Maƙala
Methylene blue da cutar Alzheimer: fahimtar gwaje-gwajen

Idan ka bincika methylene blue da cutar Alzheimer, za ka sami labarai biyu a lokaci guda. Ɗaya ya ce wani rinin shuɗi da ya kai shekaru ɗari ya rage saurin lalacewar ƙwaƙwalwar ajiya. Ɗayan kuma ya ce gwaje-gwajen da suka biyo baya sun gaza. Duk labaran biyu suna ambaton takardun bincike na gaske. Ruɗanin ya samo asali ne daga ɗaukar sinadarai daban-daban a matsayin magani guda ɗaya.
Ba magani guda ɗaya ba ne. Gwajin farko ya gwada methylthioninium chloride da aka yi wa oxidation, wato sanannen sinadarin shuɗi. Kowane gwajin Alzheimer da ya biyo baya ya gwada nau'in da aka rage ta hanyar sinadarai kuma aka tabbatar da dawwamarsa, leuco-methylthioninium, wanda yanzu ake kira hydromethylthionine mesylate (HMTM). Adadin magani, shigar sa cikin jiki, har ma da rukunonin kwatanci sun bambanta tsakanin shirye-shiryen biyu. Da zarar an ware sinadaran daga juna, tarihin gwaje-gwajen zai zama a sarari, kuma ba ya nuna goyon bayan amfani da ƙarin abinci.
Sinadaran biyu
Methylene blue da ke cikin kwalba yawanci methylthioninium chloride ne, wanda ake taƙaitawa da MTC. Sashensa mai aiki shi ne ion na methylthioninium da aka yi wa oxidation, MT+, wani ƙwayar sinadari mai cajin lantarki da launin shuɗi mai ƙarfi. Cajin lantarki yana haifar da matsala a hanji. Don MT+ ya ratsa bangon hanji yadda ya kamata, dole ne a fara rage shi zuwa nau'in leuco marar cajin lantarki kuma marar launi. Wannan matakin ragewar ba ya faruwa daidai a kowane yanayi, kuma idan adadin magani ya yi yawa, adadin magani yana takaita narkewar MTC da shigarsa cikin jiki. Wannan na ɗaya daga cikin dalilan da shirin Alzheimer na farko ya samu matsalar tsarin haɗa maganin.
Maganin da ya biyo baya yana kauce wa wannan mataki. LMTM, wanda kuma ke da lambar TRx0237 kuma yanzu aka fi kira HMTM, yana samar da ƙwayar sinadarin da aka rage kai tsaye a matsayin gishirin mesylate mai ƙirar kristal kuma mai dawwama. Methylthioninium da aka rage, idan ba ya cikin gishiri, yana sake komawa shuɗi ta oxidation cikin mintuna kaɗan a iska. Saboda haka, nau'in gishirin ne ke sa ya zama maganin da za a iya adanawa, maimakon wani abin ban sha'awa na dakin gwaje-gwaje kawai. A taƙaice: MTC shi ne shuɗin sinadarin da aka yi wa oxidation wanda jiki ke sauyawa zuwa magani mai aiki, kuma shigarsa cikin jiki ba ta daidaita; LMTM/HMTM kuwa shi ne nau'in da aka rage kuma aka tabbatar da dawwamarsa, wanda aka tsara domin a iya hasashen yawan maganin da jiki zai samu. Da'awar ingancin ɗaya ba ta shafi ɗayan kai tsaye, kuma da'awar kowane ɗayansu ba ta shafi ruwan rini da ake sayarwa ba tare da takardar likita ba. Ya dace a fahimci kimiyyar sinadarai da ke bayan nau'in da aka yi wa oxidation da nau'in da aka rage kafin karanta kanun labarin kowane gwaji.
Hanyar aikin da ake gwadawa kuma ta fi abin da rahotannin jaridu ke nunawa takamaimai. Shirin yana nufin taruwar tau, wato dunƙulewar furotin tau zuwa zaruruwa da sarƙaƙƙiya a cikin ƙwayoyin jijiyoyi, maimakon tarin amyloid. Wannan ya sa hanyar ta bambanta da ta ƙwayoyin kariya masu yaƙi da amyloid. Haka kuma, tana tare da wasu ayyukan daban na binciken kafin gwaji a mutane kan hanyoyin kawar da amyloid da kuma bita mai faɗi kan hasashen da ya shafi mitochondria da kare ƙwayoyin jijiyoyi, waɗanda bai kamata a ɗauka a matsayin hujjar gwajin asibiti ba.
Kowane sinadari da gwajinsa
Wannan shi ne jadawalin da ya kamata a adana domin komawa gare shi. Kowane layi ya bayyana takamaiman sinadari, adadin magani, ma'aunan sakamako, da lambar gwaji, domin waɗannan bayanai ne yawancin taƙaitattun rahotanni suke kuskure a kai.
| Gwaji (sinadari) | Adadin maganin da aka gwada | Lambar gwaji | Manyan ma'aunan sakamako | Sakamakon gwajin da aka raba mahalarta ta bazuwar zaɓi |
|---|---|---|---|---|
| Rember, mataki na 2 (MTC, methylene blue da aka yi wa oxidation) | 69, 138, 228 mg/day daidai da MT idan aka kwatanta da placebo, makonni 24 | NCT00515333 | ADAS-cog a makonni 24; ADCS-CGIC, MMSE, kwararar jini ta SPECT a matsayin ma'aunan sakamako na biyu | Babu alaƙa ta gaba ɗaya tsakanin adadin magani da martani. Rukunin masu cutar matsakaici da suka karɓi 138 mg/day ya samu ci gaban maki 5.4 na ADAS-cog idan aka kwatanta da placebo (p da aka daidaita = 0.047); masu cutar mai sauƙi da suka karɓi placebo kusan ba su samu tabarbarewa ba, don haka ba a iya yin kwatanci ba; adadin mafi girma ya samu matsalar shiga cikin jiki |
| TRx237-015, mataki na 3 (LMTM) | 150, 250 mg/day idan aka kwatanta da 8 mg/day na magani mai aiki a rukunin kwatanci, makonni 65 | NCT01689246 | Sauyin ADAS-Cog da ADCS-ADL zuwa mako na 65 a matsayin manyan ma'aunan sakamako biyu | Bai nuna nasara ba. Adadin magani mai yawa kusan bai fi 8 mg/day na rukunin kwatanci ba a kowane ɗayan ma'aunan biyu |
| TRx237-005, mataki na 3 (LMTM) | 200 mg/day idan aka kwatanta da 8 mg/day na magani mai aiki a rukunin kwatanci, makonni 78 | NCT01689233 | ADAS-cog11 da ADCS-ADL23 a makonni 78 a matsayin manyan ma'aunan sakamako biyu | Bai nuna nasara ba bisa rabon mahalarta na bazuwar zaɓi (tabarbarewar maki +6.41 idan aka kwatanta da +6.27 na ADAS-cog; ikon gudanar da ayyuka ya yi kama). An ga fa'ida ne kawai a nazarin ƙananan rukunonin masu amfani da magani guda ɗaya waɗanda ba a raba su ta bazuwar zaɓi ba |
| Lucidity, mataki na 3 (shirin HMTM 16 mg/day) | 16 mg/day, 8 mg/day, da MTC mai matuƙar ƙarancin adadi a rukunin kwatanci, makonni 52 tare da farawa a jinkire har zuwa makonni 104 | NCT03446001 | ADAS-cog11 da ADCS-ADL23 a makonni 52 a matsayin manyan ma'aunan sakamako biyu | Magani a rukunin kwatanci ya kai matakan da za su iya yin aiki ba zato ba tsammani, don haka ba a iya yin kwatanci tsantsa tsakanin magani da placebo ba; nazarin da aka ruwaito ya fi dogaro da sauyi daga matakin farko, farawa a jinkire, da kwatancen alamomin halittu |
Cikakkun wallafe-wallafe: rahoton Rember na mataki na 2, gwajin LMTM na farko na mataki na 3, nazarin rukunin mahalarta na gwaji na biyu na mataki na 3, sake nazarin alaƙar matakin magani a jiki da martani, da takardar tsarin gwajin Lucidity.
Fahimtar kowane sakamako kamar yadda masu tsara gwajin za su yi
A fara da Rember. Yana da placebo na gaske marar magani mai aiki, wanda abu ne mai kyau, amma rinin shuɗi yana sa ɓoye wanda ke karɓar magani ya yi wuya. Sauyin launin fitsari da bayan gida zai iya bayyana wanda yake shan magani mai aiki, kuma masu binciken sun amince cewa rukunin placebo bai nuna wannan alamar ba. Sun ware masu tantance aminci daga masu tantance ingancin magani, kuma sun yi nuni da bayanan hotunan cikin jiki don ƙarfafa sakamakonsu. Duk da haka, akwai sauran haɗarin gano wanda ke cikin kowane rukuni. Idan aka haɗa wannan da alamar fa'ida da aka gani a ƙaramin rukuni kawai, da rashin nasarar adadin magani mafi girma, hukuncin gaskiya shi ne sakamakon yana da ban sha'awa amma ba shi da ƙarfi. Shi ya sa shirin ya koma ga sabon sinadari maimakon gudanar da babban gwajin MTC.
Gwaje-gwajen LMTM biyu na mataki na 3 sun magance matsalar ɓoye rukunin magani ta wata hanya, amma suka haifar da sabuwar matsala. Don fitsarin masu rukunin kwatanci ya ci gaba da samun launi, duk gwaje-gwajen biyu sun ba su 8 mg/day na LMTM na gaske. Idan 8 mg/day kansa yana aiki, to kwatanta adadi mai yawa da rukunin kwatanci yana nufin kwatanta jiyya biyu ne. Sakamakon da bai nuna bambanci ba ba zai iya bambanta tsakanin “dukkansu suna aiki” da “babu wanda yake aiki” ba. Nazarin amfani da magani guda ɗaya da na matakan magani a jini da aka yi daga baya suna nuna cewa ƙaramin adadin yana aiki da gaske, kuma wallafe-wallafen bita kan tsufa suna tattauna wannan matsalar fassara sakamakon bincike zuwa amfani da magani. Amma waɗannan nazarce-nazarcen ba sa kiyaye rabon mahalarta na bazuwar zaɓi. Ko mara lafiya ya ɗauki LMTM shi kaɗai ko tare da magungunan Alzheimer da aka saba amfani da su ya dogara ne da maganin da aka riga aka rubuta masa, ba da jefa tsabar kuɗi ba. Saboda haka, bambancin rubuta magunguna da yanayin lafiyar mahalarta tun kafin gwaji zai iya bayyana wani ɓangare na bambancin sakamakon. Binciken alaƙar matakin magani a jiki da martani yana ƙarfafa bayanin abin da ke faruwa a jiki, amma ba ya samar da kwatancin da ya ɓace da placebo marar wani aiki.
Lucidity ya sake bin wannan tsari a ƙananan adadin magani. Rukunin kwatanci ya karɓi ƙananan adadin MTC sau biyu a mako domin sauya launin fitsari kawai, amma magani ya taru a jikin mahalarta da yawa a wannan rukuni har ya kai matakan da za su iya yin aiki. Mai ɗaukar nauyin gwajin ya bayyana a sarari cewa ba a iya yin kwatancin da aka yi niyya da placebo marar aiki ba. Rahotannin da suka biyo baya sun fi jaddada kwatancen alamomin halittu da farawa a jinkire. Waɗannan suna ba da bayani game da abin da ke faruwa a jiki yayin cutar, amma ba daidai suke da nasarar da aka nuna a gwajin da aka tsara tun farko domin kwatanta magani da placebo ba. A tsakanin 2024 zuwa 2025, sinadarin ya ci gaba da kasancewa a matakin bincike, an gabatar da neman izini a UK, kuma takardar tabbatarwa ta alamomin halittu tana ci gaba da bin tsarin bitar masana.
Abin da wannan yake nufi ga mai karatu da ke tunanin amfani da methylene blue
Akwai muhimman abubuwa uku na amfani da za a fahimta.
Na farko, magungunan gwajin ba su ne ƙarin abincin ba. HMTM gishirin magani ne tsarkakakke mai nau'i guda ɗaya, wanda ake ba da shi a adadin 8 zuwa 16 mg/day a shirin yanzu. Methylene blue na kwalba kuwa yawanci nau'in chloride ne da aka yi wa oxidation, mai bambancin tsabta, wanda ake auna shi da na'urar ɗigawa, kuma shigarsa cikin jiki da irin ƙazantun da ke cikinsa sun bambanta. Yadda mahalarta gwaji suka jure ƙananan adadin HMTM ba ya nuna komai game da shan ruwan rini da kai na dogon lokaci.
Na biyu, ya kamata a ɗauki alamomin haɗarin da aka gani a lokacin amfani da manyan adadin magani da muhimmanci, ko da yake adadin da ake amfani da shi yanzu ya yi ƙasa. A babban shirin mataki na 3, gudawa ta shafi kusan ɗaya cikin kowane marasa lafiya huɗu masu karɓar adadi mai yawa, yayin da tashin zuciya, amai, da buƙatar yin fitsari cikin gaggawa su ma suka ƙaru a sarari. An ware mutanen da ke da ƙarancin G6PD daga gwajin saboda magungunan methylthioninium na iya jawo rushewar jajayen ƙwayoyin jini a wannan rukuni. Hulɗarsa da magungunan rage baƙin ciki masu shafar serotonin tana da tushe na gaske a ilimin aikin magunguna, domin methylene blue mai hana aikin MAO-A ne mai ƙarfi wanda tasirinsa kan enzyme ɗin zai iya juyawa. Duk da haka, gwaje-gwajen Alzheimer sun rubuta alamomi na ɗan lokaci ne kawai a wasu tsirarun masu amfani da SSRI, maimakon tabbatar da cutar yawan serotonin. Duk wanda ke haɗa waɗannan magunguna yana buƙatar kulawar ƙwararren mai kula da lafiya, batun da aka yi bayani dalla-dalla a jagorar aminci da hulɗar magunguna.
Na uku, a daidaita tsammani da matakin shaidar da ake da ita. Alamar fa'ida a ƙaramin rukuni, tare da kwatance biyu na bazuwar zaɓi da ba su nuna nasara ba, da rukunin kwatanci da wasu abubuwa suka rikita fassarar sakamakonsa, suna samar da hasashen bincike ne, ba shawarar jiyya ba. Iyalai masu tantance zaɓuɓɓuka za su sami bayanai mafi amfani a yadda ake yanke shawarwarin kula da Alzheimer a zahiri, maimakon kowace hanyar amfani da rini da ke yawo a intanet.
Ana iya bayyana ƙarshe cikin jimla ɗaya mai sauƙi. Methylene blue da aka yi wa oxidation ya nuna alamar fa'ida guda ɗaya marar ƙarfi a mataki na 2, tare da matsalolin ɓoye rukunin magani da shigar maganin cikin jiki; nau'in da aka rage wanda ya gaje shi bai yi nasara a kwatancen adadin magani biyu da aka raba mahalarta ta bazuwar zaɓi ba; kuma shirin ƙaramin adadin magani bai riga ya nuna nasara tsantsa a gwajin da ke da placebo a matsayin kwatanci ba. Wannan na iya sauyawa da wallafe-wallafen gaba ko bitar hukumomin kula da magunguna. Har sai hakan ya faru, methylene blue don cutar Alzheimer yana cikin rukunin binciken kimiyya mai muhimmanci wanda bai riga ya zama magani ba.