I-HDL ye-Synthetic: I-Plaquebuster? Okanye Bust Just?

I-HDL yoHlangano

Njengokuba wonke umntu uyazi, i-cholesterol ye-HDL "yi-cholesterol enhle," kuba amazinga e-HDL aphakanyisiwe ahambelana nobungozi obuncitshiswa bokugula komzimba. I-HDL idlala i-cholesterol engaphezu kweetyhuse kwaye ibuyisela kwisibindi ukuze iqhutywe. Ngako-ke, abaphandi baye bachitha iminyaka emininzi bezama ukuphucula unyango oluya kwandisa amazinga e-HDL, kwaye ngaloo ndlela lukhulise inkqubo yokususa i-cholesterol "embi".

Le migudu sele ididekile.

Enye indlela yophando eyake yabonakala iyona nto iyithembisayo kwindawo ye-HDL mimetics-ifom ye-HDL "efana" nefuthe le-ApoA, i-HDL lipoprotein.

Yintoni i-HDL Mimetics?

Njengazo zonke iipoprotein, ii-HDL zincinci (kule imeko, i-cholesterol), kunye neeprotheni ezikhethekileyo ezithutha i-lipid ngegazi. Iiprotheni ezenza i-HDL lipoproteins yintsapho yeeprotheni ezibizwa ngokuthi yiAAA. I-ApoA yiyona "isithako esisebenzayo" ye-particle ye-HDL. Yiyo i-ApoA eqokelela i-cholesterol engaphezu kweendonga ze-arterial kwaye iyithwala. Ngoko i-cholesterol ye-HDL esilinganiselayo ngeemvavanyo zegazi yi-cholesterol eye isuswe kwiisishu, kwaye isendleleni yokubuyela kwisibindi ukuze iqhutywe.

Ngoko ke, kunengqiqo ukuba ukuba sinokwandisa inani leeprotheni ze-ApoA kwigazi lethu sinokunyusa inkqubo yokususwa kwe-cholesterol, kwaye mhlawumbi, ukunciphisa umngcipheko wokuphucula i-atherosclerosis.

Ii-mimetics ze-HDL ziyizidakamizwa ezilinganisa, ngokubanzi ngokusemandleni, iiprotheni ze-ApoA. Ziyasebenza esebenzayo iindidi ze-HDL. Zininzi ziphuhliso, kodwa uphando nophuhliso lwenkqubo luye lucotha kwaye luyeka.

Amava nge-HDL Mimetics

Amava okuqala ekliniki ene-HDL mimetic yabikwa ngo-2003.

I-HDL imimetic ebizwa ngokuthi yi-ApoA-1 Milano, elawulwa njengamayeza angama-5 e-intraveous engama-weekly, yabangela ukunyanyiswa okukhulu kweeplathi kwiindawo ezincinci zamadoda ane-coronary artery disease. (Isixa sokutshatyalaliswa okwenene sasincinane, kodwa kwakunokutshatyalaliswa, kwaye kwakubaluleke kakhulu.)

I-ApoA-1 Milano yafunyanwa ngokufunda abantu abangama-40 bevela kwidolophu encinane e-Italiya ababeyaziwa ngokuhlala ubomi obude kunye nobunempilo, nangona bekunciphise amanqanaba e-HDL. Abaphandi bafumanisa ukuba aba bantu babehlobo lwe-HDL (i-ApoA-1 Milano) engazange ifumaneke ngokuhlolwa kwegazi rhoqo, kodwa oko kwabonakala kusebenza kakhulu ekukhuseleni izifo zentliziyo. Abaphandi bakwazi ukulungelelanisa ukuguqulwa kwe-DNA eveze le HDL entsha, kwaye yongezelela le DNA entsha kwi-bacterium ye-laboratory, -kudala "ifowuni" yokuveliswa kwe-ApoA-1 Milano.

Olu pho nonongo luye lwaluvuyisa kakhulu phakathi kweengcali ze-cardiologist kwaye, ngenxa yeengxelo zendaba, phakathi koluntu jikelele.

Kodwa kwiminyaka edlulayo siye sava ngasemva malunga ne-ApoA-1 Milano.

Kukho umsebenzi omninzi kwimvelaphi, nangona kunjalo. Amalungelo kwi-ApoA-1 Milano ashintshile ngezandla eziliqela, kwaye iinkampani ezininzi zamachiza ziyaziwa zisebenza kwi-HDL mimetics.

Kodwa ngoku kubonakala kucacile ukuba inkqubo yokuphuhlisa la machiza kukuba, kuncinci, kunzima kwaye kuyabiza.

Ngaphezulu, ngo-2014 i-mimetic yesibili ye-HDL (CER-001, esuka kwiCerenis Therapeutics) yavavanywa kwilingo lekliniki elibizwa ngokuba yi-CHI-SQUARED, kwaye lahluleka ukubonisa inzuzo ekunciphiseni imiqulu yeplate.

Uphi i-HDL Mimetics Yima ngoku?

Inzondelelo iyancipha kakhulu ukususela ngo-2003. Ezi ziyobisi zibonakaliswe nzima kakhulu ukuphuhlisa nokuvelisa, kwaye zisekelwe kwiziphumo ze-CHI-SQUARED azinakulungele ukuba zisebenzise yonke indawo. Ngoxa singenakukwazi ngokuqinisekileyo, kubonakala ngathi iinkampani ezinkulu zeziyobisi ziye zawayeka.

Ziye zaphuhliswa ngamakhampani amancinci anezinto ezincinci.

Ukongezelela, inzondelelo enkulu yabaphandi ekukhuliseni amazinga e-HDL njengendlela yokukhusela isifo senhliziyo sele iyancipha kakhulu kwiminyaka yamuva nje, ukungaphumeleli okuphawulekayo kwe-CETP inhibitors njenge-torcetrapib, kwaye kungekudala, i-niacin. Iinkampani zeziyobisi ziye zachitha iibhiliyoni zizama ukufumana iziyobisi ezandise amazinga e-HDL kunye nokunciphisa isifo senhliziyo, kungabi nantoni na. Abaxolisi baqala ukubuza yonke "i-HDL hypothesis," oko kukuthi, amazinga aphezulu e-HDL ahlala efanelekileyo.

Ngoko i-HDL yokwenziwa komculo isaphantsi kophuhliso kwaye ingaba yinto eninzi yokwenza amayeza. Kodwa kukho umsebenzi omningi omele ukwenziwa. Kwaye nangona le migudu igxotha, lolu hlobo lwesilwanyana kufuneka lugcinwe (kwii-doses eziye zazimiselwa kunye nezikhathi ezithile); kwaye inike iminyaka yokusebenza kunye nemali esetyenzisiwe, sinokulindela ukuba ezi ziyobisi zichithwe ngokukhawuleza. Ngoko asifanele sibaphefumle.

Okukwintsusa

Indlela efanelekileyo yokunyusa amazinga ethu e-HDL kukusebenzisa indlela yokuphila enempilo. Le ndlela inenzuzo yokunciphisa umngcipheko wethu kungakhathaliseki amazinga ethu e-HDL.

Imithombo:

I-Tardif JC, i-Ballantyne CM, uBarter P, et al. Iimpembelelo ze-high-density lipoprotein i-agent ye-mimetic i-CER-001 kwi-coronary atherosclerosis kwizigulane ezinama-coronary syndromes. European Heart Journal. 29 uEpreli 2014 I-DOI: http://dx.doi.org/10.1093/eurheartj/ehu171

I-Nissen SE, i-Tsunoda T, i-Tuzcu EM, kunye ne-al. Impembelelo ye-ApoA-I Milano ephindaphindiweyo kwi-coronary atherosclerosis kwizigulane ezine-coronary syndromes eziphambili. JAMA 2003; 290: 2292.