Kev ntsuam xyuas kev txhais lus ntawm cov tshuaj Antithrombotic hauv NHP qauv
Cov kab mob thrombotic tseem yog ib qho ntawm cov ua rau mob morbidity thiab tuag thoob ntiaj teb, tsav tsheb nruam nruam hauv kev txhim kho tshuaj tiv thaiv kab mob thiab tshuaj tiv thaiv kab mob. Thaum cov tshuaj anticoagulants ib txwm muaj xws li heparins thiab cov tshuaj tiv thaiv qhov ncauj ncaj qha (DOACs) tau txhim kho kev tswj hwm kev kho mob zoo, kev lav phib xaub tseem yog ib qho kev txwv loj uas txwv tsis pub kho qhov rais thiab ntev - kev nyab xeeb.
Nyob rau hauv xyoo tas los no, cov phiaj xwm tshwm sim nyob rau hauv txoj hauv kev coagulation intrinsic coagulation - tshwj xeeb tshaj yog coagulation Factor XI (FXI) thiab FXIa - tau nyiam ntau yam uas muaj peev xwm ntxiv tom ntej -cov tswv yim antithrombotic tiam. Cov txheej txheem no tsom mus ua kom tau txais txiaj ntsig zoo thrombosis thaum txo qis los ntshav, lub hom phiaj feem ntau hu ua "uncoupling thrombosis los ntawm hemostasis."
Txawm li cas los xij, kev ntsuas kev txhais lus ntawm cov tshuaj anticoagulants tshiab tseem nyuaj. Cov qauv nas thrombosis feem ntau tsis ua tiav tag nrho cov tib neeg coagulation physiology, platelet biology, vascular teb, thiab cov yam ntxwv pharmacodynamic. Yog li ntawd, cov qauv uas tsis yog- tib neeg primate (NHP) thrombosis tau nce ntau dua kev lees paub tias yog cov kev txhais lus tseem ceeb rau kev ntsuam xyuas cov tshuaj tiv thaiv kab mob, coagulation biomarkers, thiab los ntshav ua ntej kev kho mob.
Leveraging nws specializedhematology thiab cardiovascular pharmacology platform, Prisys Biotechnologies tau tsim muaj tus qauv zoo heevcynomolgus liab femoral arteriovenous (AV) shunt thrombosis qauvtsim los rau kev txhais cov kev ntsuam xyuas ntawm anticoagulants, biologics, thiab tshiab coagulation pathway modulators. Lub platform sib koom ua ke kev tshaj lij kev phais, kev soj ntsuam ntau ntawm thrombus, coagulation biomarker tsom xam, thiab kev ntsuam xyuas kev pheej hmoo los ntshav nyob rau hauv kev kho mob ntsig txog NHP.
Translational Challenges in Antithrombotic Drug Development
Lub coagulation system sawv cev rau kev sib koom ua ke ntawm cov vascular endothelium, circulating platelets, coagulation yam, inflammatory mediators, thiab cov ntshav khiav dynamics. Qhov sib txawv me me hauv cov kev no tuaj yeem cuam tshuam loj heev rau kev txhais lus kwv yees thaum siv tshuaj.
Txawm hais tias cov qauv nas thrombosis muab cov txiaj ntsig zoo rau kev siv tshuab, ntau qhov kev txwv txo lawv qhov kev kwv yees tus nqi rau kev kho mob anticoagulant kev loj hlob:
- Tseem ceeb hom sib txawvhauv coagulation factor qhia thiab kev ua haujlwm
- Qhov sib txawv ntawm platelet reactivitythiab thrombin tiam
- Txwv kev sib pivntawm pharmacodynamic biomarkers
- Txo tus nqi kwv yeesrau kev ntsuam xyuas txaus ntshai los ntshav
- Tsis muaj peev xwm ua kom rov tsim dua tshiabhuman vascular intervention txheej txheem
Cov kev txwv no tau dhau los ua qhov tseem ceeb tshwj xeeb rau cov chav kho mob tshiab xws li FXI inhibitors, bispecific antibodies, RNA therapeutics, thiab gene- kho cov txheej txheem tsom rau txoj hauv kev coagulation.
Tsis yog - tib neeg primates muab kev txhim kho kev txhais lus tseem ceeb vim tias lawv txoj kev sib raug zoo rau tib neeg hauv coagulation physiology, hematological tsis, vascular anatomy, thiab tshuaj metabolism. Vim li no, Cynomolgus liab tau siv ntau dua hauv cov kev tshawb fawb thrombosis thiab hemostasis.
Txheej txheem cej luam ntawm Cynomolgus Monkey AV Shunt Thrombosis Model
Tus qauv AV shunt thrombosis yog ib qho zoo -tsim tsim kev txhais lus thrombosis platform tsim los ntsuas ntau npaum li cas thrombus tsim nyob rau hauv kev tswj cov ntshav ntws. Ntawm Prisys Biotechnologies, tus qauv tau ua kom zoo rau kev rov tsim dua tshiab, kev phais mob sib xws, thiab qhov muaj txiaj ntsig zoo kawg nkaus hauv cynomolgus liab.
Kev npaj phais thiab tso catheter
Nyob rau hauv qhov sib sib zog nqus tshuaj loog thiab sterile phais mob, cov hlab ntsha femoral thiab femoral leeg yog phais cais tawm kwv yees li 3 cm hauv qab ntawm thaj tsam inguinal. Ib qho tshwj xeeb tsim AV shunt catheter system uas muaj U- zoo li thrombogenic hlau yog ces muab tso rau hauv cov hlab ntsha thiab cov hlab ntsha. Cov thrombogenic hlau ua raws li qhov chaw tswj rau thrombus tiam thaum cov ntshav ncig los ntawm extracorporeal shunt system.
Ntshav Flow Control thiab Thrombus tsim
Tom qab tso catheter, cov hlab ntsha clamps raug tso tawm kom pib cov ntshav mus tas li los ntawm AV shunt voj. Lub sij hawm ncig yog tswj tau los xyuas kom meej cov txheej txheem thrombus tsim cov xwm txheej thoob plaws pawg sim. Vim tias tiam thrombus tshwm sim nyob rau hauv cov ntshav khiav tsis zoo, tus qauv ua tib zoo ua raws li kev kho mob cov txheej txheem thrombogenic cuam tshuam nrog platelet activation, coagulation cascade pib, thiab fibrin tsim. Muab piv nrog cov kev soj ntsuam zoo li qub, qhov kev ua haujlwm zoo li no muab kev txhais lus ntau dua rau kev ntsuam xyuas cov tshuaj tiv thaiv kab mob.
Quantitative Thrombus Measurement
Thaum xaus ntawm lub sij hawm ncig, cov thrombogenic U- zoo li tus xaim thiab txuas thrombus yog ua tib zoo tshem tawm ntawm lub catheter system. Tom qab maj mam ntxuav cov kua qaub kom tshem tawm cov kua dej ntau dhau, cov thrombus -cov kabmob hlau yog hnyav siv lub siab - kev ntsuas qhov tseeb. Net thrombus qhov hnyav yog xam los ntawm kev rho tawm lub hauv paus hlau hnyav los ntawm tag nrho cov ntsuas qhov hnyav. Qhov ntau ntawm thrombus qhov hnyav qhov kawg ntawm qhov kawg no muab kev ntsuas siab, muaj zog rov ua dua tshiab, koob tshuaj - teb kev ntsuas kev muaj peev xwm, thiab ncaj qha kev tshuaj xyuas pharmacodynamic ntawm kev siv tshuaj tiv thaiv kab mob.
Qhov zoo ntawm NHP AV Shunt Models hauv Kev Txhais Lus Thrombosis Research
- Closer Human Coagulation Biology:Cynomolgus liab nthuav tawm coagulation yam profiles thiab platelet teb zoo heev piv rau tib neeg.
- Clinically Relevant Biomarker Assessment:Tus qauv txhawb kev sib koom ua ke ntawm coagulation biomarker tsom xam, suav nrog aPTT, PT, thiab thrombin tiam cim.
- Dynamic Hemodynamic tej yam kev mob:Tsis zoo li kev simplified hauv vitro coagulation assays, AV shunt system reproduces thrombus tsim nyob rau hauv tas li ntshav txaus.
- Longitudinal Pharmacodynamic ntsuam xyuas:Tus qauv tsis yog -terminal thiab minimally invasive, tso cai rov ntsuas dua.
Daim Ntawv Thov thiab Kev Pom Zoo Yav Tom Ntej
Prisys Biotechnologies txhawb nqa ntau yamkev tshawb nrhiav los ntshav thiab ntshav txhaws. Lawv cov kev pabcuam kev koom ua ke suav nrogKev ntsuam xyuas PK/PDthiab advancedkev kho mob imaging platformkev koom ua ke. Raws li lub teb txav mus rau qhov tseeb anticoagulation thiab lub hom phiaj - xaiv coagulation modulation, qib siab NHP thrombosis platforms tseem tseem ceeb rau kev siv tau tom ntej - tiam tshiab cov tswv yim kho mob ua ntej kev kho mob txhais lus.
FAQ
Q: Tus qauv AV shunt thrombosis yog dab tsi?
A: Tus qauv AV shunt thrombosis yog tus qauv vascular thrombosis uas cov ntshav ncig los ntawm ib qho extracorporeal arteriovenous shunt uas muaj thrombogenic nto, tso cai rau ntau qhov kev ntsuam xyuas ntawm thrombus tsim nyob rau hauv dynamic ntshav txaus.
Q: Vim li cas cynomolgus liab siv hauv kev tshawb fawb thrombosis?
A: Cynomolgus liab sib sib zog nqus zoo sib xws nrog tib neeg nyob rau hauv coagulation txoj kev, platelet biology, vascular anatomy, thiab pharmacokinetics piv nrog nas hom, txhim kho kev txhais lus kwv yees.
Q: Vim li cas FXI suav hais tias yog lub hom phiaj tiv thaiv kab mob txaus nyiam?
A: FXI ntseeg tau tias yuav pab txhawb rau cov kab mob thrombosis ntau dua li qhov qub physiological hemostasis, ua rau nws lub hom phiaj zoo rau kev txo qis kev pheej hmoo ntawm thrombosis thaum txo qis los ntshav.
