Srpkovit\u00e1 an\u00e9mie z\u016fstala po dlouhou dobu ni\u010div\u00fdm d\u011bdi\u010dn\u00fdm onemocn\u011bn\u00edm, kter\u00e9 ne\u00fam\u011brn\u011b postihuje komunity v subsaharsk\u00fdch zem\u00edch a v Indii. Po desetilet\u00ed pacienti sn\u00e1\u0161eli cykly nesnesiteln\u00fdch bolest\u00ed a t\u011b\u017ek\u00e9 \u00fanavy, ani\u017e by vid\u011bli nad\u011bji na skute\u010dn\u00e9 uzdraven\u00ed. Tento obr\u00e1zek se v\u0161ak dramaticky zm\u011bnil. Po letech pe\u010dliv\u00e9ho genetick\u00e9ho v\u00fdzkumu se v\u011bdc\u016fm poda\u0159ilo odhalit mechanismus, kter\u00fd umo\u017e\u0148uje funk\u010dn\u00ed vyl\u00e9\u010den\u00ed nemoci t\u00edm, \u017ee nut\u00ed t\u011blo produkovat zdrav\u00e9 krvinky.<\/p>\n
Jako uzn\u00e1n\u00ed tohoto transforma\u010dn\u00edho objevu cena za pr\u016flom v \u017eivotn\u00edch v\u011bd\u00e1ch * * ud\u011blila<\/strong> 3 miliony dolar\u016f * * * Dr. sve Lay Thein a Dr. Stuart Orkin. Jejich pr\u00e1ce odhalila specifick\u00fd genetick\u00fd “vyp\u00edna\u010d”, kter\u00fd aktivac\u00ed umo\u017e\u0148uje t\u011blu obej\u00edt vadn\u00e9 geny zodpov\u011bdn\u00e9 za srpkovitou an\u00e9mii a beta thalassemii.<\/p>\n Abychom pochopili podstatu pr\u016flomu, je d\u016fle\u017eit\u00e9 pod\u00edvat se na to, jak se krev u \u010dlov\u011bka vyv\u00edj\u00ed. V d\u011bloze lid\u00e9 produkuj\u00ed * * fet\u00e1ln\u00ed hemoglobin * * – protein, kter\u00fd je vysoce \u00fa\u010dinn\u00fd p\u0159i extrakci kysl\u00edku z krevn\u00edho ob\u011bhu matky. Ihned po narozen\u00ed t\u011blo p\u0159irozen\u011b zastav\u00ed jeho produkci a p\u0159epne na dosp\u011bl\u00fd hemoglobin<\/strong>.<\/p>\n U lid\u00ed se srpkovitou an\u00e9mi\u00ed nebo beta thalassemi\u00ed je dosp\u011bl\u00fd hemoglobin bu\u010f zdeformovan\u00fd, nebo nedostate\u010dn\u00fd, co\u017e vede k tvorb\u011b charakteristick\u00fdch srpkovit\u00fdch \u010derven\u00fdch krvinek, kter\u00e9 ucp\u00e1vaj\u00ed c\u00e9vy a zp\u016fsobuj\u00ed bolest. Fet\u00e1ln\u00ed hemoglobin v\u0161ak z\u016fst\u00e1v\u00e1 pln\u011b schopen p\u0159en\u00e1\u0161et kysl\u00edk po cel\u00fd \u017eivot. Jedinou p\u0159ek\u00e1\u017ekou bylo, \u017ee v\u011bdci nev\u011bd\u011bli, jak udr\u017eet v\u00fdrobn\u00ed linku fet\u00e1ln\u00edho hemoglobinu aktivn\u00ed po narozen\u00ed.<\/p>\n Kritick\u00fdm objevem byla identifikace genu * * BCL11A**. Tento gen p\u016fsob\u00ed jako supresor a aktivn\u011b vyp\u00edn\u00e1 produkci fet\u00e1ln\u00edho hemoglobinu, jak rosteme. Orkin a Taine si uv\u011bdomili, \u017ee pokud dok\u00e1\u017eou deaktivovat BCL11A, mohou tla\u010dit t\u011blo k pokra\u010dov\u00e1n\u00ed ve v\u00fdrob\u011b zdrav\u00e9ho fet\u00e1ln\u00edho hemoglobinu a \u00fa\u010dinn\u011b neutralizovat \u00fa\u010dinky onemocn\u011bn\u00ed.<\/p>\n Cesta k tomuto objevu nebyla p\u0159\u00edm\u00e1, ale byla v\u00fdsledkem dvou vz\u00e1jemn\u011b se dopl\u0148uj\u00edc\u00edch v\u00fdzkumn\u00fdch p\u0159\u00edstup\u016f, kter\u00e9 trvaly v\u00edce ne\u017e dv\u011b desetilet\u00ed.<\/p>\n ** P\u0159\u00edstup Dr. Teina: sledov\u00e1n\u00ed rodinn\u00fdch lini\u00ed V\u0161iml si, \u017ee pacienti s m\u00edrn\u011bj\u0161\u00edmi formami onemocn\u011bn\u00ed m\u011bli \u010dasto p\u0159irozen\u011b vysok\u00e9 hladiny fet\u00e1ln\u00edho hemoglobinu. Aby Tane na\u0161el genetickou p\u0159\u00ed\u010dinu, odjel do Malawi, kde identifikoval velkou multidisciplin\u00e1rn\u00ed rodinu s neobvykle lehk\u00fdmi p\u0159\u00edpady onemocn\u011bn\u00ed. Po studiu 210 lid\u00ed po dobu sedmi generac\u00ed jeho t\u00fdm vystopoval rys do konkr\u00e9tn\u00ed genetick\u00e9 oblasti. V\u00fdzkum asociac\u00ed v cel\u00e9m genomu nakonec pouk\u00e1zal na * * bcl11a * * jako regul\u00e1tor zodpov\u011bdn\u00fd za tuto variaci a potvrdil ji jako \u017eivotaschopn\u00fd terapeutick\u00fd c\u00edl.<\/p>\n ** P\u0159\u00edstup Dr. Orkin: in\u017een\u00fdrstv\u00ed l\u00e9\u010dby** Tento d\u016fkaz konceptu prok\u00e1zal, \u017ee \u00fa\u010dinky na jeden gen jsou dostate\u010dn\u00e9 k vy\u0159e\u0161en\u00ed probl\u00e9mu onemocn\u011bn\u00ed. N\u00e1stup technologie pro \u00fapravu gen\u016f * * CRISPR * * kr\u00e1tce pot\u00e9 poskytl p\u0159esn\u00fd n\u00e1stroj pot\u0159ebn\u00fd k p\u0159ekladu tohoto my\u0161\u00edho modelu do lidsk\u00e9 terapie.<\/p>\n Teoretick\u00fd pr\u016flom se stal klinickou realitou. V roce 2023 byly schv\u00e1leny prvn\u00ed terapie zalo\u017een\u00e9 na \u00faprav\u011b gen\u016f pro srpkovitou an\u00e9mii: Casgevy<\/strong> (od Vertex Pharmaceuticals a CRISPR Therapeutics) a *** Lyfgenia* * (od bluebird bio\/Genetix Biotherapeutics).<\/p>\n Prvn\u00ed v\u00fdsledky klinick\u00fdch studi\u00ed byly transforma\u010dn\u00ed. “D\u0159\u00edve to byla miserably nemoc… Po l\u00e9\u010db\u011b dostanou nov\u00fd \u017eivot, ” poznamenal doktor Orkin a zd\u016fraznil hlubok\u00fd dopad na schopnost pacient\u016f pracovat a \u017e\u00edt norm\u00e1ln\u011b.<\/p>\n<\/blockquote>\n Navzdory l\u00e9ka\u0159sk\u00e9mu triumfu z\u016fst\u00e1vaj\u00ed zna\u010dn\u00e9 bari\u00e9ry p\u0159\u00edstupu. Sou\u010dasn\u00e9 schv\u00e1len\u00e9 terapie jsou** ex vivo * * l\u00e9\u010dby, co\u017e znamen\u00e1, \u017ee vy\u017eaduj\u00ed: Tento proces je fyzicky vy\u010derp\u00e1vaj\u00edc\u00ed, logisticky n\u00e1ro\u010dn\u00fd a mimo\u0159\u00e1dn\u011b drah\u00fd, stoj\u00ed od 2 do 3 milion\u016f dolar\u016f na pacienta<\/strong>. V d\u016fsledku toho jsou tyto l\u00e9\u010dby v sou\u010dasn\u00e9 dob\u011b nedostupn\u00e9 pro populaci v subsaharsk\u00fdch zem\u00edch a v Indii, kter\u00e9 nesou nejv\u011bt\u0161\u00ed z\u00e1t\u011b\u017e onemocn\u011bn\u00ed.<\/p>\n Uzn\u00e1n\u00edm t\u011bchto omezen\u00ed v\u011bdeck\u00e1 komunita p\u0159ech\u00e1z\u00ed na \u0159e\u0161en\u00ed nov\u00e9 generace. Oba l\u00e9ka\u0159i, Taine a Orkin, se nyn\u00ed zam\u011b\u0159uj\u00ed na terapii mal\u00fdmi molekulami<\/strong> \u2014 l\u00e9ky, kter\u00e9 lze u\u017e\u00edvat jako pilulku, sp\u00ed\u0161e ne\u017e aby vy\u017eadovaly komplexn\u00ed \u00fapravu gen\u016f.<\/p>\n Zat\u00edmco sou\u010dasn\u00e9 genov\u00e9 terapie nab\u00edzej\u00ed silnou l\u00e9\u010dbu pro ty, kte\u0159\u00ed k nim maj\u00ed p\u0159\u00edstup, kone\u010dn\u00fdm c\u00edlem je vyvinout cenov\u011b dostupn\u00e9 a dostupn\u00e9 l\u00e9\u010dby, kter\u00e9 mohou oslovit pacienty po cel\u00e9m sv\u011bt\u011b. Objev BCL11A poskytl mapu; dal\u0161\u00edm krokem je vytvo\u0159en\u00ed vozidel, kter\u00e1 budou schopna dodat tento l\u00e9k do ka\u017ed\u00e9ho koutu planety.<\/p>\n Z\u00e1v\u011br<\/strong> Srpkovit\u00e1 an\u00e9mie z\u016fstala po dlouhou dobu ni\u010div\u00fdm d\u011bdi\u010dn\u00fdm onemocn\u011bn\u00edm, kter\u00e9 ne\u00fam\u011brn\u011b postihuje komunity v subsaharsk\u00fdch zem\u00edch a v Indii. Po desetilet\u00ed pacienti sn\u00e1\u0161eli cykly nesnesiteln\u00fdch bolest\u00ed a t\u011b\u017ek\u00e9 \u00fanavy, ani\u017e by vid\u011bli nad\u011bji na skute\u010dn\u00e9 uzdraven\u00ed. Tento obr\u00e1zek se v\u0161ak dramaticky zm\u011bnil. Po letech pe\u010dliv\u00e9ho genetick\u00e9ho v\u00fdzkumu se v\u011bdc\u016fm poda\u0159ilo odhalit mechanismus, kter\u00fd umo\u017e\u0148uje funk\u010dn\u00ed […]<\/p>\n","protected":false},"author":1,"featured_media":7739,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"tdm_status":"","tdm_grid_status":""},"categories":[1],"tags":[],"amp_enabled":true,"_links":{"self":[{"href":"https:\/\/www.schooler.org.ua\/cs\/wp-json\/wp\/v2\/posts\/7740"}],"collection":[{"href":"https:\/\/www.schooler.org.ua\/cs\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.schooler.org.ua\/cs\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.schooler.org.ua\/cs\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.schooler.org.ua\/cs\/wp-json\/wp\/v2\/comments?post=7740"}],"version-history":[{"count":0,"href":"https:\/\/www.schooler.org.ua\/cs\/wp-json\/wp\/v2\/posts\/7740\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.schooler.org.ua\/cs\/wp-json\/wp\/v2\/media\/7739"}],"wp:attachment":[{"href":"https:\/\/www.schooler.org.ua\/cs\/wp-json\/wp\/v2\/media?parent=7740"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.schooler.org.ua\/cs\/wp-json\/wp\/v2\/categories?post=7740"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.schooler.org.ua\/cs\/wp-json\/wp\/v2\/tags?post=7740"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}Biologick\u00fd kl\u00ed\u010d: probuzen\u00ed fet\u00e1ln\u00edho hemoglobinu<\/h3>\n
Od klinick\u00fdch pozorov\u00e1n\u00ed ke genetick\u00e9mu objevu<\/h3>\n
\nPr\u00e1ce Dr. Teina za\u010dala klamn\u011b jednoduchou klinickou ot\u00e1zkou: <\/em> pro\u010d maj\u00ed n\u011bkte\u0159\u00ed pacienti s beta talas\u00e9mi\u00ed p\u0159\u00edznaky remarkably m\u00edrn\u00e9, zat\u00edmco jin\u00ed vy\u017eaduj\u00ed celo\u017eivotn\u00ed krevn\u00ed transfuze?<\/em> <\/p>\n
\nZat\u00edmco Thein identifikoval gen v lidsk\u00fdch populac\u00edch, Orkin se zam\u011b\u0159il na d\u016fkaz, \u017ee mohou b\u00fdt manipulov\u00e1ny pro terapeutick\u00e9 \u00fa\u010dely. V roce 2011 jeho t\u00fdm vytvo\u0159il my\u0161i se srpkovitou an\u00e9mi\u00ed a pou\u017eil genetick\u00e9 n\u00e1stroje k deaktivaci genu BCL11A konkr\u00e9tn\u011b v jejich vyv\u00edjej\u00edc\u00edch se \u010derven\u00fdch krvink\u00e1ch. V\u00fdsledek byl ohromuj\u00edc\u00ed: my\u0161i byly zcela opraveny a z\u016fstaly zdrav\u00e9.<\/p>\nNov\u00e1 \u00e9ra l\u00e9\u010dby<\/h3>\n
\n* * * Funk\u010dn\u00ed vyl\u00e9\u010den\u00ed: * * v\u00edce ne\u017e 90% \u00fa\u010dastn\u00edk\u016f testu Vertex prok\u00e1zalo funk\u010dn\u00ed zlep\u0161en\u00ed.
\n* * * \u0158e\u0161en\u00ed p\u0159\u00edznak\u016f: * * * pacienti se srpkovitou an\u00e9mi\u00ed hl\u00e1sili \u00fapln\u00e9 ukon\u010den\u00ed bolestiv\u00fdch kriz\u00ed.
\n* * * Nez\u00e1vislost na transfuz\u00edch: * * * pacienti s beta thalassemi\u00ed ji\u017e nepot\u0159ebovali krevn\u00ed transfuze nebo transplantaci kostn\u00ed d\u0159en\u011b.<\/p>\n\n
Probl\u00e9m dostupnosti<\/h3>\n
\n1. Odb\u011br kmenov\u00fdch bun\u011bk pacienta.
\n2. Jejich \u00fapravy ve specializovan\u00e9 laborato\u0159i.
\n3. Intenzivn\u00ed chemoterapie k \u010di\u0161t\u011bn\u00ed kostn\u00ed d\u0159en\u011b.
\n4. Reinfuze upraven\u00fdch bun\u011bk.<\/p>\nCesta vp\u0159ed: jednodu\u0161\u0161\u00ed zp\u016fsoby l\u00e9\u010dby<\/h3>\n
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\nIdentifikace genu BCL11A p\u0159edstavuje velk\u00fd skok v l\u00e9\u010db\u011b srpkovit\u00e9 an\u00e9mie, p\u0159echod od spr\u00e1vy p\u0159\u00edznak\u016f k funk\u010dn\u00edmu vyl\u00e9\u010den\u00ed. I kdy\u017e jsou sou\u010dasn\u00e9 genov\u00e9 terapie drah\u00e9 a slo\u017eit\u00e9, podporuj\u00ed v\u011bdeckou cestu t\u00edm, \u017ee stimuluj\u00ed nal\u00e9hav\u00fd v\u00fdzkum sm\u011brem k jednodu\u0161\u0161\u00edm a dostupn\u011bj\u0161\u00edm l\u00e9\u010debn\u00fdm metod\u00e1m pro miliony lid\u00ed v nouzi.<\/p>\n","protected":false},"excerpt":{"rendered":"