Kupfuura jini: Kutarisa neuroinflammation muHuntington's disease

Dr. Rajeev Kumar: Zvinofadza kuva pano. Ndatenda

Dr. Sarah Camargos: Saka kunyange hazvo HD ichikonzerwa nekuchinja kwemajini kwakanyatsotsanangurwa, pane kuzivikanwa kuri kukura kwekuti kuzvimba kweuropi kunogona kubatsira mukufambira mberi kwechirwere. [00:01:00] ANX005 iantibody inorwisa C1q, chikamu chenzira yekuwedzera. Ungatsanangura muchidimbu kuti nei system yekuwedzera ichikosha muchirwere cheHuntington?

Dr. Rajeev Kumar: Zvakanaka, ndatenda nemubvunzo. Sisitimu yekuwedzera chinhu chatakadzidza nezvacho vazhinji vedu kuchikoro chekurapa, uye tinoiona sechikamu chemhinduro yekudzivirira hutachiona. Inoisa zviratidzo zvehutachiona nemasero akakuvara kuti abvise utachiona. Asi muuropi, inogadzirwa munharaunda, uye ine basa rakasiyana zvachose.

Munguva yekukura kwakajairika, mapuroteni ekuwedzera, kunyanya C1q iri pamusoro pe cascade, anoisa synapses yakawandisa kuitira kuti microglia igone kuichekerera, uye izvozvo zvine hutano uye chikamu chemaitiro anoita uropi kunatsiridza masero europi akajairwa. Zvisinei, muHD, system yekuchekerera inoita seinodzoserwa patsva, uye kune basa rakanaka kwazvo repreclinical, kunyanya bepa raWilton nevamwe vake vekuNature Medicine kubva muna 2023, iro rinoratidza kuti muHuntington models, C1q inoisa cortico-striatal [00:02:00] synapses.

Zvadaro microglia inodzibvisa, wobva warasikirwa nekubatana kwacho pakutanga, uye izvi zvinoteverwa nezviratidzo zvepakutanga muHD. Uye izvi zvinosimbiswa nehumbowo hwemunhu mushure mekufa kwekuti tinoona kuti muuropi hweHuntington, tinoona zvikamu zve classical complement zvakakwira pa synapse. Uye zvechokwadi, kana tikatarisa varwere, CSF complement activation markers dzakadai seC4a dzakakwira, uye kukwirira kunoenderana nekufambira mberi kwechirwere uye danho rechirwere.

Saka pane humbowo hwekuti complement haisi chinhu chinongoratidza kuzvimba kwetsinga chete, asi inogona kunge iriyo inokonzeresa kuchekererwa kwemasero etsinga uye inosimudzira kufambira mberi kwezvirwere kuvarwere vazhinji.

Dr. Sarah Camargos: Kune vanachiremba vasiri vanachiremba vezvirwere zvemuviri, zvinorevei kudzivirira C1q mukushanda? Sei C1q yakasarudzwa senzira yekurapa?

Dr. Rajeev Kumar: Ehe. Mukutaura kwechokwadi, complement cascade iketani reaction, [00:03:00] uye C1q iri pamusoro chaipo. Ndiyo molecule yekuzivikanwa. Kana yangobatana kune chinangwa, zvese zvinoitika pasi pemvura zvichifamba. Uye ANX005 iantibody yemonoclonal inosunga C1q, kudzivirira kuti isatange cascade. Iye zvino, tinoda kutanga kumusoro kwete pasi pemvura nekuda kwezvikonzero zviviri.

Chekutanga, kana ukavhara C1q, unodzivirira synaptic tagging panobva. Pane kuedza kubvisa zvese mushure mekunge tagging yatoitika uye wava kutokuvara, unogona kudzivirira tagging iyoyo. Uye chechipiri, inosarudza zvakanyanya. Sisitimu ye complement ine maoko akawanda. Ine nzira ye classical complement, asi inewo nzira dze alternative ne lectin, asi idzi dzinobatana zvakanyanya paC3.

Saka, kana ukavhara paC3, unodzima zvese zvinoitwa nekuwedzera simba rekudzivirira chirwere, izvo zvinogona kukuisa panjodzi huru yehutachiona. Nekungovhara ruoko rwekare rwekuwedzera simba rekudzivirira chirwere, tiri kusiya dzimwe nzvimbo idzodzo dzisina chirwere, uye tiri kutevera nzira yekurapa yatinofunga kuti ndeyekuchekerera chirwere, uye tinosiya nzira yekurapa nekuchengetedza nzvimbo yacho isina chirwere.

Ndinovimba kuti izvozvo zviri pachena [00:04:00]. Tinoda kuwana synaptic tagging uye kudzivirira uropi hwakakura hunokonzera kuzvimba.

Dr. Sarah Camargos: Saka unoderedza mhedzisiro isiri iyo, handiti? Uchiita izvi.

Dr. Rajeev Kumar: Ehe. Uye zvechokwadi, mukudzidza kwedu uye mune zvimwe zvidzidzo zvikuru zvakatevera-- zvidzidzo zvakawanda zvakaitwa neiyi ANX-003, iyo yava nezita rinonakidza rinonzi Tanruprubart. Ehe, ndiro zita racho nekuti ikozvino riri pamberi peFDA neEuropean Medical Association kuti ribvumidzwe chirwere cheGuillain-Barré.

Nekuda kweizvi, hatina kuona hutachiona hwakakomba hune chekuita nekudziviswa kwekushanda kwekuwedzera kwemasero eropa nekutarisa C1q. Saka ichocho chinhu chakanaka chekuchengetedza.

Dr. Sarah Camargos: Saka chidzidzo chako chinoshuma zera reCAG chigadzirwa kana CAP score. Ungatsanangura here kuti nei chiyero ichi chinomiririra pakudzidza vatori vechikamu uye vatori vechikamu vasati vaongororwa vane chirwere cheHuntington?

Dr. Rajeev Kumar: Ehe. Zvakanaka, chigadzirwa cheCAP kana CAG age, inzira yekubata kuratidzwa kwehupenyu hwese kune chepfu yemutant huntingtin senhamba imwe chete [00:05:00]. Saka pfungwa ndeyekuti mutoro wechirwere unoenderana nehuwandu hwekuwedzera kweCAG. Kudzokorora kwenguva refu kune chepfu yakawanda uye kunokonzera chirwere chekare, uye kuti munhu agara kwenguva yakareba sei achisangana nazvo.

Saka CAP inowedzera zvinhu izvi pamwe chete. Nguva, kuoma kwekukura kunowedzera zera, uye kana kuri pamusoro pemuganhu, munhu anowanzova nezviratidzo. Saka zvakaita semakore akawanda ekuputa fodya. Zviri nyore. Uye zvechokwadi, iyi inzira yakanaka yekuwedzera hupfumi kuvanhu vedu vanotanga kuoneka kana kuti vanononoka kutanga zviratidzo zvechirwere, uye mukati menguva yatinofunga kuti tinogona kuyera kufambira mberi kwechidzidzo chipfupi uye kuwedzera hupfumi kuvarwere vanogona kubatsirwa nekurapwa.

Dr. Sarah Camargos: Ndapota titungamirirei kuburikidza nemhedzisiro uye ongororo dzekudzidza kwenyu.

Dr. Rajeev Kumar: Ehe. Iyi inyaya yekudzidza yechikamu chekutanga che "multi-center", yakavhurika, ine ruoko rumwe chete. Saka munhu wese akawana mushonga unoshanda. Hapana placebo. Takanyoresa varwere makumi maviri nevasere. [00:06:00] Zvakare, makumi mapfumbamwe muzana akazviratidza, gumi muzana akanonoka kuonekwa. Munhu wese akasimbiswa nemajini, uye akachengetedza mashandiro emuviri. Saka mamakisi ekuzvimirira aive makumi masere kubva muzana.

Pakutanga, varwere vaipiwa mushonga wekuwedzera weawa makumi maviri nerimwe waiitwa zvishoma nezvishoma kuitira kuderedza mukana wemigumisiro yakaipa, yatinogona kutaura nezvayo nhasi. Murwere akapihwa mushonga wechipiri, waipiwa nekukurumidza pamazuva mashanu kana matanhatu, uye kutanga pamavhiki maviri mushure mekupindira, vaipiwa mushonga wekuwedzera mavhiki maviri ega ega kusvika pavhiki makumi maviri nemaviri.

Varwere vakazotevera nguva dzose kuti vaone kana paine migumisiro yakaipa uye kushanda kwayo, pamwe chete nezviratidzo zvemishonga nemakemikari pavhiki makumi maviri nemana, makumi maviri nemasere, uye makumi matatu nematanhatu. Saka vaive nenguva yekurapwa kwemavhiki gumi nemaviri, makumi maviri nemana, uye pakati pevhiki makumi maviri nemana nemakumi matatu nematanhatu, nguva yekuzorora kwemavhiki gumi nemaviri.

Uye izvozvo zvainakidza chaizvo. Uye zvinangwa zvikuru, hongu, zvaive kuchengetedzeka uye kushivirira, pharmacokinetics yemushonga mu serum neCSF. Uye zvino isu [00:07:00] tinoda kutsvaga zviratidzo zve pharmacodynamic zvekusangana kwechinangwa, mazinga eC1q, zviratidzo zvekuwedzera zvakaita seC4a, C3, C3a, pamwe neNfL sechiratidzo chekukuvara kwe neurofilament.

Saka takaitawo basa rekuongorora rekurapa, iro rainakidza zvikuru. Saka takaongorora Composite Unified Huntington's Rating Scale, kana kuti cUHDRS, nezvikamu zvayo. Inosanganisira Total Functional Capacity score, Symbol Digit Modality score, Stroop word reading, uye zvakare, hongu, Total Motor score.

Saka CUHDRS ipfungwa yakabatana inobatanidza zvese izvi zviyero zvekushanda kwemuviri nepfungwa muchiyero chimwe chete, uye inoenderana zvakanaka nekudzikira kwebasa pamwe nekushaya simba kweuropi. Saka hatina kuita zviyero zvekufungidzira muchidzidzo ichi, asi chinhu chatiri kufunga nezvacho muchidzidzo chinotevera.

Dr. Sarah Camargos: Uye ndezvipi zvakawanikwa zvakanyanya maererano nekuchengetedzeka uye kubatanidzwa kwezvinangwa?

Dr. Rajeev Kumar: Ehe. Saka ngatitangei tataura nezve target engagement [00:08:00]. Saka tinozadza C1q mu serum neCSF kubva pakutanga chaipo, nguva yekutanga yekuyera, inova pamavhiki matanhatu. Uye target engagement iyi yakaramba iripo munguva yese yekurapwa uye yakazodzikira zvishoma nezvishoma munguva yekusarapwa. Saka huwandu hwemishonga yeCSF hwakanga hwakaderera, hunongova .2 - .25 muzana.

Uye ndizvo chaizvo zvataizotarisira ne monoclonal antibody inopihwa neIV. Asi paive nezvakakwana zvakapfuura nepakati peropa neuropi zvekuti takaona pharmacodynamic effect. Uye zvinonakidza ndezvekuti kana wawana C1q yakazara, inotanga chiyero che target effect, izvo zvinoreva kuti C1q yakazara inokonzera fracture yeC4a.

Izvi hazvisi pamusoro penyama, saka hazvikuvadzi. Saka chiratidzo. Uye izvi zvinogona kunge zviri izvo zvinokonzera mamwe maitiro ane chekuita nekuiswa kweropa, ayo ndichataura nezvawo munguva pfupi iri kutevera. Uye takaonawo kudzikira kukuru mu [00:09:00] zviratidzo zve [00:09:00] zvekushanda kwekuwedzera kwesimba, zvakaita seCSF, C3, uye C3a.

Uye kuvandudzika uku muzviratidzo izvi zvakaramba zviripo kusvika panguva yekusapihwa mushonga. Zvino, panyaya yekuchengetedzeka, pane zvinhu zviviri zvikuru. Chimwe ndechekuti paunopa mushonga, murwere wese ane maitiro akafanana neanopihwa mushonga, uye izvozvo zvinonakidza uye zvinoshamisa. Uye ndicho chikonzero nei mushonga wekutanga uchitora maawa makumi maviri nerimwe kuti upiwe mushonga...

Ehe. Saka husiku hwese. Hazvisi nyore kuita nekuti kana ukaramba uchiita zvishoma nezvishoma, hauzonyanyi kurwara zvakanyanya, uye unotora mushonga weH1 neH2 blockers, acetaminophen, pamwe ne corticosteroids. Uye izvi zvinoderedza kuoma kwechirwere, icho chinonyanya kuva maculopapular rash.

Uye zvinokwenya, zvinovava, uye vamwe vanhu vanozobuda ropa. Izvi zvinogoneka. Hazvina kunyanya kuipa. Varwere vazhinji vanowana reaction yegiredhi rekutanga kana rechipiri, uye zvinopera. Uye chinonakidza ndechekuti izvi zvinoita se [00:10:00] pseudoallergy ine chekuita nekushanda kwe complement kunoitika. Yeuka kuti fluid phase reaction yandataura, C4 kuenda kuC4a, imwe anaphylactoid iri kuburitswa, kwete IgE mediated.

Uye kutaura chokwadi, kana wangowana C1q yakazara, iyo inoitika nedosi yekutanga iyoyo, hauzoioni nedosi dzinotevera. Ndosaka mamwe madosi achigona kupihwa nekukurumidza nekuti unenge watova neC1q yakazara. Hauwane maitikiro aya ane chekuita neinfusion. Saka ichocho chinhu chinonakidza chaizvo, uye chinonyatsoenderana nemaitiro ekuita.

Imwe nyaya inokosha yekuchengetedza ndeyezviitiko zvinokonzeresa njodzi dzekurapa, zvimwe zvacho zvinogona kunge zvakakomba. Saka takaona chiitiko che autoimmune muvarwere vaiva ne ANA yepamusoro. Saka mumwe murwere akawana lupus-like syndrome, mumwe munhu akawana ruminatus, uye mumwe munhu aive ne autoimmune hemolytic anemia.

Zvese izvi zvakagadziriswa nekumira kurapwa uye/kana kurapa — Semuenzaniso, murwere aive nechirwere che lupus-like syndrome akarapwa nekushandisa ma steroids uye [00:11:00] hydroxychloroquine. Izvi hazvishamisi nekuti pane humbowo hunoratidza kuti varwere vane kushomeka kwezvikamu zvekutanga zvekuwedzera senge C1q vanogona kubatwa ne lupus.

Zvinokonzera izvi. Muzvidzidzo zvemangwana, tinofanira kuva nekutarisa kwakasimba kweANA uye zvichida kubvisa varwere vane ANA positive uye vachiramba vachitarisa zvingangoitika zve autoimmune. Nekuti iyi yaive ongororo pfupi; varwere vaingotora mushonga kwemavhiki makumi maviri nemana chete. Zvinogoneka kuti pangave nezviitiko zvakawanda zve autoimmune zvine kudzvinyirirwa kwenguva refu, uye ichocho chinhu chinofanira kuongororwa muzvidzidzo zvechikamu chechitatu.

Dr. Sarah Camargos: Ehe, asi ndinoyeuka, makayera maantibody eANA mune ese pakutanga aive pasi pe160.

Dr. Rajeev Kumar: Ehe. Vanhu vatatu vane hutachiona, kunyangwe hushoma, vanogona kukonzera kana kuti vanogona kubatwa nechirwere ichi. Saka zviri muvarwere vatatu ivavo chete. Saka izvozvo zvinoita sechiratidzo chakajeka. Saka izvi zvinofanira kufungwa nezvazvo, ndinofunga [00:12:00], sezvo kushandiswa kwemushonga uyu kuchigona kupararira zvakanyanya, semuenzaniso, muGuillain-Barré syndrome kana mune zvimwe zvirwere zvinoderedza mashandiro etsinga uko kuzvimba kwetsinga kungave kuri kukonzera izvi.

Dr. Sarah Camargos: Paiva nezviratidzo zvebiomarker zvaiita sezvine tariro here kune miedzo yeramangwana? 

Dr. Rajeev Kumar: Ehe, zvaifadza chaizvo nekuti takaona kuti danho rekutanga rekushanda kwe complement kana complement activity rakayerwa ne ratio ye C4a kusvika ku C4 ratio rairatidza kuti kurapwa kwacho kwaizoshanda sei. Saka C4a chiratidzo chekuti nzira yekare ye complement a- inoshanda sei, uye yakakwira muvarwere vane manifest Huntington.

Sezvandambotaura, zvinoita sekunge zvine chekuita nekufambira mberi kwechirwere uye danho rechirwere. Saka kana tikapatsanura varwere vane chiyero chepamusoro cheC4a kusvika kuC4 tochienzanisa nechikamu chidiki, tinogona kuona mutsauko. Varwere vaiva nechiyero chepamusoro, chinoratidzika kunge chakanyanya kukuvara kwetsinga kana kuti kushanda kwekuwedzera, [00:13:00] vairatidza kubatsira kwekiriniki.

Uye tinogona kushandisa izvozvo kupatsanura bvunzo inotevera uye pamwe nekuwedzera huwandu hwevanhu vedu kuti vakwanise kuedza inotevera. Uye zviratidzo zveC4a zvinokurudzira kuwedzera nekudzora C3a, C neC3 zvaive zvakakosha. Vakasimbisa kuti mushonga unoita zvatinoda kuti uite. Uri pachinangwa, unoshanda, uye une simba rinogara kwenguva refu mukudzora kushanda kwemushonga.

Chimwe chinhu chatakaodzwa mwoyo nacho ichiedza che neurofilament. Chakaramba chakasimba zvechokwadi. Zvechokwadi, ndingati, chakanga chisina ruzivo pano. Chidzidzo chipfupi, mavhiki makumi maviri nemana chete. Tinoziva kuti muHD, kune kusiyana kwakawanda kwemazinga eNfL pakati pevarwere.

Kuchinja kweNfL kwakaderera muHD, kwakasiyana neALS, uko kunogona kucherechedzwa zvakanyanya. Uye, kwave kune dzimwe nzira dzekurapa, semuenzaniso, muALS, dzakaratidza kuti huwandu hweNfL hunogona kuderedzwa. Hatina kuona izvozvo pano. Chinhu chatinofanira kufunga nezvacho mukudzidza kwakakura uye kwenguva refu [00:14:00], uye zvinoita kuti ndifunge kuti tinofanira kuvimba zvakanyanya nezviyero zvekufungidzira zveMRI sechiratidzo chechipiri chemhedzisiro patinoita bvunzo yePhase III double-blind, placebo-controlled.

Dr. Sarah Camargos: Zvakanaka. Kunyangwe ichi chiri chidzidzo chekuchengetedza, pane zviratidzo zvekiriniki zvawakawana zvichikurudzira here, kunyanya pachikamu ichi chevarwere vane chiyero cheC4/C4a? 

Dr. Rajeev Kumar: Ehe, zvechokwadi. Basa iri repamusoro-soro rekuwedzera, sezvamakataura, kune vanhu avo vakagadzikana kana kuvandudzika mukati memavhiki makumi maviri nemana ekurapwa, uye izvi zvakaramba zviripo kusvika panguva yekusarapwa, nepo boka remabasa mashoma rakaderera zvakanyanya pamwe chete neboka renhoroondo yezvisikwa rakatorwa, semuenzaniso, kubva muchidzidzo cheTRACK-HD.

Uye, kana ukatarisa varwere ivavo vane chiitiko chepamusoro chekuwedzera simba remuviri, vanhu vanosvika 75% vakavandudzika, nepo 36% chete yechikamu chidiki chechikamu chekuwedzera simba remuviri chakavandudzika. Uye izvi zvaive zvakafanana pamatanho ekushanda, zviyero zvepfungwa [00:15:00], pamwe nemabasa ekufambisa muviri.

Saka izvozvo zvakanaka. Uye pakava nekuvandudzika pakupera kwevhiki rechitanhatu, zvichiratidza kuti izvi hazvisi kudzvinyirirwa kwekuora kwetsinga, asi paive nekugona kununurwa kwema neuron nema synapses asina kushanda zvakanaka asi asati afa nekubvisa C1q kubva muma synapses iwayo. Ma synapses iwayo anorwara, tichaadaidza kuti, zvino ava kushanda zvakanyanya, uye paive nekuvandudzika kwezviratidzo.

Tinofanira kuona zvinoitika nekurapwa kwenguva refu maererano nekugona kudzvinyirira kuora kwetsinga dzemuviri. Asi ndinofunga kuti tinofanira kutaura zvakajeka uye takatendeseka. Ichi chaive chidzidzo chidiki, chakavhurika, ruoko rumwe chete, pasina placebo, uye ongororo yevanopindura yandakataura pakati pechiitiko chepamusoro nechakaderera chekuwedzera yaive ongororo ye post hoc.

Kunyange hazvo, vaongorori, varwere, nevatsigiri vese vakapofumadzwa nekuti ongororo iyoyo haina kuitwa kusvika chidzidzo chapera. Saka izvozvo zvakanaka uye zvinondipa chivimbo nezvazvo. Uye mhedzisiro yacho pamatanho akasiyana-siyana ekurapa yaive yakafanana, uye izvozvo zvinondipa chivimbo chakawanda.

Asi, [00:16:00] chidzidzo chidiki. Zvinofungwa nezvehuwandu hwenyaya ndezvokuti, izvi zvaive zvakakosha muhuwandu hwenyaya. Takaita kuenzanisa kwakawanda kwehuwandu hwenyaya, uye pakanga pasina kugadziriswa kwekuenzanisa kwakawanda. Saka tinofanira kuva vakatendeseka uye kuziva miganhu yekudzidza kwedu, asi chidzidzo chikuru chinopa pfungwa.

Zvinotipa chivimbo chekuenderera mberi nekudzidza kukuru. Izvi zvakabatsira kuratidza pfungwa yezvehupenyu, zvakadaro.

Dr. Sarah Camargos: Uye unofunga here kuti kudziviswa kwekuwedzera kwechirwere kunogona kushandawo padanho rekupedzisira rechirwere, kwete chete kuHuntington yekutanga?

Dr. Rajeev Kumar: Ehe, ndinofunga kuti zvinogoneka zvechokwadi. Asi, nzira inoshanda nayo inoratidza kuti tinofanira kuenda nekukurumidza. Kutaura zvazviri, kunyangwe kusvika padanho rekutanga rezviratidzo nekuti tinoziva kuti pane kuiswa kwekutanga kwekuwedzera. Tine synapses dzakawanda uye ma neuron akawanda ekuchengetedza. Uye kuvandudzwa kwekutanga kwezviratidzo kunoratidza kuti tinogona kununura ma neuron anoshanda uye anorwara, asi asati afa [00:17:00]. Saka tinoda kufanotaura kare tisati tarasikirwa nema synapses nema neuron. Zvino, izvo hazvirevi kuti hatigone kuva nehukama hunobatsira muchirwere chepadanho rekupedzisira, asi zvese izvi zvinoratidza kuti pamwe tinofanira kuenda nekukurumidza pane gare gare. Ndinofunga kuti tinoda kushandisa ISS ikozvino kunyoresa varwere mumatanho akasiyana-siyana, sezvo kurapwa uku kuchigadzirwa. Asi ndinofunga kuti kuyedzwa kwekutanga kukuru kunodzorwa ne placebo kunofanirwa kuitwa muvarwere vane chirwere chekutanga kana chirwere chekupedzisira. Unoziva, ISS danho rekutanga rechitatu, danho rechipiri, danho rekutanga rekupedzisira. 

Dr. Sarah Camargos: Ko system yekuwedzera simba ndiyo inonyanya kuratidza kuora kwetsinga here, kana kuti unotenda kuti ndiyo inotungamira kufambira mberi kwechirwere? 

Dr. Rajeev Kumar: Ndinofunga kuti pane humbowo hwakawanda hwekuti imutyairi kwete kuva munhu anomira, tichazvidaidza kudaro. Saka kana tikatarisa humbowo hwepamberi pekiriniki, muHuntington models, kana tikavhara C1q, inochengetedza synapses uye inoponesa zvikanganiso zvepfungwa. Uye tinogona kuona kuti complement activation uye [00:18:00] synaptic targeting zvinoitika kare, uye kurasikirwa nesynapse kunoita sekunge kunoitika kare, kwete senzira yekunonoka chete.

Uye zvakare, takaona kuti varwere vaive nekushanda kwakanyanya kwekuwedzera kwesimba remuviri ndivo vakapindura. Saka izvi zvinoratidza kuti chikamu chechikonzero kwete kungoongorora chete. Chidzidzo chedu ichi, chinopa muenzaniso wakavimbika unowedzera kuwedzera kwesimba remuviri, asi tinofanira kusimbisa izvi mukudzidza kukuru, kwenguva refu zvechokwadi. 

Dr. Sarah Camargos: Zvechokwadi. Ndeipi nhanho inotevera yekuziva kana nzira iyi ichinyatsochinja kufambira mberi kwechirwere? Unotaura nezve MRI neurofilament, nguva yakareba...

Dr. Rajeev Kumar: Ndinofunga kuti tinofanira kuita zvese izvozvo. Tinofanira kuita saizi inodzorwa ne placebo isina kurongeka. Inofanira kunge yakareba zvakakwana. Inofanira kuita zvinhu zvakawanda. Tinofanira kutarisa mazinga e cUHGRS uye kuyera. Inoderera neinenge poindi imwe pagore. Mhedzisiro ine zvayakanakira mukiriniki inogona kunge iri kuderera makumi maviri, makumi matatu muzana.[00:19:00] 

Saka ndingati tinoda chidzidzo chemwedzi gumi nemisere, makumi maviri nemana. Tinofanira kufanotaura nekuwedzera ruzivo rwevarwere vane mabasa akawanda ekuwedzera ruzivo uye kuisa miganhu kuburikidza neizvozvo. Pamwe simba kubva kuboka iri repamusoro re biomarker. Uye, tinofanira kusanganisira kwete chete zviyero izvi zvekuwedzera ruzivo, NfL, asi MRI yehuwandu, ndinofunga inodiwa.

Saka iyi ndiyo ongororo. Zvichada basa rakawanda kuti zviitwe. Zvichada zviwanikwa zvakawanda. Ndinovimba kuti tichazviita. Uye ndinofunga kuti Eneaxon, mutsigiri, anofarira kuzviita. Ehe, zviwanikwa zvinodiwa zvakawanda. Eneaxon ikambani diki. Ndinovimba kuti chikumbiro chavo che, muGuillain-Barré syndrome chichatenderwa. Kambani ichatanga kuva nechigadzirwa chakatenderwa, chinova mushonga uyu. Tichava nemari yekudyara mari kuti tiwane chiratidzo muHuntington. Ngativimbei nazvo. 

Dr. Sarah Camargos: Ko kuwedzera kwekudzivirira kunogona kubatanidzwa nemishonga yekudzikisa tin here? 

Dr. Rajeev Kumar: Zvakanaka, ndinofunga kuti zvine musoro zvikuru. Zvinonzwisisika zvechokwadi. Kudzikiswa kweHuntingtin [00:20:00] kunotevera mutyairi wemajini ari kumusoro, handiti? Puroteni yehuntingtin yakachinja, kuwedzera kwemuviri, ndicho chikonzero chikuru. Kudzivirira kwekuwedzera kunoshanda pasi, kuchidzivirira synapses kubva kumigumisiro inokuvadza yemutyairi wemajini. Mukushanda kwe microglial, tinofanira kufunga nezvazvo. Kushanda kwe microglial kunotungamirirwa ne mutant huntingtin. Izvozvo zvinogona kuburitsa C1q, iyo inoratidza synapse, iyo inotanga iyi cascade inozvisimbisa. Kana tikakwanisa kudonhedza mutant huntingtin, uye zvakare tinogona kukanganisa kushanda kwe microglial uye kuderedza C1q-mediated aberrant synaptic pruning.

Tinogona kurwisa mafundo maviri akasiyana panguva imwe chete uye zvine simba guru. Asi, kusanganisa mishonga miviri kwakaoma zvikuru. Ndinofunga kuti tinofanira kuratidza kushanda zvakanaka mukurapa kwekudzikisa tin. Tiri padanho iroro nedata reUniQure razvino. Ngatitarisirei kuti tibvumidzwe ipapo. Uye, ndinofunga kuti tinofanira kuratidza kushanda zvakanaka kwekurapa kwe anti-C1q, tobva tazvibatanidza. 

Dr. Sarah Camargos: [00:21:00] Zvakanaka. Munoona here kuti nzira iyi yekurapa ichashandiswa kune zvimwe zvirwere zvinokanganisa mashandiro etsinga, sezvamakataura, sezvazvaive kuna Guillain-Barré? 

Dr. Rajeev Kumar: Ehe, ndinofunga kuti pane tariro yakawanda ingave iripo nekuti pane humbowo hwekuti kupruning kwakanyanya kwe synaptic kungave kuripo. Semuenzaniso, muchirwere cheAlzheimer's, pane humbowo hunoratidza kuti C1q inonyora synapses kunyangwe ma plaque asati aitika.

Kana ukavhara nzira iyoyo, unogona kudzivirira kurasikirwa nesynapse uye pamwe zvinhu zvakaita seAPOE, TREM2 zvinosimbisa izvozvo. Parkinson ine zvimwe zvinobatanidzwa mushure mekufa uye biomarker. MuALS, kune huwandu hwekuwedzera hunowanikwa pamasero etsinga dzemuviri, asi kune humwe humbowo muALS hungave husiri chiratidzo chikuru, kunyanya pakutanga, pamwe gare gare. Kugadzirisa kwakakosha.

Saka ndinofunga kuti, zvinovimbika kuti kune varwere vakasiyana kana mapoka evarwere mukati mezvirwere zve neurodegenerative izvo zvinotsigira activation chinhu chakakosha. [00:22:00] Iyi nzira yekutanga yekuyera kwekuwedzera kwesimba inogona kuva nzira yekuwana varwere ivavo uye pamwe kuita miedzo mumapoka iwayo ega ega mukati mezvirwere zvakasiyana zve neurodegenerative.

Saka ndine tariro. 

Dr. Sarah Camargos: Neniwo. Ehe, uku kuchiri kutsvagurudza kwekutanga, saka mibvunzo mipfupi yaive yekuchengetedzeka, kubatanidzwa kwezvinangwa, zviratidzo zvebiomarkers, uye kana miedzo mikuru yekudzora inogona kuratidza kubatsira kwakakosha mukiriniki, handiti? 

Dr. Rajeev Kumar: Zvechokwadi. 

Dr. Sarah Camargos: Saka, Dr. Rajeev, ndatenda. Tinotenda nguva yenyu uye kuda kwenyu kutora chikamu mupodcast, uye tinotarisira kuona kuti tsvakiridzo iyi ichachinja sei uye ichabatsira sei mukurapwa kwechirwere cheHuntington mune ramangwana. 

Dr. Rajeev Kumar: Ndinokutendai nemukana uyu. 

Dr. Sarah Camargos: Ndatenda. [00:23:00]