur le site:<\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element 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decoding=\"async\" width=\"300\" height=\"111\" src=\"https:\/\/www.rmsb.u-bordeaux.fr\/wp-content\/uploads\/2025\/02\/Projet-4-300x111.png\" class=\"attachment-medium size-medium wp-image-3174\" alt=\"\" srcset=\"https:\/\/www.rmsb.u-bordeaux.fr\/wp-content\/uploads\/2025\/02\/Projet-4-300x111.png 300w, https:\/\/www.rmsb.u-bordeaux.fr\/wp-content\/uploads\/2025\/02\/Projet-4-768x283.png 768w, https:\/\/www.rmsb.u-bordeaux.fr\/wp-content\/uploads\/2025\/02\/Projet-4.png 811w\" sizes=\"(max-width: 300px) 100vw, 300px\" \/>\t\t\t\t\t\t\t\t<\/a>\n\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"<p>Projet LPCBioMab Lanc\u00e9 en 2023, le projet LPCBioMab (ANR 2023-2027, port\u00e9 par le Dr G. Clofent-Sanchez, 271k\u20ac) combine th\u00e9rapie et diagnostic de l\u2019ath\u00e9roscl\u00e9rose au sein d\u2019un complexe lipoprot\u00e9ique (LPC). Le c\u0153ur de ce projet repose sur la conception de mol\u00e9cules d\u2019HDL reconstitu\u00e9es ou HDL-like dans lesquelles seront incorpor\u00e9es, en tant qu\u2019agents th\u00e9rapeutiques de l\u2019ApoA1 fonctionnelle (pour ses propri\u00e9t\u00e9s biomim\u00e9tiques) et de l&rsquo;acide linol\u00e9ique conjugue\u0301 (CLA). L&rsquo;apport d&rsquo;ApoA1 non oxyd\u00e9e vise \u00e0 restaurer localement l\u2019efflux du cholest\u00e9rol cellulaire et potentiellement \u00e0 induire un ph\u00e9notype anti-inflammatoire des MP au niveau des l\u00e9sions. Le CLA, en plus de ses propri\u00e9t\u00e9s immunor\u00e9gulatrices, pourrait ralentir la formation des cellules spumeuses en inhibant la phagocytose d&rsquo;oxLDL et en induisant les r\u00e9cepteurs ABCA1 et ABCG1 (impliqu\u00e9s dans l\u2019excr\u00e9tion du cholest\u00e9rol cellulaire via les HDL) [1]. Ces HDL-like seront coupl\u00e9es \u00e0 des AcHu anti-MP ath\u00e9rog\u00e8nes, ainsi qu\u2019\u00e0 des anticorps anti-ApoA1 oxyd\u00e9e propri\u00e9taires d\u00e9j\u00e0 test\u00e9s dans les plaques d\u2019ath\u00e9rome [2] (en collaboration avec le Pr Venkataraman, CBST, VIT universit\u00e9, India), pour concentrer l&rsquo;effet th\u00e9rapeutique dans les zones vuln\u00e9rables des plaques. Les propri\u00e9t\u00e9s de ciblage et les effets ath\u00e9roprotecteurs (inhibition de la progression de l&rsquo;ath\u00e9roscl\u00e9rose et r\u00e9duction de l&rsquo;inflammation) seront \u00e9valu\u00e9s dans le mod\u00e8le animal Apoe-\/-. Pour le suivi de la th\u00e9rapie, une mol\u00e9cule HDL-like sans CLA charg\u00e9e avec un alliage de fer-platine sera d\u00e9velopp\u00e9 pour une d\u00e9tection par IRM. [1] Bruen, R., Fitzsimons, S. &amp; Belton, O. Br J Clin Pharmacol. 2017 Jan;83(1):46-53. [2] Lokeshwaran, K. et al. J Immunol Methods . 2019 Nov:474:112637. \u00a0 Pr\u00e9sentation du consortium du projet LPCBioMab Les partenaires du projet incluent le Pr. C. Cabane (CBMN, Bordeaux) pour la production d\u2019ApoA1 Milano (variant d\u2019ApoA1 associe\u0301 a\u0300 une r\u00e9sistance aux maladies cardiovasculaires) et des AcHu anti-MP, le Pr P. Lesnik (UMR-S1166-ICAN, Paris) pour la reconstitution des particules HDL et l\u2019\u00e9tude de leurs propri\u00e9t\u00e9s, et le Dr S. Mornet (ICMCB, Bordeaux) pour son expertise dans le d\u00e9veloppement de nanoparticules multimodales (IRM, NIRF et microCT), et le CRMSB pour la s\u00e9lection d\u2019AcHu ciblant les MP ath\u00e9rog\u00e8nes. Pour d\u00e9marrer ce projet, nous disposions d\u2019ores et d\u00e9j\u00e0 de la s\u00e9lection d\u2019AcHu anti-Mox\/CE (cf. Projet (I)-PolAtheraDiag) r\u00e9alis\u00e9e par C. Borowczyk durant sa th\u00e8se (2017-2020). Depuis novembre 2023, M. Ragues a pu s\u00e9lectionner, parmi ces AcHu, ceux pr\u00e9sentant une s\u00e9quence VH-VL correcte, et montrant une interaction sp\u00e9cifique et reproductible, en ELISA puis en cytom\u00e9trie en flux, avec des MP spumeux g\u00e9n\u00e9r\u00e9s \u00e0 partir de donneurs diff\u00e9rents. Notre expertise en imagerie TPEF d\u00e9velopp\u00e9e dans le cadre du projet (II)-MEAP permettra d\u2019\u00e9valuer l\u2019effet th\u00e9rapeutique in vitro des HDL-like sur l\u2019immunor\u00e9gulation des MP (diminution de l\u2019AF NADH-like) et sur l\u2019efflux du cholest\u00e9rol (diminution de l\u2019AF NADH-like). L&rsquo;aboutissement de ce projet repr\u00e9senterait une avanc\u00e9e significative dans la lutte contre l&rsquo;ath\u00e9roscl\u00e9rose, en ouvrant la voie \u00e0 une approche th\u00e9ranostique novatrice. 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