ozi

Ihe e ji mara hyperlipidemia agwakọta bụ ọkwa plasma dị elu nke lipoproteins dị obere (LDL) na lipoproteins bara ụba nke triglyceride, na-eduga n'ihe ize ndụ dị ukwuu nke ọrịa obi atherosclerotic na ndị ọrịa a.
ANGPTL3 na-egbochi lipoprotein lipase na endosepiase, yana imeju imeju nke lipoproteins bara ụba nke triglyceride. Ndị na-ebu ANGPTL3 adịghị arụ ọrụ dị iche iche nwere ọkwa dị ala nke triglycerides, LDL cholesterol, lipoprotein dị elu (HDL) cholesterol, na cholesterol na-abụghị HDL, yana obere ihe ize ndụ nke ọrịa obi na atherosclerotic. zodasiran bụ obere ọgwụ RNA (RNAi) na-etinye aka na-elekwasị anya okwu ANGPTL3 n'ime imeju.

Ngwakọta hyperlipidemia na-ezo aka na ọkwa dị elu nke lipoprotein cholesterol dị obere (LDL-C) na lipoproteins bara ụba nke triglyceride. Lipoproteins bara ụba nke triglyceride (gụnyere chylomicrons, lipoproteins dị obere (VLDL), na cholesterol fọdụrụnụ) na-ekere òkè dị mkpa na mmepe nke ọrịa atherosclerotic. Enweghị ọgwụgwọ dị mma maka agwakọta hyperlipidemia.
A maara bates ka ọ belata ọkwa triglyceride (TG), mana mbelata ahụ nwere oke. N'otu oge ahụ, ọgwụ na-ebelata TG gụnyere Bates (dị ka eicosapentaenoic acetic acid, wdg) enweghị mmetụta dị ịrịba ama n'ihe ize ndụ nke ọrịa atherosclerotic kpatara site na ọkwa cholesterol fọdụrụnụ dị elu. Na mgbakwunye, ọmụmụ ndị gara aga na ndị ọrịa na-ewerelarị statins egosila na ngwakọta ọgwụ na-ebelata TG anaghị ebelata ohere nke ihe omume obi. Ihe ndị a na-eme ka ọgwụgwọ hyperlipidemia agwakọta sie ike.
ANGPTL3 (angiopoietin-dị ka protein 3) na-achịkwa lipids na lipoprotein metabolism, gụnyere TG na cholesterol lipoprotein na-abụghị nke dị elu (HDL-C), site n'iweghachi azụ na-egbochi lipoprotein lipase, endosepiase, na obere njupụta lipoprotein (LDL) na-anabata hepaprotein. A chọpụtala na ANGPTL3 inactivation variant na-eduga n'ịba ụba lipoprotein lipase na endosepiase ọrụ, nke n'aka nke ya na-eduga n'ọkwa lipoprotein plasma dị ala n'ọtụtụ ọnọdụ, Ndị a gụnyere triglyceride-rich lipoproteins (ie Chylomicrons, cholesterol residual, VLDL, medium density lipoprotein [IDL]), lipoprotein lipoprotein (IDL), lipoprotein (IDL), lipoproteins dị elu). lipoprotein (a), na ihe mejupụtara ya. Ndị heterozygous ndị na-ebu ụdị a nwere ihe dị ka 40% mbelata ohere nke ọrịa atherosclerotic, ọ nweghịkwa phenotype nke ụlọ ọgwụ ahụbeghị. A na-egosipụta ANGPTL3 n'ime imeju, yana usoro ọgwụgwọ na-emechi mkpụrụ ndụ ihe nketa na-elekwasị anya mRNA ya, nke a maara dị ka obere ọgwụ RNA (siRNA) na-etinye aka, bụ ọgwụgwọ ngwakọ na-ekwe nkwa maka hyperlipidemia.
Na Septemba 12, 2024, akwụkwọ akụkọ New England Journal of Medicine (NEJM) bipụtara ọmụmụ ARCHES 2 na-akwado na zodasiran ọgwụ siRNA belatara ọkwa TG nke ukwuu na ndị ọrịa nwere hyperlipidemia agwakọta [1]. ARCHES-2 bụ kpuru ìsì okpukpu abụọ, nke a na-achịkwa placebo, usoro nyocha nke usoro 2b. Ngụkọta ndị ọrịa 204 nwere hyperlipidemia agwakọta (ọkwa TG na-ebu ọnụ 150-499 mg/dL, ọkwa LDL-C ³70 mg/dL ma ọ bụ ọkwa HDL-C ³100 mg/dL) debara aha. E kewara ha n'ime zodasiran 50 mg, otu 100 mg, otu 200 mg na otu njikwa placebo. Ndị ọrịa na-anata injections subcutaneous na izu 1 na 12, ma nata usoro prophylaxis ruo izu 36.
Isi njedebe bụ mgbanwe pasentị na TG site na ntọala ruo izu 24. Nnyocha ahụ chọpụtara na site na izu 24, ọkwa TG na òtù zodasiran na-ebelata nke ukwuu n'ụzọ dabere na dose (TG na ọkwa nke ọ bụla na-ebelata site na 51, 57 na 63 pasent, n'otu n'otu, ma e jiri ya tụnyere ndị nọ na placebo otu) (P <0.001). ANGPTL3 gbadakwara site na pasent 54, isi pasenti 70 na pasentị 74, n'otu n'otu. Ọkwa ndị na-abụghị HDl-c belatara site na pasent 29, pasent 29, na pasent 36, ọkwa apolipoprotein B belatara site na pasent 19, pasent 15, na pasent 22, na ọkwa LDL-C belatara site na pasent 16, pasent 14, na pasent 20 na-adịgide adịgide ruo n'izu ndị a. N'ime izu 24, zodasiran
N'ime 88% nke ndị ọrịa nọ na otu 200 mg, TG na-ebu ọnụ adaala n'ụdị nkịtị.

Àkụ na-acha uhie uhie na ụbọchị 1 na 12 na-egosi nchịkwa zodasiran ma ọ bụ placebo.

Ọkwa TG na-ebu ọnụ belatara ka ọ dị na izu 24 (150
mg/dL ma ọ bụ obere)
Ogidi ọ bụla na-anọchi anya otu onye ọrịa.

Ọmụmụ ihe ahụ chọpụtakwara na zotasiran dị nchebe na otu ọgwụ niile, ebe naanị ndị ọrịa 2 kwụsịrị ọmụmụ ihe n'ihi ihe ọjọọ (1 na placebo otu na 1 na 100 mg zotasiran Group). Ihe omume ọjọọ niile dị na otu zotasiran gbakere na njedebe nke ọmụmụ ahụ, ma enwere otu ọnwụ na otu placebo. Naanị ihe omume ọjọọ nke nchegbu bụ mmụba na HBA1c na 200 mg zotasiran otu ma e jiri ya tụnyere placebo ( pụtara mgbanwe site na ntọala ruo izu 24 [± SD], 0.38 ± 0.66% vs. -0.03± 0.88% na ndị ọrịa nwere ọrịa shuga na-adịbu). Ndị ọrịa na-enweghị ọrịa shuga bụ 0.12± 0.19% vs. -0.03±0.19%).
Karịsịa, ihe fọrọ nke nta ka ọ bụrụ ndị ọrịa niile nọ n'ọmụmụ ihe (96%) ka a na-eji statins (37% nke bụ statins dị elu), 1% na-eji proprotein na-agbanwe enzyme subtilysin 9 inhibitor (PCSK9i), na 21% na-eji fibrates agwọ ya. Ya mere, mgbakwunye nke zodasiran na ndabere nke usoro ọgwụgwọ a na-eme ugbu a ka na-enweta mmetụta dị ala nke lipid, nke na-enye usoro ọhụrụ maka ọgwụgwọ hyperlipidemia agwakọta n'ọdịnihu.
N'izu 24, oke dose nke 200 mg nke zotasiran n'ime ọmụmụ ahụ belatara ọkwa cholesterol fọdụrụnụ site na 34.4 mg/dL ma e jiri ya tụnyere placebo. Dabere na ụdị dị ugbu a, a na-atụ anya na mbelata a ga-ebelata ihe omume obi mgbawa site na pasent 20. zodasiran nwere ike iji dị ka monotherapy maka ihe niile lipoprotein mejupụtara iji belata ihe ize ndụ nke ihe omume obi na ndị ọrịa. Ya mere, nyocha ọzọ dị mkpa iji chọpụta ike ọgwụ a nwere n'ibelata ihe ize ndụ nke ọrịa atherosclerotic.
Usoro 2b, nke kpuru ìsì abụọ, nke enweghị usoro, ọmụmụ MUIR na-achịkwa placebo, nke e bipụtara n'otu oge na NEJM, jiri ọgwụ siRNA ọzọ, plozasiran, na-agwọ hyperlipidemia agwakọta [2]. Emebere plozasiran iji belata okwu APOC3, mkpụrụ ndụ ihe nketa apolipoprotein C3 (APOC3), onye na-achịkwa metabolism TG, n'ime imeju, si otú ahụ belata TG na ọkwa cholesterol fọdụrụnụ. Mbelata nke TG na ọkwa kọlestrọl fọdụrụnụ a hụrụ na ọmụmụ ihe ahụ yiri nke a hụrụ na ọmụmụ ARCHES-2. Ya mere, a na-eche na n'ime ndị ọrịa nwere hyperlipidemia agwakọta, ọgwụ abụọ ahụ nwere mmetụta yiri nke ahụ n'ibelata ọkwa nke lipoprotein bara ụba nke triglyceride na cholesterol fọdụrụnụ.
Nsonaazụ nke ọmụmụ siRNA abụọ gosiri na nke a bụ ọgwụ na-ekwe nkwa nke ukwuu nke ga-eweta nhọrọ ọhụrụ maka ọgwụgwọ hyperlipidemia agwakọta ma melite nsonaazụ obi na ndị ọrịa.