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I-Elafibranor (GFT505) Powder-The New Drug for NASH Treatment Study

Yini i-Elafibranor (GFT505)?

I-Elafibranor (GFT505) powder (923978-27-2), umuthi wokuhlola ocwaningo lwawo lusaqhubeka. Kakhulu, ukutadisha nokuthuthukiswa kwayo yiGenfit kususelwa ekusebenzeni kwe I-Elafibranor (GFT505) powder (923978-27-2) ekulweni nezifo ezinjenge-non-alcoholic fat onesifo sesibindi, i-dyslipidemia, ukumelana ne-insulin, kanye nesifo sikashukela.

I-Elafibranor (GFT505) indlela yokusebenza

I-Elafibranor (GFT505) powder iyindlela yokwelapha esebenza ngomlomo esebenza kuma-subtypes amathathu we-PPAR. Kubandakanya i-PPARa, i-PPARd, ne-PPARg. Kodwa-ke, isebenza kakhulu nge-PPARa.

Indlela yokusebenza ye-Elafibranor iyinkimbinkimbi njengoba ihlukanisa ngokwezifiso ama-cofactors kwi-receptor yenuzi. Njengomphumela, lokhu kuholela emgqumeni wokuhlukaniswa kwezakhi zofuzo kanye nomphumela wezinto eziphilayo.

I-Elafibranor (GFT505) i-powder iyakwazi ukukhomba futhi ifake uphawu lomsebenzi okhethiweyo we-receptor modulator (SNuRMs). Ngenxa yalokhu, inikeza ukusebenza okuthuthukile nemiphumela emibi encishisiwe.

Womabili ama-molecule we-multimodal ne-pluripotent akhombisile ukuthi ayasebenza ekulweni nezimo ezahlukahlukene. Kubandakanya ukumelana ne-insulin nesifo sikashukela, ukuvuvukala, ukukhuluphala ngokweqile, ne-lipid triad, okubonakala ngokwanda kwe-cholesterol ye-HDL kanye nokwehliswa kwe-cholesterol ye-LDL ne-triglycerides.

Umehluko phakathi kwendlela yokusebenza ka-Elafibranor kanye nezinye izinhlanganisela ezihlose ama-PPARs e-NASH (nonalcoholic steatohepatitis) iqiniso lokuthi alibonisi noma yimuphi umsebenzi we-PPARy wemithi.

Ngenxa yalokho, I-Elafibranor abasebenzisi abayitholi imiphumela emibi engafuneki ehlotshaniswa nokwenza kusebenze kwe-PPARy. Imiphumela emibi enjalo ifaka phakathi; ukugcinwa kwe-fluid, i-edema, kanye nesisindo sazo zonke ezikhulisa ubungozi bomuntu ekuhluphekeni kwenhliziyo.

I-Elafibranor (GFT505) yesifundo sokwelashwa kweNash

NASH (nonalcoholic steatohepatitis) yisifo sesibindi esiholela ekuqhekekeni nasekuwohlokeni kwama-hepatocytes kanye nokuqongelelwa kwamafutha okwaziwa nangokuthi yi-lipid amaconsi. Imvamisa, izimo ezithile zezempilo ezinjenge-metabolic syndrome, isifo sikashukela sohlobo 2, kanye nokukhuluphala kuyimbangela yokuqala yesifo esingelotshwala i-steatohepatitis (NASH), kanye nesibindi samafutha esibindi (NAFLD).

I-Elafibranor (GFT505) Powder-The New Drug for NASH Treatment Study

Namuhla, abantu abaningi bahlushwa yilesi sifo esibulalayo. Ingxenye ethusayo ngakho ukuthi kungaholela ku-cirrhosis, isimo esenza isibindi singakwazi ukusebenza. Kungathuthuka futhi kumdlavuza wesibindi futhi kwezinye izimo, kubangele ukufa.

Izindaba ezidabukisayo nge-NASH (nonalcoholic steatohepatitis) ukuthi ayithathi iminyaka futhi iyaqhubeka nokuthinta wonke umuntu. Okubi futhi, izimpawu zezifo zingaba yi-asymptomatic, futhi umuntu angaze azi ukuthi bahlaselwa yilesi sifo kuze kube yilapho sebekhulile kakhulu.

Ukulimala nokulimala okulethwe yi-NASH (i-nonatocoholic steatohepatitis) kungahle kuholele ezinkingeni zenhliziyo nemaphaphu. Njengoba kunabantu abaningi abahlaselwe yilesi simo esisuka kwisifo esinamafutha esibindi esingelona utshwala, abacwaningi bafuna ezinye izindlela zokwelashwa ngaphandle kokufakelwa isibindi.

Enye yezidakamizwa ezifundelwa ukwelashwa kwe-NASH yi-Elafibranor (GFT505) powder (923978-27-2). Kuze kube manje, kukhombisile ukudala imiphumela emihle ezicini ezimbili eziphambili zalesi sifo, ie, ukubhalaza nokuvuvukala. Ubuhle obunayo ukuthi iyabekezeleleka kakhulu futhi ngeke yenze umuntu ahlupheke nganoma iyiphi imiphumela emibi. Kungenxa yalesi sizathu ukuthi i-US Food and Drug Administration inikeze ukubizwa okusheshayo kwalesi sidakamizwa Ukwelashwa kwe-NASH.

Njengamanje, i-Elafibranor (GFT505) i-powder ekuvivinyweni kwemitholampilo kwesiGaba 3, nayo ebizwa ngokuthi yi-HLOLA IT.

HLOLA-IT

Kuyisifundo somhlaba wonke esiqale ngekota yokuqala yonyaka we-2016, engahleliwe, esilawulwa yi-placebo ngokulawulwa 2: 1 nokungaboni kabili. Iziguli ezibandakanyeka kulolu cwaningo yilezo ezihlushwa i-NASH (NAS> = 4) kanye ne-fibrosis (F2 noma F3 izigaba lapho ukulimala kwesibindi sekuvele kuphawuleka. Kuyo lonke lolu cwaningo, iziguli zizonikezwa umthamo we-Elafibranor (GFT505) I-120mg noma i-placebo kanye ngosuku.

Iziguli zokuqala eziyinkulungwane ezizobhaliswa zizosiza ukukhombisa ukuthi ngabe i-NASH yelashwa nge-Elafibranor (GFT505) ngaphandle kokuqina kwe-fibrosis uma iqhathaniswa naleyo ephethwe nge-placebo.

Iqembu lokuqala labhaliswa ngo-Ephreli 2018, kanti ukucutshungulwa kwemiphumela kuzobikwa ngasekupheleni kuka-2019. Imininingwane ebikiwe izonquma ukuthi ngabe i-Elafibranor ivunywa yini yi-US Food and Drug Administration njengoba ithola imvume yezomthetho yi-European Medicines Agency, kahle eyaziwa ngokuthi i-EMA ngo-2020.

Ucwaningo luqhubekele phambili ngoDisemba 2018 lapho i-Data Safety Monitoring Board (DSMB) ivuma ukuqhubeka kwecala ngaphandle kokushintshwa. Lokho kwakungemva kokubuyekezwa kwangaphambi kokuhlelwa kwedatha yokuphepha eyenziwe ngemuva kwezinyanga ezingamashumi amathathu.

I-Elafibranor (GFT505) Powder-The New Drug for NASH Treatment Study

Imiphumela yocwaningo lwangaphambi kokuhlola kanye nezifundo zokwelapha ekwelashweni kwe-NASH

Ukusebenza kanye nokuphepha kwe-Elafibranor ekwelashweni kwe-NASH kuhlolwe esikhathini esidlule ngokusebenzisa amamodeli ezifo amaningi. Esigabeni 5a 2a, kwenziwa izilingo ezahlukahlukene kubantu abahlukahlukene abaguliswa yisifo se-metabolic. Kubandakanya nalabo abanesifo sikashukela sohlobo 2 noma isifo sikashukela kanye ne-atherogenic dyslipidemia. Ngesikhathi sokufunda, kwabonwa ukuthi u-Elafibranor uyakhuthaza;

  • Inciphise ingozi yokuhlushwa yizinkinga zenhliziyo
  • Amamaki ancishisiwe wokulimala kwesibindi
  • Izici zokulwa nokuvuvukala
  • Ukwanda kokuzwela kwe-insulin
  • I-glucose homeostasis
  • Iphrofayili ye-lipidoprotective lipid.

Isivivinyo sesigaba 2b esaqalwa ngonyaka we-2012 sasiyisivivinyo esikhulu kakhulu sangaphakathi kanye nocwaningo lwangempela lokuqala olwenziwa e-NASH. Kungaleso sikhathi lapho u-Elafibranor athola khona umbono ophakanyisiwe we-FDA wokuqedwa kwe-NASH ngaphandle kokukhula kwe-Fibrosis. "Lokho bekuyiso isiphetho esiyinhloko sokuqulwa kwecala 3 lesigaba esisaqhubekayo.

Kwabonakala ukuthi iziguli ezathola ukwelashwa kwe-NASH nge-Elafibranor zaphawula ukuthuthuka kwezimpawu zokungasebenzi kahle kwesibindi ezinjenge-ALP, GGT, ne-ALT. Ngokuhlola izindlela zokugcina zesibili, kwabonwa ukuthi i-Elafibranor (GFT505) umthamo we-120mg wanika imiphumela yokwelashwa ezintweni eziyingozi zenhliziyo ezihambisana ne-NASH, Bafaka;

  • Imiphumela yokulwa nokuvuvukala
  • Ukuthuthukiswa kokuzwela kwe-insulin kanye ne-glucose metabolism ezigulini ezinesifo sikashukela
  • Thuthukisa amazinga we-lipoproteins kanye ne-plasma lipids.
Ukusebenza kwe-Elafibranor ekwelapheni i-NASH yezingane

Izinga izingane ezihlushwa ukukhuluphala ngalo likhuphuke kakhulu, okwenza kwaba nokukhathazeka ngezempilo okukhona. Ocwaningweni olwenziwe ngonyaka we-2016, kwaqapheleka ukuthi NAFLD(isifo sokudla kwesibindi esinama-nonalcoholic) sithinta cishe i-10-20% yabantu abengane. Kubuye kwaveza ukuthi i-NAFLD yezingane ingaba yimbangela ehamba phambili yokwehluleka kwesibindi, i-pathology yesibindi, kanye nokufakwa kwesibindi ezinganeni nakwintsha.

NgoJanuwari 2018 bekunokwethulwa ngokusemthethweni kohlelo lwabantwana be-NASH benombono wokuthi i-Elafibranor yiyona kuphela izidakamizwa esefakazelwe ukuthi iyasebenza ekwelashweni kwe-NASH kubantu abadala futhi esesigabeni sokuthuthuka ekwelashweni kwezingane.

Ngabe i-Elafibranor ingasetshenziswa kanye nezinye izidakamizwa ekwelashweni kwe-NASH?

Sekucacile ukuthi i-Elafibranor iyasebenza ekwelashweni kwe-NASH uma isetshenziswa ngokwayo. Kodwa-ke, ngenxa yobunzima bokugula, bungasetshenziswa kanye nezinye izidakamizwa ekuphathweni kwe-fibrosis yesibindi, i-NASH, kanye nokubumbana kwabo ngokubambisana.

I-Elafibranor (GFT505) okunye ukusetshenziswa

Ekwelashweni kwezifo ze-cholstasis

I-cholesterasis yisimo esidalwa ukungahambi kahle ekwakhekeni kwe-bile nokugeleza kwayo gallbladder ne-duodenum. Kungaholela ekwandeni kwesifo se-systemic kanye nesifo sesibindi, ukwehluleka kwesibindi, kanye nesidingo sokudluliselwa kwesibindi. Ucwaningo lomtholampilo olwenziwe lukhombisa ukuthi i-Elafibranor (GFT505) powder inciphisa abamaki be-biochemical ku-plasma yingakho ifakazela ukuthi ingaba wusizo ekwelapheni isifo se-cholestasis.

Diabetes

Isifo sikashukela yisimo esidalwa ukuthi sinoshukela omningi noma ushukela egazini. Ithinta cishe abantu abangamakhulu amane emhlabeni jikelele. Umuntu uba nesifo sikashukela sohlobo 2 uma imizimba yabo ingakwazi ukukhiqiza nokusebenzisa i-insulin ngokujwayelekile.

Ucwaningo olwenziwe ku-elafibranor lukhombisa ukuthi kunciphisa ukuqhubeka kwesifo sikashukela sohlobo 2 ngezindlela ezimbili. Owokuqala ngokusebenzisa ukuthuthukiswa kwe-glucose metabolism emzimbeni.

Kuphinde kuthuthukise ukuzwela kwe-insulin emisipha nasezithanjeni zangaphakathi.

I-Elafibranor (GFT505) Powder-The New Drug for NASH Treatment Study

Isiphetho

Isifundo se-Elafibranor siza njengezindaba ezinhle kunoma ngubani ohlushwa i-NASH. Njengoba sesinikezwe iziguli ezingaphezu kwamakhulu ayisishiyagalombili kuze kube manje futhi sibonisa ukuthi siyasiza, sethemba ukuthi abantu ngeke besadinga ukufakelwa isibindi.

Kwakungekho Ukusebenzisana kwezidakamizwa kwe-Elafibranor kutholakale ne-sitagliptin, i-simvastatin, noma i-warfarin, okubonisa ukuthi yayingasetshenziswa kanye nezinye izidakamizwa ngokuphephile. I-Elafibranor ibekezelelwa kahle emzimbeni futhi ayikhombisi noma yimiphi imiphumela emibi.

Okubhekwayo

  1. Izindlela Zokuhumusha Zokuhumusha kwisifo sikashukela, i-Obesity, neNonalcoholic Fatty, ehlelwe ngu-Andrew J. Krentz, uChristian Weyer, uMarcus Hompesch, uSpringer Nature, ikhasi 261
  2. Ama-PPAR ku-Cellular and - i-Whole Body Energy Metabolism ahlelwe nguWalter Wahli, uRob Tee, ngo-457-470
  3. I-Obesity and Gastroenterology, Indaba Yemitholampilo yaseGastroenterology yaseNyakatho, i-Octavia Pickett-Blakely, uLinda A. Lee, ikhasi 1414-1420

Okuqukethwe

2019-07-23 supplements
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