NHP AV-Shunt Thrombosis Model Rau Kev Ntsuas Tshuaj Tiv Thaiv Kev Nyab Xeeb|Prisys Biotech - Xov Xwm

Kev txhim kho ntawm tom ntej no - tiam antithrombotic therapeutics -tshwj xeeb yog monoclonal antibodies tsom coagulation yam xws li Factor XI (FXI)- yuav tsum muaj kev ntsuam xyuas meej ntawm qhov sib npaug ntawm cov tshuaj tiv thaiv kab mob thiab los ntshav. Qhov kev ntsuam xyuas dual no tseem yog qhov tseem ceeb hauv kev txhim kho preclinical, tshwj xeeb tshaj yog rau biologics nrog cov txheej txheem nyuaj ntawm kev ua.

Tsis yog -tib neeg primates (NHPs) muab cov qauv kev txhais tau zoo heev vim lawv txoj kev sib raug zoo ntawm lub cev rau tib neeg hauv ob qho tib si coagulation thiab kev tiv thaiv kab mob. Vim li ntawd,NHP-raws li qauvtau raug suav tias yog cov cuab yeej tseem ceeb rau kev kwv yees qhov tshwm sim ntawm kev kho mob ntawm cov tshuaj tiv thaiv kab mob -raws li kev kho mob.

Prisys Biotech uses NHP AV-shunt thrombosis and bleeding models to evaluate efficacy and bleeding risk of novel antibody therapeutics targeting coagulation pathways

Prisys Biotechnologies, AAALAC- tau lees paub lub koom haum tshawb fawb kev txhais lus, tau tsim lub platform muaj zog rau kev ntsuam xyuas los ntshav thiab thrombosis txaus ntshai hauv cynomolgus liab. Nws cov AV sib xyaw ua ke -shunt thrombosis thiab venous bleeding qauv tau txhawb ntau qhov kev xa tawm IND thiab pab txhawb rau cov phooj ywg- tshuaj xyuas cov ntawv tshaj tawm, ua rau kev tshawb fawb nruj thiab kev tswj hwm- kev txiav txim siab raws nraim - ua.

Kev soj ntsuam ntau ntawm Antithrombotic Efficacy: NHP AV-Shunt Model

Covarteriovenous (AV) shunt thrombosis qauvHauv NHPs ua rau tib lub sijhawm ua haujlwm ntawm thawj thiab theem nrab hemostasis, suav nrog ob qho tib si platelet aggregation thiab coagulation cascade dynamics. Qhov kev ua kom muaj ob txoj hauv kev no ua rau nws tsim nyog rau kev soj ntsuam cov tshuaj tiv thaiv kab mob biologics.

Nyob rau hauv cov tshuaj loog, ib qho kev tswj hwm extracorporeal Circuit Court yog tsim los ntawm cov hlab ntsha femoral thiab femoral leeg. Cov ntshav raug tso cai los ntawm lub shunt rau ib lub sij hawm, feem ntau 15 feeb, thaum lub sij hawm uas thrombus tsim tshwm sim ntawm tus txheej txheem substrate (xws li, phais xov). Lub thrombus- cov khoom siv thauj khoom yog muab sau, qhuav, thiab hnyav.

Thawj qhov chaw tshuaj tshuaj muaj zog kawg -net clot luj-yog xam los ntawm kev rho tawm qhov hnyav ntawm lub substrate. Qhov kev ntsuas ntau npaum no muab qhov rhiab heev thiab koob tshuaj - nyob ntawm qhov ntsuas ntawm cov tshuaj tiv thaiv kab mob, ua kom pom tseeb qhov sib txawv ntawm cov neeg sib tw kho mob thiab kev siv tshuaj.

Qhov tseem ceeb, tus qauv no tau pom tias muaj zog rov tsim dua tshiab thiab muaj txiaj ntsig ntawm kev txhais lus, txhawb nqa nws siv hauv kev tswj hwm kev xa tawm.

Parallel Evaluation of Bleeding Risk: Forearm Vein Bleeding Model

Txhawm rau ua kom tiav qhov kev ntsuam xyuas kev ua tau zoo, tus qauv qauv forearm vein bleeding model yog ua haujlwm los ntsuas qhov kev pheej hmoo los ntshav raws li kev tswj xyuas.

Ib qho me me, rov tsim dua qhov kev txiav yog tsim nyob rau hauv lub forearm vein, thiab cov ntshav yog maj mam nqus los ntawm cov ntawv lim tsis siv lub siab rau lub qhov txhab. Lub sij hawm los ntshav thiab tag nrho cov ntshav poob yog kaw nrog siab precision.

Piv nrog rau cov qauv ib txwm muaj xws li tus Tsov tus tw transection los yog ntiv tes los ntshav, txoj hauv kev no txo qis kev hloov pauv thiab txhim kho rov ua dua.
Nws tso cai rau kev ntsuas serial ntawm ntau qhov kev tshaj tawm - lub sijhawm koob tshuaj, ua kom cov ncauj lus ntxaws ntxaws ntawm cov teebmeem ntawm lub cev ntawm cov tshuaj tiv thaiv kab mob ntawm hemostasis.

Cov yam ntxwv no muaj txiaj ntsig tshwj xeeb rau biologics nrog ntev ib nrab -lub neej lossis qeeb cov lus teb pharmacodynamic.

Integrated Clinical Pathology thiab Coagulation Analysis

Ntxiv nrog rau qhov kawg ntawm vivo, cov kev ntsuam xyuas dav dav hauv vitro coagulation tau muab tso ua ke los muab kev nkag siab txog kev siv tshuab thiab txhawb kev txhais lus.

Ntawm Prisys, cov kev tshuaj ntsuam no feem ntau suav nrog kev saib xyuas kev ua haujlwm ntawm ib feem ntawm thromboplastin lub sij hawm (aPTT) thiab lub sij hawm prothrombin (PT), nrog rau kev sib hloov thromboelastometry (ROTEM) rau qhov tiag - lub sij hawm ntsuam xyuas ntawm cov hlab ntsha kinetics, nrog rau lub sij hawm ua kom ntshav (CT) thiab lub sij hawm txhaws (CTFT).

Lub hom phiaj -kev soj ntsuam tshwj xeeb ntawm kev ua haujlwm- xws li FXI/FXIa inhibition- ntxiv rau kev soj ntsuam ncaj qha ntawm kev siv tshuaj, cuam tshuam qhov sib txawv ntawm qhov tshwm sim thiab cov txiaj ntsig ua haujlwm.

Cov ntaub ntawv sib xyaw ua ke no txhawb kev ntseeg siab hauv ob qho tib si kev ua tau zoo thiab kev nyab xeeb profiling, tshwj xeeb tshaj yog rau kev tswj hwm kev sib cuam tshuam.

Kev Txhais Lus Case Study: Anti-FXI Antibody Development

Tus nqi txhais lus ntawm lub platform no tau pom nyob rau hauv kev sib koom tes nrog cov koom tes ua lag luam. Nyob rau hauv ib tug neeg sawv cev txoj kev kawm uas muaj xws li ib tug anti-FXI monoclonal antibody (xws li, BJTJ-1837), NHP AV-shunt qauv tau lees paub muaj zog, koob tshuaj tiv thaiv ntawm kev tsim cov thrombus.

Pharmacodynamics and pharmacokinetics of BJTJ- 1837 in cynomolgus monkeys. Cynomolgus monkeys were treated with 5 mg/kg of BJTJ-1837 intravenously. Blood samples were collected at indicated time points after dosing. Plasma concentration of BJTJ-1837 (μg/mL, blue diamond, the plasma concentration at Day 35 & Day 42 is below detection limit), aPTT (% to predose, red triangle), FXI:C (% to predose, magenta circle), and free FXI (μg/mL, green square) were plotted against time. The total plasma concentration of BJTJ-1837 and free FXI concentration were quantified using ELISA as described in supplementary materials and methods. aPTT, activated partial thromboplastin time; F, factor. — Pharmacodynamics thiab pharmacokinetics ntawm BJTJ-1837 hauv cynomolgus liab. Cynomolgus liab tau kho nrog 5 mg / kg ntawm BJTJ-1837 intravenously. Cov ntshav tau sau tseg ntawm lub sijhawm teev tom qab noj tshuaj. Plasma concentration ntawm BJTJ-1837 (ug / mL, pob zeb diamond xiav, plasma concentration ntawm Day35 & Hnub 42 yog qis dua kev kuaj pom), aPTT (% rau predose, daim duab peb sab liab), FXI: C (% rau predose, magenta vajvoog), thiab dawb FXI (ug / mL, ntsuab square) tau npaj rau lub sijhawm. Tag nrho cov ntshav plasma concentration ntawm BJTJ-1837 thiab dawb FXI concentration tau suav nrog ELISA raws li tau piav qhia hauv cov ntaub ntawv ntxiv thiab cov txheej txheem. aPTT, qhib ib nrab thromboplastin lub sijhawm; F, yam.

Qhov tseem ceeb, cov nyhuv antithrombotic no tau ua tiav yam tsis muaj qhov cuam tshuam los ntawm kev pheej hmoo los ntshav hauv tus qauv forearm leeg. Cov kev tshawb pom no qhia txog qhov muaj peev xwm kho tau ntawm FXI- cov tswv yim los cuam tshuam kev tiv thaiv thrombosis los ntawm cov teeb meem los ntshav.

Cov txiaj ntsig ntawm kev tshawb fawb tau luam tawm tom qab hauv Kev Tshawb Fawb thiab Kev Xyaum hauv Thrombosis thiab Haemostasis, qhia txog kev ntseeg tau ntawm cov qauv thiab nws cov txiaj ntsig.

Xaus

Kev koom ua ke ntawm covNHP AV-shunt thrombosis qauvnrog rau kev ntsuam xyuas los ntshav raws li tus qauv thiab cov kev ntsuam xyuas coagulation ua ke muab lub zog muaj zog thiab kev txhais lus muaj feem cuam tshuam rau kev ntsuam xyuas cov tshuaj tiv thaiv kab mob -raws li kev kho mob antithrombotic.

Nrog rau cov txheej txheem kev khiav hauj lwm, kev tsim tawm siab, thiab ntau IND- ua kom muaj kev paub dhau los, Prisys Biotechnologies txhawb nqa cov koom tes biopharmaceutical thoob ntiaj teb hauv kev ua kom coagulation{1}} tsom rau cov kev kho mob los ntawm kev txhim kho preclinical mus rau kev ua tiav kev kho mob.

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FAQ

Q: Vim li cas NHP cov qauv nyiam rau kev soj ntsuam cov tshuaj tiv thaiv kab mob antithrombotic?

A: NHPs sib koom siab physiological thiab molecular zoo sib xws nrog tib neeg hauv txoj hauv kev coagulation thiab tiv thaiv kab mob, ua rau lawv muaj kev kwv yees ntau dua li cov qauv nas rau biologics, tshwj xeeb tshaj yog monoclonal antibodies.

Q: Dab tsi ua rau AV-shunt qauv txhais lus cuam tshuam?

A: Tus qauv AV-shunt ib txhij ua kom cov platelet sib sau ua ke thiab coagulation cascades nyob rau hauv kev tswj cov dej ntws, ze ze rau tib neeg cov txheej txheem thrombosis thiab ua kom muaj kev soj ntsuam ntau ntawm cov tshuaj ua tau zoo.

Q: Yuav ua li cas los ntshav kev pheej hmoo raug soj ntsuam nrog rau kev siv tshuaj tua kab mob?

A: Kev pheej hmoo los ntshav yog raug soj ntsuam siv tus qauv forearm vein bleeding model, uas ntsuas lub sij hawm los ntshav thiab ntshav. Txoj kev no tso cai rau kev ntsuas rov ua dua thiab muab kev ntsuam xyuas txhim khu kev qha ntawm cov tshuaj - ntxias hemostatic impairment.