Des chercheurs de l\u2019Inserm et de l\u2019Universit\u00e9 d\u2019\u00c9vry Paris-Saclay, au sein d\u2019I-Stem (UMR861 Inserm\/Universit\u00e9 d\u2019\u00c9vry Paris-Saclay), ont mis au point une m\u00e9thode de \u00ab pharmacologie inverse \u00bb visant \u00e0 optimiser le rep\u00e9rage de nouvelles indications th\u00e9rapeutiques pour des m\u00e9dicaments d\u00e9j\u00e0 autoris\u00e9s. Cette approche consiste \u00e0 \u00e9tablir une cartographie d\u00e9taill\u00e9e des effets biologiques de ces m\u00e9dicaments sur des cellules saines (expression g\u00e9nique, fonctionnement cellulaire, r\u00e9ponse immunitaire), puis \u00e0 comparer ces signatures aux m\u00e9canismes observ\u00e9s dans des maladies donn\u00e9es, plut\u00f4t qu\u2019\u00e0 tester directement, une par une, des mol\u00e9cules sur des mod\u00e8les pathologiques.<\/p>\n
Les \u00e9quipes dirig\u00e9es par C\u00e9cile Martinat, avec le groupe de Sandrine Baghdoyan, ont appliqu\u00e9 cette m\u00e9thode \u00e0 un panel de 50 m\u00e9dicaments caract\u00e9ris\u00e9s par un large spectre d\u2019action et un profil d\u2019effets secondaires limit\u00e9. Les effets de ces m\u00e9dicaments sur l\u2019expression de l\u2019ensemble des g\u00e8nes ont \u00e9t\u00e9 mesur\u00e9s et compar\u00e9s. Plus de la moiti\u00e9 de ces compos\u00e9s se sont r\u00e9v\u00e9l\u00e9s modifier significativement l\u2019activit\u00e9 de g\u00e8nes, dont certains sont impliqu\u00e9s dans des pathologies.<\/p>\n
Les premiers r\u00e9sultats, publi\u00e9s dans la revue scientifique Stem Cell Reports, indiquent que la prazosine, m\u00e9dicament actuellement utilis\u00e9 dans le traitement de l\u2019hypertension art\u00e9rielle, pourrait pr\u00e9senter un int\u00e9r\u00eat th\u00e9rapeutique pour deux maladies neurod\u00e9g\u00e9n\u00e9ratives : la scl\u00e9rose lat\u00e9rale amyotrophique (SLA) et la d\u00e9g\u00e9n\u00e9rescence fronto-temporale (FTD). Dans certaines formes de ces maladies, des mutations du g\u00e8ne SQSTM1 entra\u00eenent une diminution de la prot\u00e9ine homonyme, impliqu\u00e9e dans l\u2019autophagie, m\u00e9canisme de nettoyage et de recyclage des composants cellulaires. Les chercheurs ont observ\u00e9 que la prazosine augmente l\u2019expression de cette prot\u00e9ine et r\u00e9active plusieurs voies mol\u00e9culaires li\u00e9es \u00e0 l\u2019autophagie, sugg\u00e9rant une possible restauration de ce m\u00e9canisme.<\/p>\n
Cette d\u00e9marche illustre un potentiel de repositionnement de m\u00e9dicaments existants pour des maladies neurod\u00e9g\u00e9n\u00e9ratives graves, en s\u2019appuyant sur des outils de biologie mol\u00e9culaire et de profilage d\u2019expression g\u00e9nique. Elle pourrait, \u00e0 terme, contribuer \u00e0 acc\u00e9l\u00e9rer l\u2019identification de nouvelles options th\u00e9rapeutiques, tout en s\u2019appuyant sur des mol\u00e9cules d\u00e9j\u00e0 connues en termes de tol\u00e9rance et de s\u00e9curit\u00e9, sous r\u00e9serve de confirmations ult\u00e9rieures. Le texte ne pr\u00e9cise toutefois ni calendrier, ni \u00e9tapes r\u00e9glementaires ou cliniques ult\u00e9rieures, ni impacts imm\u00e9diats sur les politiques de sant\u00e9.\u00a0(contenu r\u00e9sum\u00e9 en fran\u00e7ais par l’IA)\u200bLire la Suite<\/a>\u200b<\/p>","protected":false},"excerpt":{"rendered":" Des chercheurs de l\u2019Inserm et de l\u2019Universit\u00e9 d\u2019\u00c9vry Paris-Saclay, au sein d\u2019I-Stem (UMR861 Inserm\/Universit\u00e9 d\u2019\u00c9vry Paris-Saclay), ont mis au point une m\u00e9thode de \u00ab pharmacologie inverse \u00bb visant \u00e0 optimiser 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