Chinyorwa
Methylene blue nechirwere cheAlzheimer: kududzira miedzo
Tsvaga nezve methylene blue nechirwere cheAlzheimer, uye unowana nyaya mbiri panguva imwe chete. Imwe inoti dhayi rebhuruu rine zana remakore richishandiswa rakanonotsa kurasikirwa nendangariro. Imwe inoti miedzo yakatevera haina kubudirira. Nyaya dzose dziri mbiri dzinotaura mapepa etsvakurudzo chaiwo. Kuvhiringidzika kunobva pakutora makomponi akasiyana semushonga mumwe chete.
Haasi mushonga mumwe chete. Muedzo wekutanga wakaedza methylthioninium chloride iri muchimiro cheoxidation, iro komponi rebhuruu rinozivikanwa. Muedzo wega wega weAlzheimer wakazotevera wakaedza chimiro chakaderedzwa uye chakagadzikiswa, leuco-methylthioninium, chave kunzi hydromethylthionine mesylate (HMTM). Madhosi, kutorwa nemuviri, uye kunyange mapoka ekuenzanisa zvakasiyana pakati pezvirongwa zviviri izvi. Kana ukachengeta makomponi aya akasiyana, zvinyorwa zvemiedzo zvinonzwisisika, uye hazvinongedzi kukushandisa zvekuwedzera pakudya.
Makomponi maviri
Methylene blue iri mubhodhoro inowanzova methylthioninium chloride, yakapfupikiswa kuti MTC. Chikamu chayo chinoshanda iion yemethylthioninium iri muchimiro cheoxidation, MT+, morekuru rine chaji yemagetsi uye rine ruvara rwebhuruu rwakadzama. Chaji iyi idambudziko chairo muura. Kuti MT+ iyambuke madziro eura zvakanaka, inofanira kutanga yashandurwa nekuderedzwa kuita chimiro cheleuco chisina chaji uye chisina ruvara. Nhanho iyi yekuderedzwa haifambi zvakafanana nguva dzose, uye pamadhosi akakwirira kunyunguduka nekutorwa kweMTC nemuviri zvinoganhurirwa nekukura kwedhosi, chinova chimwe chezvikonzero zvakaita kuti chirongwa chekutanga cheAlzheimer chisangane nezvinetso pakugadzirwa kwemushonga.
Mushonga wakatevera unonzvenga nhanho iyoyo. LMTM, inewo kodhi TRx0237 uye yava kunyanya kunzi HMTM, inopa morekuru rakaderedzwa zvakananga semunyu wemakristaro wemesylate wakagadzikana. Methylthioninium yakaderedzwa isiri mumunyu inodzokera kubhuruu kuburikidza neoxidation mukati memaminitsi kana iri mumhepo, saka chimiro chemunyu ndicho chinoita kuti ive mushonga unogona kuchengetwa pane kungova chinhu chinonakidza murabhoritari. Muchidimbu: MTC ikomponi rebhuruu riri muchimiro cheoxidation rinofanira kutanga rashandurwa mumuviri kuti rishande, uye kutorwa kwaro nemuviri hakufanani nguva dzose; LMTM/HMTM ndiyo chimiro chakaderedzwa uye chakagadzikiswa, chakagadzirirwa kuti huwandu hunosvika mumuviri hufanotaurika. Zvinotaurwa nezvekushanda kweimwe hazvishandi kune imwe, uye hapana pazviri zvinoshandawo kumvura yedhayi inotengwa pasina tsamba yachiremba. Zvakakodzera kunzwisisa kemisitiri iri shure kwezvimiro zveoxidation nezvakaderedzwa usati waverenga chero musoro wenhau wemuedzo.
Nzira yekushanda iri kuedzwa yakamanikawo kupfuura zvinoratidzwa nenhau. Chirongwa ichi chakanangana nekuungana kwetau, kureva kuungana kweprotein yetau kuita tambo netambo dzakamonereka mukati memasero etsinga, kwete maplaque eamyloid. Izvi zvinoita kuti ive nzira yakasiyana neyekushandisa masoja ekudzivirira muviri anorwisa amyloid, uye iri pamwe chete netsvakurudzo yakasiyana isati yasvika kumiedzo muvanhu pamusoro penzira dzekubvisa amyloid pamwe neongororo dzakafara dzepfungwa dzine chekuita nemitochondria nekudzivirira masero etsinga, izvo zvisingafaniri kutorwa sehumbowo hunobva mumiedzo yevarwere.
Komponi rimwe nerimwe mumuedzo waro
Iyi ndiyo tafura yokuchengeta kuti ugozodzokera kwairi. Mutsetse wega wega unodoma komponi chaiyo, madhosi, zviyero zvemigumisiro, uye chiziviso chemuedzo, nokuti mashoko aya ndiwo anowanzokanganiswa mupfupiso zhinji.
| Muedzo (komponi) | Madhosi akaedzwa | Chiziviso chemuedzo | Zviyero zvikuru zvemigumisiro | Mugumisiro pakugoverwa nemukana |
|---|---|---|---|---|
| Rember, chikamu 2 (MTC, methylene blue iri muchimiro cheoxidation) | 69, 138, 228 mg/day zvakaenzana neMT zvichienzaniswa neplacebo, mavhiki 24 | NCT00515333 | ADAS-cog pamavhiki 24; ADCS-CGIC, MMSE, kuyerera kweropa kunoyerwa neSPECT sezviyero zvechipiri | Pakazara, pakanga pasina shanduko yaienderana nedhosi. Muboka diki revarwere vane chirwere chepakati nepakati, 138 mg/day yakavandudza ADAS-cog nemapoinzi 5.4 zvichienzaniswa neplacebo (p yakagadziridzwa = 0.047); varwere vane chirwere chisina kunyanya kukura havana kumbonyanya kudzikira pavakapiwa placebo, saka kuenzanisa kwakanga kusingakwanisiki; dhosi repamusoro raiva nezvinetso zvekutorwa nemuviri |
| TRx237-015, chikamu 3 (LMTM) | 150, 250 mg/day zvichienzaniswa ne8 mg/day muboka rekuenzanisa raipiwa mushonga unoshanda, mavhiki 65 | NCT01689246 | Shanduko yeADAS-Cog neADCS-ADL kusvika pavhiki 65, zvose zviri zviyero zvikuru | Hazvina kubudirira. Madhosi akakwirira haana kunyanya kukunda 8 mg/day yeboka rekuenzanisa pachiyero chipi nechipi |
| TRx237-005, chikamu 3 (LMTM) | 200 mg/day zvichienzaniswa ne8 mg/day muboka rekuenzanisa raipiwa mushonga unoshanda, mavhiki 78 | NCT01689233 | ADAS-cog11 neADCS-ADL23 pamavhiki 78, zvose zviri zviyero zvikuru | Hazvina kubudirira maererano nekugoverwa nemukana (+6.41 zvichienzaniswa ne+6.27 mapoinzi eADAS-cog ekudzikira; kugona kuita mabasa kwakafanana). Kubatsira kwakaonekwa chete muongororo dzemaboka madiki aishandisa mushonga uyu woga, asina kugoverwa nemukana |
| Lucidity, chikamu 3 (chirongwa cheHMTM 16 mg/day) | 16 mg/day, 8 mg/day, neboka rekuenzanisa raipiwa MTC shomanana, mavhiki 52 pamwe nekutanga mushonga gare gare kusvika pamavhiki 104 | NCT03446001 | ADAS-cog11 neADCS-ADL23 pamavhiki 52, zvose zviri zviyero zvikuru | Huwandu hwemushonga muboka rekuenzanisa hwakasvika pamazinga anoshanda zvisingatarisirwi, saka kuenzanisa mushonga neplacebo pasina chinovhiringidza kwakanga kusingakwanisiki; ongororo dzakataurwa dzinonyanya kutsamira pashanduko kubva pakutanga, kutanga mushonga gare gare, uye kuenzanisa zviratidzo zvebiological |
Zvinyorwa zvakazara: mushumo weRember wechikamu 2, muedzo wekutanga weLMTM wechikamu 3, ongororo yeboka remuedzo wechipiri wechikamu 3, kuongororazve hukama pakati pehuwandu hwemushonga mumuviri nemhinduro yawo, uye pepa rinotsanangura magadzirirwo eLucidity.
Kuverenga mugumisiro wega wega semaonerwo aungaitwa nevakagadzira miedzo
Tanga wafunga nezveRember. Yaiva neplacebo chaiyo, izvo zvakanaka, asi dhayi rebhuruu rinoita kuti zviome kuvanzira vatori vechikamu nevaongorori kuti ndiani ari kupiwa mushonga unoshanda. Kuchinja kweruvara rweweti netsvina kunogona kuratidza kuti ndiani ari kutora mushonga unoshanda, uye vaongorori vakabvuma kuti boka replacebo rakanga risina chiratidzo ichocho. Vakaparadzanisa vaiongorora kuchengeteka nevaiongorora kushanda kwemushonga, uye vakashandisa mashoko ekuongorora nemifananidzo sechitsigiro, asi njodzi yekuti zvizivikanwe kuti ndiani ari muboka ripi ichiripo. Kana ukawedzera chiratidzo chakaonekwa muboka diki chete uye dhosi repamusoro risina kubudirira, mutongo wakatendeseka ndewekuti migumisiro iyi inonakidza asi haina kusimba. Ndokusaka chirongwa chakaenda kukomponi itsva pane kuita muedzo mukuru weMTC.
Miedzo miviri yeLMTM yechikamu 3 yakagadzirisa dambudziko rekuvanzwa kwemapoka neimwe nzira, ikabva yagadzira dambudziko idzva. Kuti weti irambe iine ruvara rwakachinja muboka rekuenzanisa, miedzo yose iri miviri yakapa vanhu veboka iroro 8 mg/day yeLMTM chaiyo. Kana 8 mg/day pachayo ichishanda, kuenzanisa dhosi rakakwirira neboka rekuenzanisa kunenge kuri kuenzanisa mishonga miviri inoshanda, uye mugumisiro usingaratidzi musiyano haugoni kusiyanisa kuti "zvose zviri zviviri zvinoshanda" kana kuti "hapana chinoshanda." Ongororo dzakazotevera dzevanhu vaishandisa mushonga uyu woga uye dzehuwandu hwemushonga muropa dzinotsigira pfungwa yokuti dhosi diki raishanda zvechokwadi, uye zvinyorwa zveongororo pamusoro pekukwegura zvinokurukura dambudziko iri rekushandura tsvakurudzo kuti ishandiswe mukurapa, asi ongororo idzodzo hadzichachengetedzi kugoverwa nemukana. Kuti murwere aitora LMTM yoga kana pamwe nemishonga yakajairika yeAlzheimer zvaibva pamishonga yaakanga atonyorerwa, kwete pakusarudzwa nemukana, saka kusiyana kwemishonga yakanyorerwa vanhu nehutano hwavo pakutanga kungatsanangura chikamu chemusiyano. Basa rekuongorora hukama pakati pehuwandu hwemushonga mumuviri nemhinduro yawo rinosimbisa tsananguro yebiological pasina kupa kuenzanisa kusipo neplacebo isingashandi.
Lucidity yakazodzokorora maitiro aya pamadhosi madiki. Boka rekuenzanisa raipiwa madhosi madiki eMTC kaviri pavhiki, aingovavarirwa kupa weti ruvara, asi vatori vechikamu vakawanda muboka iri vakaunganidza huwandu hwemushonga hwaigona kuva nesimba rekushanda mumuviri. Mutsigiri wemuedzo akataura pachena kuti kuenzanisa kwaivavarirwa neplacebo isingashandi kwakanga kusingakwanisiki. Mishumo yakatevera inosimbisa kuenzanisa kwezviratidzo zvebiological nekutanga mushonga gare gare, izvo zvinopa ruzivo nezvemashandiro echirwere asi hazvina kufanana nekubudirira pamberi peplacebo mumuedzo wakarongwa pachine nguva. Pakati pa2024 na2025 komponi iyi yakanga ichiri pasi pekutsvakurudzwa, chikumbiro chemvumo muUK chatumirwa uye pepa rekusimbisa zviratidzo zvebiological richiri kuongororwa nedzimwe nyanzvi.
Zvinorehwa neizvi kumuverengi ari kufunga kushandisa methylene blue
Pane pfungwa nhatu dzinoshanda dzinobva pane izvi.
Chekutanga, mishonga yemiedzo haisi chinhu chinotengeswa sechokuwedzera pakudya. HMTM munyu wemushonga wakacheneswa une chimiro chimwe chete, unopiwa pa8 kusvika ku16 mg/day muchirongwa chiripo. Methylene blue yemubhodhoro inowanzova chloride iri muchimiro cheoxidation, ine kuchena kunosiyana, inopimwa nechidonhedzo, uye ine kutorwa nemuviri nezvinhu zvinosvibisa zvakasiyana. Kushivirirwa kwemadhosi madiki eHMTM mumiedzo hakutauri chinhu pamusoro pekuzvipa mvura yedhayi kwenguva refu.
Chechipiri, zviratidzo zvenjodzi kubva panguva yaishandiswa madhosi akakwirira zvinofanira kukosheswa kunyange zvazvo madhosi aripo iye zvino ari madiki. Muchirongwa chikuru chechikamu 3, manyoka akabata angangoita mumwe pavarwere vana vaipiwa madhosi akakwirira, uye kusvotwa, kurutsa, nekukasira kuda kuita weti zvakawedzerawo zvakajeka. Vanhu vane kushomeka kweG6PD vakabviswa mumiedzo nokuti mishonga yemethylthioninium inogona kukonzera kuparara kwemasero matsvuku eropa muboka iroro. Kudyidzana nemishonga yekuora mwoyo inokanganisa serotonin chinhu chaicho chinobva pamashandiro emishonga, nokuti methylene blue imudzivisi ane simba weMAO-A ane kushanda kunodzoreka, kunyange zvazvo miedzo yeAlzheimer yakangonyora zviratidzo zvenguva pfupi muvanhu vashomanana vaishandisa maSSRI pane serotonin syndrome yakasimbiswa. Chero munhu anobatanidza mishonga iyi anoda kutarisirwa nenyanzvi yezvekurapa, pfungwa inotsanangurwa zvakadzama mugwaro rekuchengeteka nekudyidzana kwemishonga.
Chechitatu, tarisiro ngaifambirane nedanho rasvika humbowo. Chiratidzo chinobva muboka diki pamwe nekuenzanisa kuviri kwakaitwa nekugoverwa nemukana kusina kubudirira, pamwe neboka rekuenzanisa rine zvinhu zvinovhiringidza kududzirwa kwemigumisiro, ipfungwa yekutsvakurudza, kwete kurudziro yekurapa. Mhuri dziri kuyera sarudzo dzichawana ruzivo runobatsira pakuita zviri nani mukunzwisisa kuti sarudzo dzekuchengeta munhu ane Alzheimer dzinoitwa sei chaizvo, pane chero chirongwa chekushandisa dhayi chiri kutenderera paindaneti.
Mhedziso yacho iri nyore kutaura mumutsara mumwe chete. Methylene blue iri muchimiro cheoxidation yakaratidza chiratidzo chimwe chete chisina kusimba muchikamu 2, paine zvinofanira kungwarirwa nezvekuvanzwa kwemapoka nekutorwa nemuviri; komponi yakaderedzwa yakaitevera haina kubudirira mukuenzanisa madhosi kuviri kwakaitwa nekugoverwa nemukana; uye chirongwa chemadhosi madiki hachisati charatidza kubudirira kwakajeka mumuedzo unodzorwa neplacebo. Izvozvo zvinogona kuchinja nezvinyorwa zvichabuda mune ramangwana kana nekuongororwa nevakuru vanobvumidza mishonga. Kusvikira zvadaro, methylene blue yechirwere cheAlzheimer iri muboka resainzi yakakomba isati yava mushonga wekushandisa mukurapa.