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Haɗaɗɗen hyperlipidemia yana haɓaka da haɓaka matakan plasma na ƙananan lipoproteins masu ƙarancin yawa (LDL) da lipoproteins masu wadatar triglyceride, wanda ke haifar da haɗarin cututtukan cututtukan zuciya na atherosclerotic a cikin wannan yawan masu haƙuri.
ANGPTL3 yana hana lipoprotein lipase da endosepiase, da kuma ɗaukar hanta na lipoproteins mai arzikin triglyceride. Masu ɗaukar nau'in bambance-bambancen da ba a kunna ba na ANGPTL3 suna da ƙananan matakan triglycerides, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, da waɗanda ba HDL cholesterol, kazalika da ƙananan haɗarin cututtukan atherosclerotic na zuciya da jijiyoyin jini. zodasiran ƙaramin maganin RNA (RNAi) ne mai shiga tsakani wanda ke hari ANGPTL3 magana a cikin hanta.

Mixed hyperlipidemia yana nufin haɓakar matakan ƙananan ƙarancin lipoprotein cholesterol (LDL-C) da lipoproteins mai arzikin triglyceride. Lipoproteins masu wadatar triglyceride (ciki har da chylomicrons, ƙananan lipoproteins masu ƙarancin yawa (VLDL), da ragowar cholesterol) suna taka muhimmiyar rawa wajen haɓaka cututtukan atherosclerotic. Babu ingantaccen magani ga gauraye hyperlipidemia.
An san bates don rage matakan triglyceride (TG), amma raguwa yana da iyaka. A lokaci guda, TG rage magunguna ciki har da Bates (kamar eicosapentaenoic acetic acid, da dai sauransu) ba su da wani tasiri mai mahimmanci akan haɗarin cututtukan atherosclerotic wanda ya haifar da haɓakar matakan cholesterol mai girma. Bugu da ƙari, binciken da aka yi a baya a cikin marasa lafiya da suka riga sun dauki statins sun nuna cewa haɗuwa da kwayoyi masu rage TG ba su rage hadarin cututtukan zuciya ba. Wadannan abubuwan suna sa maganin hyperlipidemia gauraye da wahala sosai.
ANGPTL3 (angiopoietin-kamar furotin 3) yana sarrafa lipids da lipoprotein metabolism, gami da TG da cholesterol mara nauyi mai yawa (HDL-C), ta hanyar sake hana lipoprotein lipase, endosepiase, da ƙananan ƙarancin lipoprotein (LDL) mai karɓa. An gano cewa bambance-bambancen rashin kunnawa na ANGPTL3 yana haifar da haɓakar lipoprotein lipase da ayyukan endosepiase, wanda hakan ke haifar da ƙarancin matakan lipoprotein na plasma a mafi yawan lokuta, Waɗannan sun haɗa da lipoproteins masu wadatar triglyceride (watau Chylomicrons, ragowar cholesterol, VLDL, matsakaicin yawa lipoprotein [HDL), lipoprotein [HDL]), LDL, LDL, HDD, LDL, LDL, LDL, LDL, LTD, LDL, LTD, LDL, LDS, LTD, LDL, LDL, Lipoproteins, Lipoproteins, da VLDL. lipoprotein (a), da abubuwan da ke tattare da cholesterol. Mutanen Heterozygous waɗanda ke ɗauke da wannan bambance-bambancen suna da kusan 40% rage haɗarin cututtukan atherosclerotic, kuma ba a sami wani mummunan yanayin na asibiti ba. ANGPTL3 an bayyana shi a cikin hanta, da kuma hanyoyin kwantar da kwayar halitta da ke niyya ga mRNA, wanda aka sani da ƙananan magungunan RNA (siRNA) masu shiga tsakani, wani kyakkyawan magani ne na hyperlipidemia.
A ranar 12 ga Satumba, 2024, Jaridar New England Journal of Medicine (NEJM) ta buga wani binciken ARCHES 2 yana mai tabbatar da cewa siRNA miyagun ƙwayoyi zodasiran ya rage matakan TG sosai a cikin marasa lafiya tare da gauraye hyperlipidemia [1]. ARCHES-2 makafi biyu ne, mai sarrafa wuribo, gwaji na lokaci-lokaci 2b. Jimlar marasa lafiya 204 tare da gauraye hyperlipidemia (matakin TG masu azumi 150-499 mg/dL, matakan LDL-C ³70 mg/dL ko matakan HDL-C ³100 mg/dL) sun yi rajista. An raba su zuwa ƙungiyar zodasiran 50 MG, ƙungiyar 100 MG, ƙungiyar 200 MG da ƙungiyar kula da placebo. Marasa lafiya sun sami alluran subcutaneous a mako na 1 da 12, kuma sun sami rigakafin rigakafin har zuwa mako na 36.
Mahimmin mahimmanci shine canjin kashi a cikin TG daga asali zuwa mako na 24. Binciken ya gano cewa a cikin mako na 24, matakan TG a cikin ƙungiyar zodasiran sun ragu sosai a cikin hanyar da ta dogara da kashi (TG matakan a cikin kowane kashi kashi an rage ta 51, 57 da 63 kashi kashi, bi da bi, idan aka kwatanta da wadanda ke cikin rukunin placebo) (P <0.001) . ANGPTL3 kuma ya ragu da kashi 54 cikin dari, kashi 70 da maki 74, bi da bi. Matakan da ba hdl-c sun ragu da kashi 29 cikin dari, maki 29 da maki 36, matakan apolipoprotein B sun ragu da maki 19, maki 15, da maki 22, kuma matakan LDL-C sun ragu da maki 16, 14 kashi dari, da maki 20 masu daraja, sakamakon mako 3. A mako na 24, zodasiran
A cikin 88% na marasa lafiya a cikin rukunin 200 MG, TG mai azumi ya faɗi zuwa kewayon al'ada.

Jajayen kibau a ranakun 1 da 12 suna nuna zodasiran ko gudanarwar placebo.

Matakan TG masu azumi sun ragu zuwa al'ada a mako na 24 (150
mg/dL ko ƙasa da haka)
Kowane ginshiƙi yana wakiltar majiyyaci ɗaya.

Har ila yau, binciken ya lura cewa zotasiran yana da lafiya a cikin dukkanin nau'o'in nau'i, tare da marasa lafiya 2 kawai sun dakatar da binciken saboda abubuwan da suka faru (1 a cikin rukunin placebo da 1 a cikin 100 MG zotasiran kungiyar). Dukkan abubuwan da suka faru masu tsanani a cikin ƙungiyar zotasiran sun dawo da su a ƙarshen binciken, kuma akwai mutuwar daya a cikin rukunin placebo. Abinda kawai ya faru na damuwa shine karuwa a cikin HBA1c a cikin 200 mg zotasiran kungiyar idan aka kwatanta da placebo (ma'anar canji daga asali zuwa mako 24 [± SD], 0.38 ± 0.66% vs. -0.03 ± 0.88% a cikin marasa lafiya da ciwon sukari na farko). Marasa lafiya marasa ciwon sukari sun kasance 0.12 ± 0.19% vs. -0.03± 0.19%).
Musamman, kusan dukkanin marasa lafiya a cikin binciken (96%) ana bi da su tare da statins (37% daga cikinsu sune statins masu girma), 1% ana bi da su tare da proprotein-converting enzyme subtilysin 9 inhibitor (PCSK9i), kuma 21% ana bi da su tare da fibrates. Sabili da haka, ƙari na zodasiran bisa tsarin tsarin kulawa na yau da kullum har yanzu ya sami sakamako mai yawa na rage yawan lipid, wanda ke ba da sabon tsari don maganin hyperlipidemia gauraye a nan gaba.
A mako na 24, matsakaicin kashi na 200 MG na zotasiran a cikin binciken ya rage yawan ƙwayar cholesterol ta 34.4 mg / dL idan aka kwatanta da placebo. Dangane da nau'ikan na yanzu, ana sa ran wannan raguwar zai rage manyan cututtukan zuciya da kashi 20 cikin ɗari. zodasiran yana da damar da za a yi amfani da shi azaman monotherapy don duk abubuwan haɗin lipoprotein don rage haɗarin cututtukan zuciya da jijiyoyin jini a cikin marasa lafiya. Don haka ƙarin bincike ya zama dole don sanin yuwuwar wannan magani don rage haɗarin cututtukan atherosclerotic.
Mataki na 2b, makafi biyu, bazuwar, nazarin MUIR mai sarrafa wuribo, wanda aka buga lokaci guda a cikin NEJM, ya yi amfani da wani sirna magani, plozasiran, don magance gauraye hyperlipidemia [2]. An tsara plozasiran don rage maganganun APOC3, kwayar halittar apolipoprotein C3 (APOC3), mai kula da metabolism na TG, a cikin hanta, don haka rage TG da sauran matakan cholesterol. Ragewar TG da sauran matakan cholesterol da aka lura a cikin binciken sun kasance daidai da waɗanda aka samu a cikin binciken ARCHES-2. Don haka, ana hasashen cewa a cikin marasa lafiya tare da gauraye hyperlipidemia, magungunan biyu suna da tasiri iri ɗaya wajen rage matakin lipoprotein mai arzikin triglyceride da sauran cholesterol.
Sakamakon binciken biyu na siRNA ya nuna cewa wannan wani nau'i ne mai ban sha'awa na magunguna wanda zai kawo sababbin zaɓuɓɓuka don maganin hyperlipidemia gauraye da inganta sakamakon cututtukan zuciya a cikin marasa lafiya.