{"id":879,"date":"2012-02-14T18:46:31","date_gmt":"2012-02-14T16:46:31","guid":{"rendered":"http:\/\/slanedeti.sk\/cms\/liek-na-vylepsenie-mutacie-g551d-pri-cystickej-fibroze-2\/201202"},"modified":"2014-01-04T20:44:08","modified_gmt":"2014-01-04T19:44:08","slug":"liek-na-vylepsenie-mutacie-g551d-pri-cystickej-fibroze","status":"publish","type":"post","link":"https:\/\/slanedeti.sk\/cms\/liek-na-vylepsenie-mutacie-g551d-pri-cystickej-fibroze\/879","title":{"rendered":"Liek na vylep\u0161enie mut\u00e1cie G551D pri cystickej fibr\u00f3ze"},"content":{"rendered":"<p>Bol schv\u00e1len\u00fd prv\u00fd liek \u00fa\u010dinkuj\u00faci na prote\u00edn, ktor\u00fd je pr\u00ed\u010dinou ochorenia cystick\u00e1 fibr\u00f3za \u2013 prospech ale prinesie iba malej \u010dasti pacientov.<\/p>\n<p>V zaslepenej klinickej \u0161t\u00fadii pacienti a ani lek\u00e1ri nemaj\u00fa vedie\u0165, kto dost\u00e1va placebo a kto \u00fa\u010dinn\u00fa l\u00e1tku.\u00a0 Ale v pr\u00edpade \u0161t\u00fadie lieku Kalydeco (ivakaftor), ur\u010den\u00e9ho na lie\u010dbu cystickej fibr\u00f3zy, ktor\u00e9ho pou\u017eitie schv\u00e1lila 31. janu\u00e1ra 2012\u00a0 americk\u00e1 Food and Drug Administration, bolo pod\u013ea Drucy Borowitzovej niekedy \u013eahk\u00e9 vidie\u0165 rozdiel. \u201cMali sme v \u0161t\u00fadii dvoch bratov\u201c, hovor\u00ed Borowitzov\u00e1, pediatrick\u00e1 pulmologi\u010dka na New York State University v Buffalo. Po dvoch t\u00fd\u017ed\u0148och ich videla spolu vystupova\u0165 z v\u00fd\u0165ahu a hne\u010f bolo jasn\u00e9, kto z nich u\u017e\u00edva lie\u010divo. \u201cMlad\u0161\u00ed z bratov vyzeral by\u0165 zrazu silnej\u0161\u00ed\u201c. \u201cPripomenulo mi to zmenu vzh\u013eadu pacientov po transplant\u00e1cii p\u013e\u00fac\u201c, hovor\u00ed.<\/p>\n<p>Kalydeco, liek ktor\u00fd vyr\u00e1ba Vertex Pharmaceuticals z Cambridge, Massachusetts, USA je prv\u00fdm lie\u010divom, ktor\u00e9 ovplyv\u0148uje pr\u00ed\u010dinu ochorenia a nie iba jeho sympt\u00f3my. Tak sa po viac ako 20-tych rokoch nap\u013a\u0148a s\u013eub vedcov, o ktorom optimisticky hovorili po objave CFTR g\u00e9nu (sp\u00f4sobuj\u00faceho CF).<\/p>\n<p>\u201cToto je s\u013eubn\u00fd zvrat v CF lie\u010dbe\u201c, hovor\u00ed Matthew Reed, riadite\u013e Cystic Fibrosis Trust v Lond\u00fdne. \u201cMus\u00edme \u00eds\u0165, ale omnoho \u010falej, a\u017e pokia\u013e probl\u00e9m CF \u00faplne nevyrie\u0161ime\u201c. CFTR m\u00f4\u017ee ma\u0165 viac ako 1500 r\u00f4znych mut\u00e1cii, pri\u010dom Kalydeco \u00fa\u010dinkuje iba pri jednej \u2013 G551D, maj\u00fa ju 4% pacientov.<\/p>\n<p>CFTR prote\u00edn vytv\u00e1ra kan\u00e1l, ktor\u00fd umo\u017e\u0148uje chloridov\u00fdm i\u00f3nom prechod cez bunkov\u00e9 membr\u00e1ny, \u010do je d\u00f4le\u017eit\u00fd krok v produkcii hlienu, tr\u00e1viacich enz\u00fdmov a potu (obr\u00e1zok). U pacientov s G551D mut\u00e1ciou sa kan\u00e1l nedok\u00e1\u017ee spr\u00e1vnym sp\u00f4sobom otvori\u0165 a i\u00f3ny potom nem\u00f4\u017eu cez neho prejs\u0165. Pribli\u017ene 90 % \u013eud\u00ed s cystickou fibr\u00f3zou m\u00e1 in\u00fd typ mut\u00e1cie, F508del, ktor\u00e1 zapr\u00ed\u010di\u0148uje nespr\u00e1vne priestorov\u00e9 usporiadanie (folding) CFTR prote\u00ednov, n\u00e1sledkom \u010doho s\u00fa prote\u00edny degradovan\u00e9 a po\u010det kan\u00e1lov sa zni\u017euje. V oboch pr\u00edpadoch je nerovnov\u00e1ha i\u00f3nov pr\u00ed\u010dinou hust\u00e9ho a v\u00e4zk\u00e9ho hlienu, ktor\u00fd blokuje d\u00fdchacie cesty a u\u013eah\u010duje n\u00e1stup infekci\u00ed.<\/p>\n<p>Najprv bola my\u0161lienka, \u017ee lie\u010divo m\u00f4\u017ee napr\u00e1va\u0165 CF prote\u00edn nie moc presved\u010div\u00e1. V\u00e4\u010d\u0161ina lie\u010div \u00fa\u010dinkuje tak, \u017ee funkciu niektor\u00e9ho prote\u00ednu blokuj\u00fa, zv\u00e4\u010d\u0161a tak, \u017ee sa navia\u017eu na d\u00f4le\u017eit\u00fa \u010das\u0165 prote\u00ednu, \u010do vyvol\u00e1 \u0161truktur\u00e1lne zmeny a z\u00e1nik funkcie. \u201cRozbi\u0165 nie\u010do je jednoduch\u00e9\u201c, vrav\u00ed Eric Olson, ved\u00faci CF v\u00fdskumu vo Vertex Pharmaceuticals. \u201cOmnoho zlo\u017eitej\u0161ie je prote\u00edn opravi\u0165\u201c.<\/p>\n<p>Na horizonte sa v\u0161ak objavuj\u00fa aj lieky pre \u010fal\u0161ie CF mut\u00e1cie. \u010eal\u0161ou sk\u00famanou molekulou Vertexu je VX-809, ktor\u00e1 zrejme chr\u00e1ni prote\u00edny pri mut\u00e1cii F508del pred degrad\u00e1ciou. U\u017e sa uskuto\u010d\u0148uj\u00fa klinick\u00e9 sk\u00fa\u0161ky spolu s Kalydeco, ktor\u00e9 maj\u00fa zisti\u0165 \u010di VX-809 pom\u00f4\u017ee udr\u017ea\u0165 CFTR v bunkov\u00fdch membr\u00e1nach a Kalydeco by ich n\u00e1sledne pom\u00e1halo sfunk\u010dni\u0165. Minul\u00fd rok Vertex ozn\u00e1mil prv\u00e9 v\u00fdsledky, pod\u013ea ktor\u00fdch t\u00e1to kombinovan\u00e1 terapia zn\u00ed\u017eila obsah chloridov v pote \u2013 \u010do je znak na pos\u00fadenie funk\u010dnosti CFTR.\u00a0 Ale zatia\u013e \u010do Kalydeco zn\u00ed\u017eilo chloridy v pote u pacientov s G551D na polovicu, kombinovan\u00e1 terapia viedla iba k zn\u00ed\u017eeniu o 13% u t\u00fdch pacientov \u010do maj\u00fa mut\u00e1ciu F508del. Pod\u013ea Borowitzovej m\u00f4\u017ee by\u0165 pr\u00ed\u010dinou to, \u017ee d\u00e1vka lie\u010diva, ktor\u00e1 bola pou\u017eit\u00e1 v klinickej \u0161t\u00fadii nebola dostato\u010dne vysok\u00e1. V s\u00fa\u010dasnosti prebieha \u010fal\u0161ia klinick\u00e1 \u0161t\u00fadia s vy\u0161\u0161ou d\u00e1vkou, pri\u010dom v\u00fdsledky by mali by\u0165 k dispoz\u00edcii po\u010das tohto roka.<\/p>\n<p>Popritom spolo\u010dnos\u0165 PTC Therapeutics z New Plainfield v New Jersey, USA vyv\u00edja lie\u010dbu, ktor\u00e1 by s\u00fa\u010dasne ovplyv\u0148ovala viacero mut\u00e1cii, t\u00fdm \u017ee by zastavila CFTR proteosynt\u00e9zu a vzniknut\u00e9 prote\u00edny by nemali norm\u00e1lnu d\u013a\u017eku. Toto lie\u010divo \u2013 ataluren, je v pokro\u010dil\u00fdch \u0161t\u00e1di\u00e1ch klinick\u00e9ho v\u00fdskumu, pri\u010dom v\u00fdsledky by mali by\u0165 zn\u00e1me v priebehu tohto roka. Niektor\u00e9 in\u0161tit\u00facie vo Ve\u013ekej Brit\u00e1nii spolupracuj\u00fa s Americkou biotechnologickou spolo\u010dnos\u0165ou Genzyme z Cambridge na v\u00fdskume g\u00e9novej terapie, ktor\u00e1 by mohla zabezpe\u010di\u0165 expresiu norm\u00e1lneho CFTR prote\u00ednu. Predpoklad\u00e1 sa \u017ee v bl\u00edzkej dobe bud\u00fa v Brit\u00e1nii pre tento v\u00fdskum schv\u00e1len\u00e9 \u010fal\u0161ie \u0161t\u00fadie.<\/p>\n<p>Cystic Fibrosis Foundation (CFF) s\u00eddliaca v Bethsede v Marylande dlhodobo napom\u00e1ha v\u00fdvoju nov\u00fdch lie\u010div.\u00a0 Podporuje tie\u017e \u010fal\u0161\u00ed projekt firmy Genzyme ako tie\u017e projekt so spolo\u010dnos\u0165ou Pfizer so s\u00eddlom v New Yorku, ktor\u00e1 ned\u00e1vno odk\u00fapila FoldRx, firmu z Cambridge vyv\u00edjaj\u00facu lie\u010dbu pri ochoreniach zapr\u00ed\u010dinen\u00fdch \u0161truktur\u00e1lnymi poruchami (foldingom) prote\u00ednov. CFF d\u00fafa, \u017ee nov\u00e9 v\u00fdskumn\u00e9 technol\u00f3gie \u2013 ako napr\u00edklad testovanie liekov na bunkov\u00fdch kult\u00farach z\u00edskan\u00fdch od CF pacientov bud\u00fa efekt\u00edvnej\u0161ie ako s\u00fa\u010dasn\u00e9 testy na bunkov\u00fdch kult\u00farach potkanov.<\/p>\n<p>Napriek posledn\u00fdm \u00faspechom, vedci a pacienti predpokladaj\u00fa, \u017ee st\u00e1le bude asi potrebn\u00e1 kombin\u00e1cia viacer\u00fdch pr\u00edstupov, vzh\u013eadom na mnohostrann\u00fd dosah ochorenia. Ke\u010f bol prv\u00fd kr\u00e1t klonovan\u00fd CFTR g\u00e9n \u201cboli\u00a0 sme naivn\u00ed, ke\u010f sme si mysleli, \u017ee komplexn\u00e9 genetick\u00e9 choroby bude jednoduch\u00e9 lie\u010di\u0165\u201c prizn\u00e1va Jack Riodan, biochemik z University of South Carolina v Chappel Hill, ktor\u00fd bol s\u00fa\u010das\u0165ou t\u00edmu ktor\u00fd objavil CFTR. \u201cMysleli sme si, \u017ee sme k\u00fasok od objavu, ktor\u00fd v\u0161etko vyrie\u0161i, ale \u010d\u00edm viac vieme o CF, t\u00fdm sme vo vyjadrovan\u00ed opatrnej\u0161\u00ed\u201c.<\/p>\n<h4><strong>Ako lie\u010divo otvor\u00ed chloridov\u00fd kan\u00e1l<br \/>\n<\/strong><\/h4>\n<p>G\u00e9n ktor\u00fd je pri CF mutovan\u00fd, ak funguje norm\u00e1lne k\u00f3duje chloridov\u00fd kan\u00e1l, ktor\u00fd umo\u017e\u0148uje i\u00f3nom prechod cez bunkov\u00fa membr\u00e1nu a tak zabezpe\u010duje vytvori\u0165 ochrann\u00fa vrstvu tekut\u00e9ho hlienu.<\/p>\n<div style=\"text-align: center;\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter\" style=\"border: 0px; margin-top: 20px; margin-bottom: 20px;\" title=\"201202141822_obr1\" alt=\"201202141822_obr1\" src=\"https:\/\/slanedeti.sk\/cms\/picture_migration\/201202141822_obr1.jpg\" width=\"400\" height=\"322\" border=\"0\" \/><\/div>\n<p>Nov\u00e9 lie\u010divo napr\u00e1va \u00fa\u010dinky zriedkavej mut\u00e1cie G551D, ktor\u00e1 zabra\u0148uje spr\u00e1vnemu otvoreniu chloridov\u00e9ho kan\u00e1la a zapr\u00ed\u010di\u0148uje vznik hust\u00e9ho hlienu, ktor\u00fd u\u013eah\u010duje bakteri\u00e1lne infekcie.<\/p>\n<div style=\"text-align: center;\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter\" style=\"border: 0px; margin-top: 20px; margin-bottom: 20px;\" title=\"201202141823_obr2\" alt=\"201202141823_obr2\" src=\"https:\/\/slanedeti.sk\/cms\/picture_migration\/201202141823_obr2.jpg\" width=\"400\" height=\"322\" border=\"0\" \/><\/div>\n<p>V\u00e4\u010d\u0161ina \u013eud\u00ed s cystickou fibr\u00f3zou m\u00e1 mut\u00e1ciu F508del, ktor\u00e1 ovplvy\u0148uje priestorov\u00e9 usporiadanie CFTR proteinu a zni\u017euje po\u010det kan\u00e1lov.<\/p>\n<div style=\"text-align: center;\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter\" style=\"border: 0px; margin-top: 20px; margin-bottom: 20px;\" title=\"201202141823_obr3\" alt=\"201202141823_obr3\" src=\"https:\/\/slanedeti.sk\/cms\/picture_migration\/201202141823_obr3.jpg\" width=\"400\" height=\"331\" border=\"0\" \/><\/div>\n<p><em>Heidi Ledfort<br \/>\nNature.com<br \/>\n7. Febru\u00e1ra 2012<br \/>\n<\/em><em>P\u00f4vodn\u00fd \u010dl\u00e1nok: <a href=\"http:\/\/www.nature.com\/news\/drug-bests-cystic-fibrosis-mutation-1.9983?WT.mc_id=FBK_NPG\">nature.com<br \/>\n<\/a><\/em><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Bol schv&aacute;len&yacute; prv&yacute; liek &uacute;&#269;inkuj&uacute;ci na prote&iacute;n, ktor&yacute; je pr&iacute;&#269;inou ochorenia cystick&aacute; fibr&oacute;za &ndash; prospech ale prinesie iba malej &#269;asti pacientov. V zaslepenej klinickej &scaron;t&uacute;dii pacienti a ani lek&aacute;ri nemaj&uacute; vedie&#357;, kto dost&aacute;va placebo a kto &uacute;&#269;inn&uacute; l&aacute;tku.&nbsp; Ale v &hellip; <a href=\"https:\/\/slanedeti.sk\/cms\/liek-na-vylepsenie-mutacie-g551d-pri-cystickej-fibroze\/879\">Continued<\/a><\/p>\n","protected":false},"author":7,"featured_media":1214,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"kt_blocks_editor_width":"","footnotes":""},"categories":[3],"tags":[210,185],"class_list":["post-879","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-lieky-a-liecba","tag-lieky","tag-mutacia-g551d"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.5 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Liek na vylep\u0161enie mut\u00e1cie G551D pri cystickej fibr\u00f3ze - Slan\u00e9 deti<\/title>\n<meta name=\"description\" content=\"Bol schv\u00e1len\u00fd prv\u00fd liek \u00fa\u010dinkuj\u00faci na prote\u00edn, ktor\u00fd je pr\u00ed\u010dinou ochorenia cystick\u00e1 fibr\u00f3za \u2013 prospech, ale prinesie iba malej \u010dasti pacientov.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/slanedeti.sk\/cms\/liek-na-vylepsenie-mutacie-g551d-pri-cystickej-fibroze\/879\" \/>\n<meta property=\"og:locale\" content=\"sk_SK\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Liek na vylep\u0161enie mut\u00e1cie G551D pri cystickej fibr\u00f3ze - 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