Od Gregora Mendela, kter\u00fd je pova\u017eov\u00e1n za otce genetiky, po Watson a Crick, objevitele \u00a0struktury DNA dvou\u0161roubovice, uplynulo u\u017e mnoho let a ka\u017ed\u00fdm dnem p\u0159ib\u00fdvaj\u00ed v\u00a0medic\u00edn\u011b dal\u0161\u00ed objevy t\u00fdkaj\u00edc\u00ed se vztah\u016f mezi na\u0161\u00ed genetickou informac\u00ed a nemocemi. Na\u0161e geny tak\u00e9 velmi pravd\u011bpodobn\u011b ovliv\u0148uj\u00ed do ur\u010dit\u00e9 m\u00edry \u010d\u00edm jsme a proto m\u016f\u017eeme s\u00a0ur\u010ditou pravd\u011bpodobnost\u00ed \u0159\u00edci, \u017ee v\u011bt\u0161ina nemoc\u00ed ne-li v\u0161echny jsou zak\u00f3dovan\u00e9 v\u00a0na\u0161\u00ed DNA.<\/p>\n
P\u0159\u00edkladem mohou b\u00fdt nemoci, jako jsou obezita, hypertenze, diabetes mellitus. Tato onemocn\u011bn\u00ed zahrnuj\u00ed interakce mezi mnoha r\u016fzn\u00fdmi geny a tak\u00e9 prost\u0159ed\u00edm v\u00a0jak\u00e9m se nach\u00e1z\u00edme. V\u00edme v\u0161ak, \u017ee existuj\u00ed i takov\u00e9 nemoci, jako je cystick\u00e1 fibr\u00f3za, talasemie, n\u011bkter\u00e9 formy leuk\u00e9mie, kter\u00e9 jsou zp\u016fsobeny prim\u00e1rn\u011b specifickou mutac\u00ed nebo zm\u011bnou v DNA.<\/p>\n
Teorie je tedy takov\u00e1, \u017ee pokud dok\u00e1\u017eeme opravit \u0161patnou DNA, budeme schopni takto nemocn\u00e9 lidi vyl\u00e9\u010dit. Tato teorie se v\u0161ak ji\u017e stala prax\u00ed, jeliko\u017e genov\u00e1 terapie je ji\u017e na trhu a vyu\u017e\u00edv\u00e1 se pro l\u00e9\u010dbu vybran\u00fdch nemoc\u00ed. Prim\u00e1rn\u011b nemoc\u00ed, kter\u00e9 jsou zp\u016fsobeny vadou jednoho genu \u2013 monogenn\u00ed choroby. Genov\u00e1 terapie se tedy vyu\u017e\u00edv\u00e1 nap\u0159\u00edklad na l\u00e9\u010dbu Leberovi vrozen\u00e9 slepoty \u010di LCA.<\/p>\n
LCA je genetick\u00fd stav, kter\u00fd postihuje hlavn\u011b s\u00edtnici oka. Jednotlivci s t\u00edmto stavem obvykle trp\u00ed progresivn\u00edm zrakov\u00fdm probl\u00e9mem na po\u010d\u00e1tku \u017eivota a pozd\u011bji u nich dokonce hroz\u00ed i slepota. Toto onemocn\u011bn\u00ed je zp\u016fsobeno genetick\u00fdmi defekty, kter\u00e9 jsou v sou\u010dasn\u00e9 dob\u011b p\u0159ipisov\u00e1ny v\u00edce ne\u017e 19 r\u016fzn\u00fdm gen\u016f – \u00a0GUCY2D, RPE65, SPATA7, AIPL1 atd. L\u00e9\u010dba LCA byla bohu\u017eel a\u017e doned\u00e1vna podp\u016frn\u00e1. Koncem prosince 2017 byla v\u0161ak schv\u00e1lena za souhlasu FDA (Food and Drug Administration) nov\u00e1 genov\u00e1 terapie. L\u00e9k se prod\u00e1v\u00e1 pod n\u00e1zvem Luxturna (voretigene neparvovec) a je vyvinut\u00fd spole\u010dnost\u00ed Spark Therapeutics. Funguje tak, \u017ee poskytuje funk\u010dn\u00ed kopii genu RPE65 u jedinc\u016f s LCA typem II pomoc\u00ed deaktivovan\u00e9ho adeno-asociovan\u00e9ho viru (AAV).<\/p>\n
Toto rozhodnut\u00ed FDA bylo zalo\u017eeno na v\u00fdsledku randomizovan\u00e9 kontrolovan\u00e9 klinick\u00e9 studie ve f\u00e1zi III, kter\u00e1 byla provedena Russell a jeho kolegy v roce 2017, p\u0159i\u010dem\u017e v\u00fdsledek jejich studie uk\u00e1zal v\u00fdznamn\u00fd rozd\u00edl a zlep\u0161en\u00ed stavu pacienta, kter\u00fd dost\u00e1val ji\u017e zm\u00edn\u011bn\u00fd l\u00e9k, ve srovn\u00e1n\u00ed s kontroln\u00ed skupinou. Hl\u00e1sili pouze m\u00edrn\u00e9 a\u017e st\u0159edn\u00ed ne\u017e\u00e1douc\u00ed \u00fa\u010dinky, jako je zv\u00fd\u0161en\u00fd nitroo\u010dn\u00ed tlak, m\u00edrn\u00fd \u0161ed\u00fd z\u00e1kal, m\u00edrn\u00e9 trhliny v s\u00edtnici atd., kter\u00e9 ve v\u011bt\u0161in\u011b p\u0159\u00edpad\u016f ustoupily samostatn\u011b nebo s intervenc\u00ed.<\/p>\n
Spolu s p\u0159\u00edpravkem Luxturna jsou na trhu k dispozici l\u00e9ky zvan\u00e9 Kymriah, pro l\u00e9\u010dbu akutn\u00ed lymfoblastick\u00e9 leuk\u00e9mie a Yescarta, pro l\u00e9\u010dbu non-Hodgkinova lymfomu (NHL). Kymriah a Yescarta pracuj\u00ed trochu jinak ne\u017e Luxturna. Hlavn\u00ed rozd\u00edl mezi nimi spo\u010d\u00edv\u00e1 v tom, \u017ee Luxturna zahrnuje genovou modifikaci virem uvnit\u0159 lidsk\u00e9ho t\u011bla technikou zn\u00e1mou jako genov\u00e1 terapie in vivo. Na druh\u00e9 stran\u011b Kymriah a Yescarta zahrnuj\u00ed odeb\u00edr\u00e1n\u00ed b\u00edl\u00fdch krvinek od pacienta pomoc\u00ed leukafer\u00e9zy, n\u00e1slednou modifikaci t\u011bchto bun\u011bk v laborato\u0159i a jejich op\u011btovn\u00e9 zaveden\u00ed zp\u011bt do t\u011bla pacienta. Pro tento typ l\u00e9\u010dby se tedy pou\u017e\u00edv\u00e1 n\u00e1zev ex-vivo genov\u00e1 terapie.<\/p>\n
Zat\u00edmco Luxturna je prvn\u00ed schv\u00e1lenou in vivo genovou terapi\u00ed, Strimvelis je prvn\u00ed schv\u00e1lenou ex vivo genovou terapi\u00ed, kter\u00e1 se pou\u017e\u00edv\u00e1 k l\u00e9\u010db\u011b deficitu adenosinov\u00e9 deamin\u00e1zy (ADA). ADA vede ke stavu zvan\u00e9mu t\u011b\u017ek\u00e1 kombinovan\u00e1 imunodeficience (SCID) nebo l\u00e9pe zn\u00e1m\u00e9mu jako syndrom chlapce v bublin\u011b, proto\u017ee jedinci s t\u00edmto onemocn\u011bn\u00edm maj\u00ed slab\u00fd imunitn\u00ed syst\u00e9m a doch\u00e1z\u00ed k\u00a0mnohem jednodu\u0161\u0161\u00edmu naka\u017een\u00ed se mikroorganismy.<\/p>\n
Genov\u00e1 terapie je tedy dostupn\u00e1 pouze u vz\u00e1cn\u00fdch onemocn\u011bn\u00ed a bohu\u017eel je velmi finan\u010dn\u011b n\u00e1kladn\u00fd. Rychl\u00e9 vyhled\u00e1v\u00e1n\u00ed na internetu ukazuje, \u017ee Luxturna stoj\u00ed p\u0159ibli\u017en\u011b 746 000 $ na pacienta, Kymriah 305 800 $, \u00a0Yescarta 373 000 $ a Strimvelis 714 000 $. To vyvol\u00e1v\u00e1 etickou ot\u00e1zku, kdo si m\u016f\u017ee tyto l\u00e9ky dovolit. Existuj\u00ed tak\u00e9 i dal\u0161\u00ed ot\u00e1zky nap\u0159\u00edklad, jak dob\u0159e budou tyto l\u00e9ky fungovat v\u00a0dlouhodob\u00e9m m\u011b\u0159\u00edtku, zda existuj\u00ed i jin\u00e9 nezaznamenan\u00e9 vedlej\u0161\u00ed \u00fa\u010dinky, nebo zda poji\u0161\u0165ovna bude ochotna za tyto drah\u00e9 l\u00e9\u010dby platit. M\u016f\u017eeme v\u0161ak s\u00a0jistotou \u0159\u00edci, \u017ee tento pokrok v genov\u00e9 terapii n\u00e1m poskytuje pevn\u00fd z\u00e1klad pro v\u00fdvoj budouc\u00ed l\u00e9\u010dby pro dal\u0161\u00ed typy onemocn\u011bn\u00ed.<\/p>\n
<\/p>\n
Zdroj:<\/p>\n
Russell, S., Bennett, J., Wellman, J. A., Chung, D. C., Yu, Z. F., Tillman, A., et al. (2017). Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet (London, England), 390(10097), 849\u2013860. doi:10.1016\/S0140-6736(17)31868-8<\/p>\n
Weleber RG, Francis PJ, Trzupek KM, et al. Leber Congenital Amaurosis. 2004 Jul 7 [Updated 2013 May 2]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1298\/<\/p>\n
Clarke, T., & Berkrot, B. (2017, October 19). FDA approves Gilead cancer gene therapy; price set at $373,000. Reuters. Retrieved from https:\/\/www.reuters.com\/article\/us-gilead-sciences-fda\/fda-approves-gilead-cancer-gene-therapy-price-set-at-373000-idUSKBN1CN35H<\/p>\n
Pagliarulo, N. (2019, September 4). Novartis secures NICE nod for Luxturna with discount offer . Biopharmadrive. Retrieved from https:\/\/www.biopharmadive.com\/news\/nice-luxturna-gene-therapy-recommendation-novartis-discount\/562211\/<\/p>\n
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