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Hōʻike ʻia ka hyperlipidemia i hui ʻia e ka piʻi ʻana o ka pae plasma o nā lipoproteins haʻahaʻa haʻahaʻa (LDL) a me nā lipoproteins waiwai triglyceride, e alakaʻi ana i ka piʻi nui o ka maʻi cardiovascular atherosclerotic i kēia heluna maʻi.
Kāohi ʻo ANGPTL3 i ka lipoprotein lipase a me ka endosepiase, a me ka lawe ʻana o ka ate i nā lipoproteins waiwai triglyceride. ʻO nā mea lawe o ka ANGPTL3 i hoʻohana ʻole ʻia he mau pae haʻahaʻa o ka triglycerides, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, a me ka cholesterol non-HDL, a me ka haʻahaʻa haʻahaʻa o ka maʻi cardiovascular atherosclerotic. ʻO ka zodasiran kahi lāʻau RNA (RNAi) hoʻopilikia liʻiliʻi e kuhikuhi ana i ka ʻōlelo ANGPTL3 i loko o ke ake.

ʻO ka hyperlipidemia hui ʻia e pili ana i nā pae kiʻekiʻe o ka lipoprotein cholesterol haʻahaʻa haʻahaʻa (LDL-C) a me nā lipoproteins waiwai nui i ka triglyceride. ʻO nā lipoproteins waiwai nui o Triglyceride (me nā chylomicrons, very low density lipoproteins (VLDL), a me ke koena cholesterol) ke kuleana nui i ka ulu ʻana o ka maʻi atherosclerotic. ʻAʻohe lāʻau lapaʻau kūpono no ka hyperlipidemia hui ʻia.
Ua ʻike ʻia nā Bates e hoʻemi i nā pae triglyceride (TG), akā ua kaupalena ʻia ka hōʻemi. I ka manawa like, ʻaʻohe hopena koʻikoʻi i ka hopena o ka maʻi atherosclerotic i hoʻokumu ʻia e ke kiʻekiʻe o ke koena cholesterol kiʻekiʻe. Eia kekahi, ua hōʻike ʻia nā noiʻi mua i nā mea maʻi e lawe nei i nā statins i ka hui pū ʻana o nā lāʻau hoʻohaʻahaʻa TG ʻaʻole e hōʻemi i ka hopena o nā hanana cardiovascular. ʻO kēia mau mea e paʻakikī loa ai ka mālama ʻana i ka hyperlipidemia.
Hoʻoponopono ka ANGPTL3 (angiopoietin-like protein 3) i ka lipid a me ka metabolism lipoprotein, me ka TG a me ka non-high-density lipoprotein cholesterol (HDL-C), ma ke kāohi ʻana i ka lipoprotein lipase, endosepiase, a me ka lipoprotein haʻahaʻa haʻahaʻa (LDL) receptor-dependent hepatic lipoprotein uptake. Ua ʻike ʻia ʻo ka ANGPTL3 inactivation ʻokoʻa alakaʻi i ka hoʻonui lipoprotein lipase a me ka hana endosepiase, ka mea e alakaʻi ai i nā pae lipoprotein plasma haʻahaʻa i ka hapa nui o nā hihia, ʻO kēia nā triglyceride-rich lipoproteins (ie Chylomicrons, koena cholesterol, VLDL, medium density lipoprotein [IDL]), lipoprotein lipoprotein kiʻekiʻe (HDL lipoproteins), lipoprotein kiʻekiʻe. ʻāpana. ʻO ka poʻe Heterozygous e lawe nei i kēia ʻano like ʻole he 40% ka emi ʻana o ka pilikia o ka maʻi atherosclerotic, a ʻaʻole i ʻike ʻia kahi phenotype clinical adverse. Hōʻike ʻia ʻo ANGPTL3 i loko o ke ake, a ʻo nā lāʻau lapaʻau silencing gene e kuhikuhi ana i kāna mRNA, i ʻike ʻia he mau lāʻau liʻiliʻi interfering RNA (siRNA), he lāʻau lapaʻau hoʻohiki maikaʻi no ka hyperlipidemia.
Ma Kepakemapa 12, 2024, ua paʻi ka New England Journal of Medicine (NEJM) i kahi noiʻi ARCHES 2 e hōʻoia ana ua hoʻemi nui ka lāʻau siRNA zodasiran i nā pae TG i nā maʻi me ka hyperlipidemia hui ʻia [1]. ʻO ARCHES-2 kahi hoʻāʻo ʻelua-makapō, hoʻomalu ʻia i ka placebo, ka hoʻāʻo ʻana i ka pae 2b hoʻāʻo. He 204 mau maʻi me ka hyperlipidemia hui ʻia (nā pae TG hoʻokēʻai 150-499 mg/dL, nā pae LDL-C ³70 mg/dL a i ʻole nā ​​pae HDL-C ³100 mg/dL) i kākau inoa ʻia. Ua hoʻokaʻawale ʻia lākou i ka hui zodasiran 50 mg, 100 mg pūʻulu, 200 mg pūʻulu a me ka placebo control group. Ua loaʻa i nā poʻe maʻi nā injections subcutaneous i ka pule 1 a me 12, a loaʻa i ka follow-prophylaxis a hiki i ka pule 36.
ʻO ka hopena mua o ka hoʻololiʻana o ka TG mai ka papa kuhikuhi a hiki i ka wiki 24. Uaʻikeʻia ka haʻawina ma ka wiki 24, ua ho'ēmi nuiʻia nā pae TG i ka hui zodasiran ma keʻano o ka hopena (ua hoʻemiʻia nā kiʻekiʻe o TG i kēlā me kēia hui e ka 51, 57 a me 63 pakeneka, i ka hoʻohālikelikeʻana me ka poʻe i loko o ka hui placebo) (P<0.001 no nā mea a pau. Ua emi pū ka ANGPTL3 e 54 mau pakeneka, 70 pakeneka a me 74 pakeneka. Non-hdl-c pae i emi iho ma 29 pakeneka helu, 29 pakeneka, a me 36 pakeneka, apolipoprotein B pae emi i ka 19 pakeneka, 15 pakeneka, a me 22 pakeneka, a me ka LDL-C ua emi e 16 pakeneka helu, 14 pakeneka helu, a me 20 pakeneka hopena, pakahi aku la, a hiki i ka hopena o keia mau pule. I ka pule 24, zodasiran
Ma 88% o nā maʻi i ka hui 200 mg, ua hāʻule ka TG hoʻokēʻai i ka pae maʻamau.

Hōʻike nā pua ʻulaʻula i nā lā 1 a me 12 i ka zodasiran a i ʻole placebo.

Ua emi iho nā pae TG hoʻokēʻai i ka maʻamau i ka pule 24 (150
mg/dL a emi mai paha)
Hōʻike kēlā me kēia pou i hoʻokahi maʻi.

Ua ʻike pū ʻia ka noiʻi ʻana ua palekana ʻo zotasiran i nā pūʻulu dosis āpau, me 2 wale nō nā mea maʻi i hoʻopau i ke aʻo ʻana ma muli o nā hanana ʻino (1 i ka hui placebo a me 1 i ka hui zotasiran 100 mg). ʻO nā hanana koʻikoʻi koʻikoʻi āpau i ka hui zotasiran i hoʻihoʻi ʻia ma ka hopena o ke aʻo ʻana, a aia hoʻokahi make ma ka hui placebo. ʻO ka hopena ʻino wale nō o ka hopohopo ʻo ka hoʻonui ʻana i ka HBA1c i ka hui zotasiran 200 mg i hoʻohālikelike ʻia me ka placebo (ka hoʻololi ʻana mai ka baseline a hiki i ka pule 24 [± SD], 0.38±0.66% vs. -0.03±0.88% i nā maʻi me ka maʻi diabetes preexisting). ʻO nā maʻi me ka maʻi maʻi ʻole he 0.12±0.19% vs. -0.03±0.19%).
ʻO ka mea nui, kokoke i nā mea maʻi āpau i ka haʻawina (96%) e mālama ʻia me nā statins (37% o ia mau statins kiʻekiʻe), 1% i mālama ʻia me ka proprotein-converting enzyme subtilysin 9 inhibitor (PCSK9i), a me 21% i mālama ʻia me nā fibrates. No laila, ʻo ka hoʻohui ʻana o zodasiran ma ke kumu o ka regimen lapaʻau maʻamau i kēia manawa ua loaʻa i nā hopena hoʻohaʻahaʻa lipid nui, e hāʻawi ana i kahi regimen hou no ka mālama ʻana i ka hyperlipidemia hui ʻia i ka wā e hiki mai ana.
I ka pule 24, ʻo ka nui o ka nui o 200 mg o zotasiran i loko o ke aʻo ʻana i hoʻemi i ke koena o ka cholesterol ma 34.4 mg / dL i hoʻohālikelike ʻia me kahi placebo. Ma muli o nā hiʻohiʻona o kēia manawa, manaʻo ʻia kēia hōʻemi e hōʻemi i nā hanana ʻino ʻino nui ma ka 20 pakeneka. Hiki i ka zodasiran ke hoʻohana ma ke ʻano he monotherapy no nā mea lipoprotein āpau e hōʻemi i ka hopena o nā hanana cardiovascular i nā maʻi. No laila pono ka noiʻi hou e hoʻoholo i ka hiki o kēia lāʻau i ka hōʻemi ʻana i ka hopena o ka maʻi atherosclerotic.
ʻO ka Phase 2b, double-blind, randomized, placebo-controlled MUIR study, i paʻi ʻia i ka manawa like ma NEJM, ua hoʻohana i kahi lāʻau siRNA ʻē aʻe, plozasiran, e mālama i ka hyperlipidemia hui ʻia [2]. Hoʻolālā ʻia ka plozasiran e hōʻemi i ka hōʻike ʻana o APOC3, ka gene encoding apolipoprotein C3 (APOC3), kahi mea hoʻoponopono o ka metabolism TG, i loko o ke ake, a laila e hoʻemi ana i ka pae TG a me ke koena o ka cholesterol. ʻO ka hoʻemi ʻana i ka TG a me ke koena o ka cholesterol i ʻike ʻia ma ke aʻo ʻana ua like ia me nā mea i loaʻa ma ka haʻawina ARCHES-2. No laila, ua manaʻo ʻia i nā mea maʻi me ka hyperlipidemia hui ʻia, ua like nā hopena o nā lāʻau ʻelua i ka hōʻemi ʻana i ke kiʻekiʻe o ka triglyceride-rich lipoprotein a me ke koena cholesterol.
Hōʻike nā hopena o nā haʻawina siRNA ʻelua he papa hoʻohiki maikaʻi loa kēia e lawe mai i nā koho hou no ka mālama ʻana i ka hyperlipidemia hui ʻia a hoʻomaikaʻi i nā hopena cardiovascular i nā maʻi.