Inyandiko
Methylene blue n'indwara ya Alzheimer: gusobanukirwa amagerageza

Iyo ushakishije methylene blue n'indwara ya Alzheimer, ubona inkuru ebyiri icyarimwe. Imwe ivuga ko irangi ry'ubururu rimaze ikinyejana rigabanya umuvuduko wo gutakaza ubushobozi bwo kwibuka. Indi ivuga ko amagerageza yakurikiyeho atageze ku ntego. Izo nkuru zombi zishingira ku nyandiko z'ubushakashatsi zibaho koko. Urujijo ruterwa no gufata ibinyabutabire bitandukanye nk'aho ari umuti umwe.
Si umuti umwe. Igerageza rya mbere ryakoresheje methylthioninium chloride yakorewe okisidasiyo, cya kinyabutabire cy'ubururu gisanzwe kizwi. Buri gerageza rya Alzheimer ryakurikiyeho ryakoresheje ubwoko bwagabanyirijwe okisidasiyo kandi bugahabwa uburyo bwo kuguma butahindutse, ari bwo leuco-methylthioninium, ubu bwitwa hydromethylthionine mesylate (HMTM). Ingano z'umuti, uko winjira mu mubiri, ndetse n'amatsinda yo kugereranyaho biratandukanye muri izo gahunda zombi. Iyo utandukanyije ibyo binyabutabire, ibyavuye mu magerageza birushaho kumvikana, kandi ntibishyigikira kubikoresha nk'inyunganiramirire.
Ibinyabutabire bibiri
Methylene blue iri mu icupa akenshi iba ari methylthioninium chloride, mu magambo ahinnye MTC. Igice cyayo gikora ni iyoni ya methylthioninium yakorewe okisidasiyo, MT+, molekile ifite umuriro w'amashanyarazi n'ibara ry'ubururu bukomeye. Uwo muriro uteza ikibazo mu mara. Kugira ngo MT+ inyure neza mu rukuta rw'amara, igomba kubanza kugabanyirizwa okisidasiyo igahinduka ubwoko bwa leuco butagira umuriro w'amashanyarazi cyangwa ibara. Iyo ntambwe yo kugabanya okisidasiyo ntigenda kimwe buri gihe, kandi ku ngano nyinshi z'umuti, gushonga no kwinjira mu mubiri kwa MTC bigira imipaka iterwa n'ingano yafashwe. Iyi ni imwe mu mpamvu gahunda ya mbere ya Alzheimer yahuye n'ibibazo by'imiterere umuti utegurwamo.
Umuti wakurikiyeho wirinda iyo ntambwe. LMTM, izwi kandi ku kode TRx0237 kandi ubu ikunze kwitwa HMTM, itanga molekile yagabanyirijwe okisidasiyo mu buryo butaziguye, nk'umunyu wa mesylate ufite imiterere ya kristalo idahinduka. Methylthioninium yagabanyirijwe okisidasiyo itari mu buryo bw'umunyu yongera gukorerwa okisidasiyo igasubira ku ibara ry'ubururu mu minota mike iyo ihuye n'umwuka. Bityo, imiterere y'umunyu ni yo ituma iba umuti ushobora kubikwa, aho kuba ikintu gishishikaje gusa muri laboratwari. Muri make: MTC ni ikinyabutabire cy'ubururu cyakorewe okisidasiyo gihinduka umuti ukora mu mubiri, ariko cyinjira mu mubiri ku buryo butangana; LMTM/HMTM yo ni ubwoko bwagabanyirijwe okisidasiyo kandi bugakomezwa kugira ngo ingano igera mu mubiri ishobore guteganywa. Ibyemezo ku bushobozi bwa kimwe ntibishobora kwitirirwa ikindi, kandi nta na kimwe gishobora kwitirirwa ibisukika by'irangi bigurwa hatabayeho urwandiko rwa muganga. Ni ngombwa gusobanukirwa ubutabire bw'ubwo bwoko bwakorewe okisidasiyo n'ubwagabanyirijwe okisidasiyo mbere yo gusoma umutwe w'inkuru iyo ari yo yose ivuga ku igerageza.
Uburyo umuti ukora buri kugeragezwa na bwo bufite intego nto kurusha uko ibitangazamakuru bibigaragaza. Gahunda yibanda ku kwikusanya kwa tau, ni ukuvuga kwibumbira hamwe kwa poroteyine ya tau igakora udutsi n'urusobe rwizingiye imbere mu ngirabuzimafatizo z'imyakura, aho kwibanda ku birundo bya amyloid. Ibyo bituma iba inzira itandukanye n'iy'ubwirinzi bw'umubiri bukozwe nk'imiti irwanya amyloid. Iri kandi hamwe n'ubushakashatsi butarakorerwa ku bantu ku nzira zo gukuraho amyloid ndetse n'isesengura ryagutse ry'ibitekerezo ku mikorere ya mitokondiriya no kurinda ingirabuzimafatizo z'imyakura, bitagomba kwitiranywa n'ibimenyetso byemejwe mu magerageza ya kliniki.
Ikinyabutabire cyakoreshejwe muri buri gerageza
Iyi ni imbonerahamwe ukwiye kubika kugira ngo uzayisubireho. Buri murongo ugaragaza ikinyabutabire nyirizina, ingano z'umuti, ibipimo by'ibisubizo n'ikiranga igerageza, kuko ari muri ayo makuru incamake nyinshi zikora amakosa.
| Igerageza (ikinyabutabire) | Ingano z'umuti zageragejwe | Ikiranga igerageza | Ibipimo by'ibanze by'ibisubizo | Igisubizo cyo kugabanya abitabiriye mu matsinda ku buryo bwa tombola |
|---|---|---|---|---|
| Rember, icyiciro cya 2 (MTC, methylene blue yakorewe okisidasiyo) | 69, 138, 228 mg/day bingana na MT ugereranyije na placebo, ibyumweru 24 | NCT00515333 | ADAS-cog ku byumweru 24; ADCS-CGIC, MMSE, umuvuduko w'amaraso upimwa na SPECT nk'ibipimo by'inyongera | Muri rusange, nta mpinduka zagaragaye zijyanye no kongera ingano y'umuti. Itsinda rito ry'abafite indwara igeze ku rwego ruringaniye bafataga 138 mg/day ryagize iterambere ry'amanota 5.4 kuri ADAS-cog ugereranyije na placebo (p yakosowe = 0.047); abafite indwara yoroheje bafataga placebo ntibigeze basubira inyuma cyane, bityo kugereranya ntibyashobotse; ingano yo hejuru yagize ibibazo byo kwinjira mu mubiri |
| TRx237-015, icyiciro cya 3 (LMTM) | 150, 250 mg/day ugereranyije n'umuti ukora wo kugereranyaho wa 8 mg/day, ibyumweru 65 | NCT01689246 | Impinduka kuri ADAS-Cog na ADCS-ADL, byombi ari ibipimo by'ibanze, kugeza ku cyumweru cya 65 | Nta ntsinzi. Ingano nyinshi z'umuti nta nyungu ifatika zagize kurusha 8 mg/day yo kugereranyaho kuri buri gipimo |
| TRx237-005, icyiciro cya 3 (LMTM) | 200 mg/day ugereranyije n'umuti ukora wo kugereranyaho wa 8 mg/day, ibyumweru 78 | NCT01689233 | ADAS-cog11 na ADCS-ADL23, byombi ari ibipimo by'ibanze, ku byumweru 78 | Nta ntsinzi hakurikijwe uko amatsinda yagenwe ku buryo bwa tombola (gusubira inyuma kw'amanota +6.41 ugereranyije na +6.27 kuri ADAS-cog; ubushobozi bwo gukora ibikorwa bwari busa). Inyungu yagaragaye gusa mu isesengura ry'amatsinda mato yakoresheje uwo muti wonyine, atagenwe ku buryo bwa tombola |
| Lucidity, icyiciro cya 3 (gahunda ya HMTM 16 mg/day) | 16 mg/day, 8 mg/day, n'itsinda ryo kugereranyaho ryafashe MTC nkeya cyane, ibyumweru 52 hiyongereyeho gutangira umuti nyuma kugeza ku byumweru 104 | NCT03446001 | ADAS-cog11 na ADCS-ADL23, byombi ari ibipimo by'ibanze, ku byumweru 52 | Ingano z'umuti mu mubiri w'abari mu itsinda ryo kugereranyaho zageze ku rwego rukora rutari rwitezwe, bityo kugereranya umuti na placebo nta kibangamira ntibyashobotse; isesengura ryatangajwe ryibanda ku mpinduka uhereye ku bipimo byo mu ntangiriro, gutangira umuti nyuma no kugereranya ibimenyetso byo mu mubiri |
Inyandiko zuzuye: raporo ya Rember yo mu cyiciro cya 2, igerageza rya mbere rya LMTM ryo mu cyiciro cya 3, isesengura ry'itsinda ryitabiriye igerageza rya kabiri ryo mu cyiciro cya 3, isesengura rishya ry'isano hagati y'ingano y'umuti mu mubiri n'igisubizo, n'inyandiko ku miterere y'igerageza rya Lucidity.
Gusoma buri gisubizo nk'uko abateguye amagerageza babigenza
Banza urebe Rember. Yari ifite placebo nyayo, ibyo bikaba byiza, ariko irangi ry'ubururu rituma guhisha uwafashe umuti n'uwafashe placebo bigorana. Guhinduka kw'ibara ry'inkari n'umwanda bishobora kugaragaza uwafashe umuti ukora, kandi abashakashatsi bemeye ko itsinda rya placebo ritagaragazaga icyo kimenyetso. Batandukanyije abapimaga umutekano w'umuti n'abapimaga ubushobozi bwawo, kandi bagaragaza amakuru y'amashusho y'ibizamini nk'ayashyigikira ibisubizo. Nyamara, ibyago byo kumenya itsinda umuntu arimo biracyahari. Wongeraho ko ikimenyetso cy'inyungu cyagaragaye mu itsinda rito gusa n'uko ingano yo hejuru itageze ku ntego, umwanzuro utabogamye ni uko ibisubizo bishishikaje ariko bidakomeye. Ni yo mpamvu gahunda yimukiye ku kinyabutabire gishya aho gukora igerageza rinini kurushaho rya MTC.
Amagerageza abiri ya LMTM yo mu cyiciro cya 3 yakemuye ikibazo cyo guhisha amatsinda mu bundi buryo, ariko ateza ikibazo gishya. Kugira ngo inkari z'abari mu itsinda ryo kugereranyaho zikomeze kugira ibara ritandukanye, amagerageza yombi yabahaye 8 mg/day za LMTM nyayo. Niba 8 mg/day na zo zikora, kugereranya ingano nyinshi n'itsinda ryo kugereranyaho biba ari ukugereranya imiti ibiri. Bityo, kutabona itandukaniro ntibishobora gutandukanya "yombi irakora" na "nta n'umwe ukora." Isesengura ryakurikiyeho ry'abakoresheje uwo muti wonyine n'iry'ingano zawo mu maraso rishyigikira ko ingano nto na zo zakoraga koko, kandi inyandiko z'isesengura ku gusaza ziganira kuri iki kibazo cyo guhuza ubushakashatsi n'ikoreshwa mu buvuzi. Ariko iryo sesengura ntirikomeza kugendera ku kugabanya amatsinda ku buryo bwa tombola. Kuba umurwayi yarafashe LMTM yonyine cyangwa akayifatana n'imiti isanzwe ya Alzheimer byaterwaga n'imiti yari yarandikiwe mbere, si tombola. Bityo, itandukaniro mu miti yandikiwe n'ubuzima bwo mu ntangiriro bishobora gusobanura igice cy'itandukaniro ryabonetse. Ubushakashatsi ku isano hagati y'ingano y'umuti mu mubiri n'igisubizo bukomeza ibisobanuro bishingiye ku mikorere y'umubiri, ariko ntibutanga uko kugereranya na placebo idakora kwabuzemo.
Lucidity yongeye gukurikiza iyo nzira, ikoresheje ingano nto. Itsinda ryo kugereranyaho ryafataga ingano nto za MTC kabiri mu cyumweru, zigamije gusa guha inkari ibara. Nyamara, benshi mu bari muri iryo tsinda bageze ku ngano z'umuti mu mubiri zishobora kugira icyo zikora. Umuterankunga yavuze yeruye ko kugereranya na placebo idakora, nk'uko byari byateganyijwe, bitashoboraga gukorwa. Raporo zakurikiyeho zishimangira itandukaniro ry'ibimenyetso byo mu mubiri n'iry'abatangiye umuti nyuma. Ibyo bitanga amakuru ku mikorere y'indwara mu mubiri, ariko ntibihwanye no gutsinda placebo mu igerageza ryateganyijwe mbere. Mu gihe cya 2024 kugeza muri 2025, icyo kinyabutabire cyari kigikorerwaho ubushakashatsi; ubusabe bwo kwemererwa kugikoresha bwari bwaratanzwe mu Bwongereza, naho inyandiko yemeza ibimenyetso byo mu mubiri yari ikiri mu isuzuma ry'abandi bahanga.
Icyo ibi bivuze ku musomyi utekereza gukoresha methylene blue
Hari ingingo eshatu zifatika zikurikira.
Icya mbere, imiti yo mu magerageza si inyunganiramirire. HMTM ni umunyu w'umuti wasukuwe, ufite imiterere imwe gusa, utangwa ku ngano ya 8 kugeza kuri 16 mg/day muri gahunda iriho ubu. Methylene blue yo mu icupa akenshi ni chloride yakorewe okisidasiyo, ifite ubuziranenge butandukanye, ipimwa hakoreshejwe igitonyangamuti, kandi uburyo yinjira mu mubiri n'imyanda irimo biratandukanye. Kuba ingano nto za HMTM zarashoboye kwihanganirwa mu magerageza ntacyo bivuga ku kwifatira ibisukika by'irangi igihe kirekire.
Icya kabiri, ibimenyetso by'ibibazo by'umutekano byabonetse igihe hakoreshwaga ingano nyinshi bikwiye kwitabwaho, nubwo ingano zikoreshwa ubu ari nto. Muri gahunda nini y'icyiciro cya 3, impiswi yageze kuri hafi umwe muri bane mu barwayi bafataga ingano nyinshi, kandi isesemi, kuruka no kumva inkari zikubanye na byo byariyongereye ku buryo bugaragara. Abantu bafite ibura rya G6PD ntibemerewe kwitabira kuko imiti ya methylthioninium ishobora gutera isenyuka ry'insoro zitukura muri iryo tsinda. Imikoranire n'imiti ivura agahinda gakabije ikorera kuri serotonine ni ikintu gifatika mu mikorere y'imiti, kuko methylene blue ari umuti ukomeye uhagarika MAO-A by'agateganyo. Ibyo ni ko biri nubwo amagerageza ya Alzheimer yanditse gusa ibimenyetso byamaraga igihe gito ku bantu bake bakoreshaga SSRI, aho kwemeza sindorome ya serotonine. Umuntu wese ufatanya iyo miti akeneye gukurikiranwa n'umuganga; iyi ngingo isobanurwa birambuye mu nyandiko y'ubuyobozi ku mutekano n'imikoranire y'imiti.
Icya gatatu, ibyo witeze bikwiye kujyana n'urwego ibimenyetso bigezeho. Ikimenyetso cy'inyungu mu itsinda rito, hiyongereyeho kugereranya kabiri amatsinda yagenwe ku buryo bwa tombola kutageze ku ntego, ndetse n'itsinda ryo kugereranyaho rifite ibibangamira gusobanura ibisubizo, ni igitekerezo cyo gukomeza gukoraho ubushakashatsi, si icyifuzo cyo kuvura. Imiryango isuzuma amahitamo izabona amakuru afatika kurushaho mu gusobanukirwa uko ibyemezo byo kwita ku barwaye Alzheimer bifatwa koko, kuruta muri gahunda iyo ari yo yose yo gukoresha irangi ikwirakwizwa kuri interineti.
Umwanzuro ushobora kuvugwa mu nteruro imwe. Methylene blue yakorewe okisidasiyo yatanze ikimenyetso kimwe cy'inyungu kidakomeye mu cyiciro cya 2, gifite imbogamizi zo guhisha amatsinda no kwinjira mu mubiri; iyayisimbuye yagabanyirijwe okisidasiyo ntiyatsinze mu kugereranya kabiri ingano z'umuti mu matsinda yagenwe ku buryo bwa tombola; kandi gahunda y'ingano nto ntiratanga intsinzi igaragara mu igerageza rigereranya na placebo nta kibangamira ibisubizo. Ibyo bishobora guhinduka bitewe n'inyandiko zizatangazwa cyangwa isuzuma ry'inzego zibishinzwe. Kugeza bihindutse, gukoresha methylene blue ku ndwara ya Alzheimer biguma mu cyiciro cy'ubushakashatsi bukomeye butarahinduka ubuvuzi.