Kev sib xyaw hyperlipidemia yog tus cwj pwm los ntawm kev nce qib ntawm cov ntshav lipoproteins tsawg (LDL) thiab triglyceride-nplua nuj lipoproteins, uas ua rau muaj kev pheej hmoo ntawm atherosclerotic cardiovascular kab mob hauv cov neeg mob no.
ANGPTL3 inhibits lipoprotein lipase thiab endosepiase, nrog rau lub siab nce ntawm triglyceride-nplua nuj lipoproteins. Cov neeg nqa khoom ntawm ANGPTL3 inactivated variant muaj qis qis ntawm triglycerides, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, thiab tsis-HDL cholesterol, nrog rau kev pheej hmoo ntawm atherosclerotic cardiovascular kab mob. zodasiran yog ib qho tshuaj me me cuam tshuam RNA (RNAi) uas tsom rau ANGPTL3 qhia hauv daim siab.
Kev sib xyaw hyperlipidemia yog hais txog qib siab ntawm cov lipoprotein tsawg-density lipoprotein (LDL-C) thiab triglyceride-nplua nuj lipoproteins. Triglyceride-nplua nuj lipoproteins (xws li chylomicrons, tsawg ntom lipoproteins (VLDL), thiab cov roj cholesterol seem) ua lub luag haujlwm tseem ceeb hauv kev txhim kho cov kab mob atherosclerotic. Tsis muaj kev kho mob zoo rau kev sib xyaw hyperlipidemia.
Bates paub tias txo cov qib triglyceride (TG), tab sis qhov txo qis. Nyob rau tib lub sijhawm, TG txo cov tshuaj suav nrog Bates (xws li eicosapentaenoic acetic acid, thiab lwm yam) tsis muaj txiaj ntsig zoo rau kev pheej hmoo ntawm atherosclerotic kab mob tshwm sim los ntawm cov qib roj cholesterol siab. Tsis tas li ntawd, cov kev tshawb fawb yav dhau los hauv cov neeg mob twb tau noj statins tau pom tias kev sib xyaw ua ke ntawm TG-txo cov tshuaj tsis txo qhov kev pheej hmoo ntawm cov kab mob plawv. Cov xwm txheej no ua rau kev kho mob sib xyaw hyperlipidemia nyuaj heev.
ANGPTL3 (angiopoietin-zoo li protein 3) tswj cov lipids thiab lipoprotein metabolism, suav nrog TG thiab tsis-high-density lipoprotein cholesterol (HDL-C), los ntawm reversibly inhibiting lipoprotein lipase, endosepiase, thiab low-density lipoprotein (LDL) receptor-dependent. Nws tau pom tias ANGPTL3 inactivation variant ua rau nce lipoprotein lipase thiab endosepiase kev ua haujlwm, uas ua rau cov ntshav plasma lipoprotein qis hauv feem ntau, Cov no suav nrog triglyceride-nplua nuj lipoproteins (piv txwv li Chylomicrons, residual cholesterol, VLDL, nruab nrab LID-density, lipoprotein density) lipoprotein (HDL), lipoprotein (a), thiab lawv cov roj cholesterol. Cov neeg heterozygous uas muaj qhov sib txawv no muaj kwv yees li 40% txo qhov kev pheej hmoo ntawm cov kab mob atherosclerotic, thiab tsis pom muaj cov tsos mob tsis zoo. ANGPTL3 tau qhia nyob rau hauv daim siab, thiab gene silencing therapies tsom nws mRNA, hu ua me me interfering RNA (siRNA) tshuaj, yog ib tug cog lus hybrid kev kho mob rau hyperlipidemia.
Thaum lub Cuaj Hlis 12, 2024, New England Journal of Medicine (NEJM) tau luam tawm ARCHES 2 txoj kev tshawb fawb pom tseeb tias cov tshuaj siRNA zodasiran txo qis TG qib hauv cov neeg mob uas muaj kev sib xyaw hyperlipidemia [1]. ARCHES-2 yog ob qhov muag tsis pom kev, cov tshuaj placebo-tswj, koob tshuaj ntau qhov kev tshawb nrhiav theem 2b sim. Tag nrho ntawm 204 tus neeg mob uas muaj kev sib xyaw hyperlipidemia (kev yoo mov TG qib 150-499 mg / dL, LDL-C qib ³70 mg / dL lossis tsis yog HDL-C qib ³100 mg / dL) tau cuv npe. Lawv tau muab faib ua zodasiran 50 mg pawg, 100 mg pawg, 200 mg pawg thiab cov placebo tswj pawg. Cov neeg mob tau txais kev txhaj tshuaj subcutaneous ntawm lub lim tiam 1 thiab 12, thiab tau txais kev tiv thaiv kev tiv thaiv mus txog rau lub lim tiam 36.
Thawj qhov kawg yog qhov feem pua ntawm kev hloov pauv hauv TG los ntawm lub hauv paus rau lub lim tiam 24. Txoj kev tshawb fawb pom tias los ntawm lub lim tiam 24, TG qib hauv pawg zodasiran tau txo qis hauv txoj kev siv tshuaj ntau npaum li cas (TG qib hauv txhua pawg koob tshuaj tau txo los ntawm 51, 57 thiab 63 feem pua ntawm cov ntsiab lus, feem, piv nrog rau cov nyob hauv pawg placebo.0sari) (P. ANGPTL3 kuj tau txo los ntawm 54 feem pua ntawm cov ntsiab lus, 70 feem pua cov ntsiab lus thiab 74 feem pua cov ntsiab lus, feem. Tsis yog-hdl-c qib tau txo qis los ntawm 29 feem pua ntawm cov ntsiab lus, 29 feem pua cov ntsiab lus, thiab 36 feem pua cov ntsiab lus, apolipoprotein B qib txo qis los ntawm 19 feem pua ntawm cov ntsiab lus, 15 feem pua cov ntsiab lus, thiab 22 feem pua cov ntsiab lus, thiab LDL-C qib tau txo qis los ntawm 16 feem pua cov ntsiab lus, 14 feem pua ntawm cov ntsiab lus, thiab 20 feem pua ntawm cov ntsiab lus ntawm lub lim tiam. Hauv lub lim tiam 24, zodasiran
Hauv 88% ntawm cov neeg mob hauv pawg 200 mg, kev yoo mov TG tau poob mus rau qhov qub.
Cov xub liab nyob rau hnub 1 thiab 12 qhia zodasiran lossis placebo tswj hwm.
Kev yoo mov TG qib txo qis rau ib txwm nyob rau lub lim tiam 24 (150
mg/dL los yog tsawg dua)
Txhua tus ncej sawv cev rau ib tus neeg mob.
Txoj kev tshawb no kuj pom tias zotasiran muaj kev nyab xeeb nyob rau hauv txhua pawg koob tshuaj, tsuas yog 2 tus neeg mob txiav kev kawm vim muaj cov xwm txheej tsis zoo (1 hauv pawg placebo thiab 1 hauv 100 mg zotasiran pawg). Tag nrho cov xwm txheej tsis zoo hauv pawg zotasiran rov qab los ntawm qhov kawg ntawm txoj kev tshawb no, thiab muaj ib tus neeg tuag hauv cov placebo. Qhov tsuas yog qhov tshwm sim tsis zoo ntawm kev txhawj xeeb yog qhov nce hauv HBA1c hauv 200 mg zotasiran pawg piv nrog cov placebo (txhais tau tias hloov pauv ntawm lub hauv paus mus rau lub lim tiam 24 [±SD], 0.38±0.66% vs. -0.03±0.88% hauv cov neeg mob ntshav qab zib preexisting). Cov neeg mob uas tsis muaj ntshav qab zib yog 0.12 ± 0.19% vs. -0.03 ± 0.19%).
Tshwj xeeb, yuav luag txhua tus neeg mob hauv txoj kev tshawb no (96%) tau kho nrog statins (37% ntawm cov tshuaj statins), 1% tau kho nrog cov protein hloov pauv enzyme subtilysin 9 inhibitor (PCSK9i), thiab 21% tau kho nrog fibrates. Yog li ntawd, qhov sib ntxiv ntawm zodasiran nyob rau hauv lub hauv paus ntawm txoj kev kho mob niaj hnub no tseem ua tiav cov txiaj ntsig lipid-txo qis, uas muab cov kev tswj hwm tshiab rau kev kho mob sib xyaw hyperlipidemia yav tom ntej.
Thaum lub lis piam 24, qhov siab tshaj plaws koob tshuaj 200 mg ntawm zotasiran hauv txoj kev tshawb no txo qis cov roj cholesterol seem los ntawm 34.4 mg / dL piv rau cov placebo. Raws li cov qauv tam sim no, qhov kev txo qis no yuav tsum txo qis kev mob plawv loj los ntawm 20 feem pua. zodasiran muaj peev xwm siv tau los ua ib qho kev kho mob monotherapy rau tag nrho cov lipoprotein Cheebtsam los txo cov kev pheej hmoo ntawm cov hlab plawv hauv cov neeg mob. Yog li ntawd, kev tshawb fawb ntxiv yog qhov tsim nyog los txiav txim siab lub peev xwm ntawm cov tshuaj no hauv kev txo qis kev pheej hmoo ntawm atherosclerotic kab mob.
Theem 2b, ob-dig muag, randomized, placebo-tswj MUIR txoj kev tshawb fawb, luam tawm ib txhij hauv NEJM, siv lwm cov tshuaj siRNA, plozasiran, los kho cov ntshav siab sib xyaw [2]. plozasiran yog tsim los txo cov kev qhia ntawm APOC3, cov noob encoding apolipoprotein C3 (APOC3), ib tug regulator ntawm TG metabolism, nyob rau hauv daim siab, yog li txo TG thiab residual cholesterol. Qhov txo qis hauv TG thiab cov roj cholesterol seem hauv txoj kev tshawb fawb tau zoo ib yam li cov uas pom hauv ARCHES-2 txoj kev tshawb fawb. Yog li, nws tau kwv yees tias nyob rau hauv cov neeg mob uas muaj kev sib xyaw hyperlipidemia, ob cov tshuaj muaj cov txiaj ntsig zoo sib xws hauv kev txo qis qib ntawm triglyceride-nplua nuj lipoprotein thiab cov cholesterol seem.
Cov txiaj ntsig ntawm ob txoj kev tshawb fawb siRNA qhia tau hais tias qhov no yog ib chav kawm zoo heev ntawm cov tshuaj uas yuav coj cov kev xaiv tshiab rau kev kho mob sib xyaw hyperlipidemia thiab txhim kho cov txiaj ntsig ntawm cov hlab plawv hauv cov neeg mob.
Post lub sij hawm: Sep-15-2024