Kev tshawb nrhiav mob ntsws asthma: Vim li cas ho tsis yog - Tib neeg Primate Models Yog Pivotal Rau Novel Drug Development

Mob hawb pob, tus kab mob ua pa ntev thoob plaws ntiaj teb, nthuav tawm cov kev xav tau kev kho mob tseem ceeb vim nws qhov nyuaj, suav nrog kev tsis muaj kev kho mob thiab kev ua tau zoo tshaj plaws hauv qee cov neeg mob. Cov qauv tshuaj preclinical feem ntau poob luv luv hauv kev kwv yees qhov ua tau zoo ntawm kev kho mob, qhia txog qhov xav tau sai rau cov qauv zoo tshaj plaws uas zoo dua rov qab los ntawm tib neeg cov kab mob kom txhawb nqa cov tshuaj kho mob hawb pob tshiab. Kab lus no elucidates tus nqi tseem ceeb ntawmTsis yog-Human Primate (NHP) qauv, tshwj xeeb tshaj yog cynomolgus liab, hauv kev ua kom cov txheej txheem R&D tseem ceeb no.

Kev mob ntsws asthma yog tus cwj pwm los ntawm cov yam ntxwv tseem ceeb ntawm pathophysiological xws li mob ntsws ntsws o, ua pa nyuaj siab (AHR), thiab kev txwv tsis pub rov qab los. Tus kab mob nthuav tawm qhov tseem ceeb heterogeneity, nrog rau ntau yam phenotypes xws li kev tsis haum tshuaj thiab tsis yog - mob hawb pob uas tau tsav los ntawm cov txheej txheem sib txawv. Cov kev kho mob hawb pob tam sim no, xws li nqus tau corticosteroids (ICS) thiab 2-agonists, feem ntau tswj cov tsos mob tab sis feem ntau tsis muaj kab mob- hloov cov teebmeem, thiab ib qho ntawm cov neeg mob hawb pob hnyav tseem kho tau. Qhov no heterogeneity yuav tsum tau preclinical qauv muaj peev xwm los xav txog ntau yam kab mob subtypes.

Tsis yog-Human Primate (NHP) qauvraug suav hais tias yog tus choj txhais lus zoo tshaj plaws ntawm kev tshawb fawb preclinical thiab kev sim tshuaj ntsuam xyuas vim tias lawv cov kab mob lom neeg zoo sib xws rau tib neeg. Hauv kev mob ntsws asthma thiab lwm yam kev tiv thaiv kab mob - cov kab mob inflammatory, NHPs muaj qhov zoo sib xws:

• Cov Txheej Txheem Zoo Tshaj Plaws Zoo:NHP cov txheej txheem tiv thaiv kab mob, tshwj xeeb yog T-cov lus teb ntawm tes, cytokine profiles, thiab IgE- cov tshuaj tiv thaiv kab mob sib kis, tau txais txiaj ntsig zoo nrog tib neeg. Qhov no yog qhov tseem ceeb heev rau kev ntsuam xyuas cov kev kho mob immunomodulatory tshiab zoo li biologics.
• Similar Respiratory Anatomy thiab Physiology:NHP txoj hlab ntsha hauv lub cev, cov qauv tsim, lub ntsws parenchyma, thiab cov lus teb rau bronchoconstrictors zoo ib yam li cov tib neeg. Qhov zoo sib xws no txhim kho qhov chaw kho mob ntawm cov kev tshawb fawb txog kev kho cov hlab cua, qhov mob, thiab hyperresponsiveness.
• Peev Xwm rau Tus Qauv Kab Mob Ntev:NHPs tuaj yeem tsim kho mob hawb pob phenotypes los ntawm qhov ntev - kev ua xua rau lub sijhawm, ua tib zoo ua raws li qhov ntev ntev thiab rov tshwm sim ntawm tib neeg mob hawb pob.

Cynomolgus liab, ib hom NHP uas nquag siv, muab cov txiaj ntsig tshwj xeeb hauv kev tshawb nrhiav mob ntsws asthma:

• Susceptibility thiab Phenotype Induction:Cynomolgus liab yog raug rau cov allergens (piv txwv li, ovalbumin - OVA) thiab muaj peev xwm rhiab heev thiab nyuaj rau induce typical allergic asthma phenotypes, xws li AHR, airway o, thiab mucus hypersecretion.
• Kev Txhais Lus PK/PD Kev Kawm:Lawv cov caj ces ze dua thiab lub cev zoo ib yam li tib neeg pab txhawb kev txhais lus ntawmPharmacokinetic (PK)thiabpharmacodynamic (PD)cov ntaub ntawv.
• Superior Recapitulation:Muab piv rau cov qauv nas, uas muaj qhov sib txawv tseem ceeb hauv txoj kev tiv thaiv kab mob, lub ntsws architecture, thiab kev txwv tsis pub muaj peev xwm ua kom tag nrho cov kev hloov pauv ntawm txoj hlab ntsws ntev, cynomolgus liab qauv zoo dua simulate complex pathophysiology ntawm tib neeg mob hawb pob.

Prisys Biotechmuaj nplooj siab xav muab siab -NHP qauv zoo thiab cov kev pabcuam tshawb fawb ua ntej rau ntau yam kev kho mob, suav nrog cov kab mob ua pa. Peb lub xeev 4,000 m²- ntawm- lub- art facility nyob rau hauv Shanghai lub tsev muaj peev xwm NHP tseem ceeb thiab tau nruab nrog kev kho mob- qib ntsuas, suav nrog CT, MRI, Doppler ultrasound, endoscopy, laminar flow surgical suites, thiab ICU, txhua yam tsim los txhim kho cov ntaub ntawv txhais lus.

Prisys Biotechtau tsim cov qauv NHP rau cov kab mob ua xua, suav nrogTus qauv asthma hauv cynomolgus liabinduced los ntawm rhiab heev thiab kev sib tw nrog ovalbumin (OVA) ntxiv rau adjuvant. Cov qauv no yog tsim los simulate cov yam ntxwv ntawm atopic dermatitis (AD), kev tsis haum rhinitis (AR), thiab mob hawb pob nrog kev ua tau zoo thiab kev tsim tawm.

Peb cov qauv muab cov ntsiab lus ntsuas qhov kawg rau kev ntsuas kev ua tau zoo:

• Kev ntsuam xyuas lub ntsws ua haujlwm:Nrog rau kev ntsuam xyuas ntawm txoj hlab pa hyperresponsiveness (AHR), piv txwv li, siv acetylcholine (ACh) kev sib tw rau PC50 kev txiav txim siab, cuam tshuam txog kev ua pa hauv pa.
• Bronchoalveolar Lavage Fluid (BALF) Analysis: Cytology los soj ntsuam inflammatory cell infiltration (xws li eosinophils, lymphocytes, neutrophils) thiab kom muaj nuj nqis ntawm cov inflammatory cytokines tseem ceeb (xws li, IL-4, IL-5, IL-13, IFN-).
• Kev ntsuam xyuas Serological: Kev soj ntsuam tag nrho thiab OVA-IgE cov qib tshwj xeeb, cuam tshuam qhov kev siv zog ntawm cov tshuaj tiv thaiv kab mob ua xua thiab ua kom muaj txiaj ntsig zoo.
• Mob ntsws Histopathology:Kev ntsuam xyuas ntawm cov yam ntxwv tseem ceeb xws li inflammatory cell infiltration, mucus hypersecretion (goblet cell hyperplasia), thiab airway phab ntsa thickening, qhia txog kev kho cov hlab cua.

Prisys Biotech Covcynomolgus asthma qauvtuaj yeem siv los ntsuas ntau yam kev kho mob ntsws asthma tshiab, suav nrog tab sis tsis txwv rau:

• Biologics tsom rau cov cytokines tshwj xeeb (xws li, anti-IL-5, anti-IL-4R, anti-IgE).
• Novel inhaled formulations los yog tshuaj molecule me.
• Immunomodulators, gene therapies, thiab mRNA-raws li kev kho mob.

Prisys Biotechhais txog cov txheej txheem txheej txheem los xyuas kom meej cov ntaub ntawv ntseeg tau thiab rov tsim dua tshiab. Los ntawm kev koom ua keAdvanced duab(piv txwv li, CT rau kev soj ntsuam lub ntsws) thiab cov txheej txheem tshwj xeeb xa cov tshuaj (xws li, nebulization, bronchoscopic instillation), peb tus qauv cynomolgus hawb pob muab siab -cov ntaub ntawv zoo, cov ntaub ntawv muaj feem cuam tshuam, ua kom nrawm rau kev txhim kho preclinical ntawm txoj kev kho mob hawb pob.

Xaus

Raws li peb txoj kev nkag siab txog kev mob hawb pob tob zuj zus, qhov kev thov rau cov qauv ua ntej nrog kev txhais lus zoo dua tuaj. NHP qauv, tshwj xeeb tshaj yog cynomolgus liab, yog qhov tseem ceeb hauv kev tshawb nrhiav tshuaj kho mob hawb pob.Prisys Biotech, nrog nws cov kws tshaj lij NHP qauv platforms, cov chaw ua haujlwm siab heev, thiab muaj peev xwm ntsuam xyuas tau zoo, tau cog lus los muab kev pabcuam kev tshawb fawb txog kev ua haujlwm tau zoo thiab meej txhawm rau txhim kho cov tshuaj ua pa thoob ntiaj teb.