Shin masu maganin JAK ne da aka kwatanta a matsayin maganin kwayoyi?
JAK (Janus kinase) masu hana shi ne wani nau'i na kwayoyi da ake amfani dasu don magance cututtuka na rheumatoid . Babban mai gabatarwa JAK, Xeljanz (tofacitinib citrate) , ya amince da FDA a ranar 6 ga Nuwamba, 2012. Wasu suna cikin ci gaba. Juyin juyin JAK ne a matsayin magani ga cututtukan cututtuka na rheumatoid ya zo a kan sheqa na ci gaba a cikin ilimin rigakafi da kwayoyin halitta wanda ya haifar da cigaban kwayoyin halitta .
Bari mu gano muhimmancin JAK masu hanawa a cikin tsarin rigakafi da kuma kula da maganin ƙwayar cuta.
Cytokines bayyana
Yawancin mutanen da ke dauke da cututtukan arthritis (da sauran cututtukan cututtukan cututtuka) tabbas ba su san abin da ba a sani ba da lokacin kiwon lafiya, cytokines , kafin a yi amfani da miyagun ƙwayoyi na zamani, Enbrel (etanceptcept) , a shekarar 1998. Domin fahimtar yadda kwayoyin kwayoyi ke aiki, marasa lafiya sun samu hadarin hanya a cikin ilimin rigakafi.
Marasa lafiya sunyi bayanin cewa cytokine sunadaran sunadarai wanda aka samo daga kwayoyin halitta kuma suna da hannu wajen tsara maganganun kumburi . Cytokines yi hulɗa tare da tsarin kwayoyin cuta don tsara tsarin mayar da martani game da cututtuka da kamuwa da cuta - da kuma daidaita hanyoyin tafiyar salula ta jiki. Cytokines suna da hannu wajen maganganu masu mahimmanci. Akwai hanyoyi daban-daban na cytokines.
An halicci kwayoyin halitta don tsoma baki tare da aikin cytokine (misali, don hana ko toshe TNF (magungunan necrosis tumor) da kuma dama daga cikin interleukins (IL-1, IL-6, IL-17, IL-12/23), don hana sigina na biyu da aka buƙata don shigar da T-cell, da kuma ƙaddamar da ƙwayoyin B.
Duk da yake kwayoyi masu magungunan kwayar halitta suna da nau'o'in daban-daban a cikin tsarin da ba a rigakafi, burin shine iri ɗaya-don yaduwa da kwayoyin cututtuka , don haka yana kula da cutar rheumatic .
Ƙananan Magungunan Ƙauren Ƙwayoyi ga Rheumatoid Arthritis
Ba a ƙayyade magungunan JAK ba ne a matsayin likita. Maimakon haka, an ƙaddara shi a matsayin ƙananan kwayoyin DMARD (maganin ƙwayar cuta mai tsari).
Manufar mai hana JAK ita ce hanya ta JAK wadda ita ce hanya ta nuna alama a cikin sel wanda ke da muhimmiyar rawa a cikin tsarin mai kumburi da ke hade da cutar arthritis. Musamman, JAKs (Janus kinases) su ne ƙananan enzymes (wato, protein cytoplasmic protein tyrosine kinases) wanda ke watsa sigina daga masu karɓar cytokine masu yawa zuwa tsakiya na sel.
Akwai rahotanni fiye da 500 a cikin 'yan' yan adam kuma an raba su zuwa takwas. Jaks suna cikin dangin kin-kinalcin kinzine tyrosine - iyali wanda ke da mambobi 90. Yanayin Janus kinase (JAK) sun haɗa da TYK2, JAK1, JAK2, da JAK3.
Da zarar masu bincike sun fahimci muhimmancin da JAKs ke takawa a cikin siginar cytokine, sun zama mafi mahimmanci akan nazarin asibiti. Tofacitinib shi ne mai gabatarwa na farko na JAK da za'a gwada shi a asibiti da kuma yarda da cutar arthritis. Tofacitinib, wanda Pfizer, Inc. ya haɓaka, ya hana JAK3 da JAK1, da JAK2 zuwa ƙananan digiri. Tofacitinib ba zai shafi TYK2 ba.
Tofacitinib-Mai gabatarwa na farko na JAK da aka amince don Arthritis Rheumatoid
Tofacitinib (sunan mai suna Xeljanz) an yarda da shi a matsayin magani ga tsofaffi tare da matsakaici-zuwa mai tsanani mai cututtukan zuciya wanda yake da rashin dacewar amsawa ko rashin haƙuri ga methotrexate .
Xeljanz magani ne mai mahimmanci, wanda yake samuwa a matsayin kwaya 5 mg wanda za a dauka sau biyu a kowace rana. Ana iya ɗauka tare da ko ba tare da abinci ba. Har ila yau, akwai nau'i na 11 mg a kowace rana, wanda ake kira Xeljanz-XR (ƙarin saki). Xeljanz za a iya ɗaukar shi kadai (watau, ana amfani dasu), ko kuma za'a iya hade shi tare da hanya ko wasu daga cikin DMARDs marasa ilimin halitta. Xeljanz bai kamata a yi amfani da kwayoyi ba.
Tsaro na JAK Mai Rikicin Kwayoyi
Kamar yadda aka tantance lafiyar game da Xeljanz (tofacitinib), masu bincike sun kammala ya kasance kamar kwayoyin halitta. Akwai haɗarin hadarin cututtuka, ƙananan haɗuwar haɗari tare da aikin hanta , da kuma yiwuwar neutropenia (ƙananan neutrophils, nau'in jini na jini), hyperlipidemia (ƙananan lipids ko fats a cikin jini), da kuma tsararren halitta na creatinine tare da tofacitinib amfani.
An buƙaci umarnin Akwatin Black a matsayin wani ɓangare na yarda da lakabi na tofacitinib don yayi gargadi game da waɗannan cututtuka masu tsanani.
Baricitinib
Baricitinib shine mai gabatarwa na JAK na biyu don mika wani aikace-aikacen NDA (New Drug Application) zuwa FDA a watan Janairun 2016. FDA ta kara tsawon lokacin dubawa don Baricitinib don ba da damar yin nazari na ƙarin bayanai da mai ba da magani, Lily da Incyte suka bayar. An ba da ƙarin bayanai don amsawa ga FDA Information Request. Ƙarin bayani an gani a matsayin babban haɓakawa zuwa na NDA na ainihi kuma yana ƙara watanni 3 zuwa lokacin bita.
A watan Disamba na shekara ta 2016, kwamitin kula da magungunan maganin magunguna na Turai (CHMP) ya bada shawarar bada izinin kasuwanci a Tarayyar Turai (EU) don Olumiant (baricitinib). Baricitinib ya bada shawara don kula da tsofaffi tare da ciwon maganin arthritis mai matsakaici da matsananciyar wahala wadanda ba su da amsa da kyau ga, ko kuma wadanda basu iya jurewa daya ko fiye da kwayar cutar anti-rheumatic (DMARDs).
Baricitinib wani mai gabatarwa JAK1 / 2 na yau da kullum ya nuna don maganin matsakaicin matsananciyar cututtuka na arthritis. Bayanan jarrabawar jarrabawa sun nuna matukar cigaba a ciwo, gajiya, aiki na jiki, da kuma lafiyar lafiyar lafiyar jiki a cikin marasa lafiya da ba a yaye ba a baya da kuma waɗanda suka kasa sauran kwayoyi.
Kalma Daga
Don sake gwadawa, an haramta masu hanawa JAK a matsayin ƙananan kwayoyi DMARDs, ba kwayoyin kwayoyin halitta ba. Babban bambanci shi ne cewa masu hana maganin JAK suna aiki a cikin kwayoyin halitta (cikin kwayoyin halitta) da kwayoyin halittu sunyi niyya (misali, masu karɓa a farfajiyar sel). Har ila yau, masu maganin JAK sune kwayoyi ne na kwayoyi, yayin da kwayoyin halittu sun yi inganci ko sunyi amfani da jiko.
Tun da yake mutanen da ke dauke da maganin maganin ƙwaƙwalwar ƙwayar cutar ba duk suna da irin wannan maganin ba, yana da mahimmanci don bunkasawa da kuma samar da sababbin hanyoyin maganin. Bugu da ƙari, tofacitinib da baricitinib waɗanda aka tattauna a sama, ƙaddamar da gwaji na zamani III suna ci gaba ta amfani da filgotinib da ABT-494-dukansu masu hana JAK1.
> Sources:
> Furst, Daniel E., MD. Bayani na Ma'aikatan Halitta na Halitta da Magunguna a cikin Rheumatic Diseases. Na zamani. Updated Fabrairu 2, 2017.
> McInnes, Iain B., PhD. Cytokine Networks a Cikin Rheumatic Cututtuka: Abubuwa na Far. Na zamani. Updated Nuwamba 5, 2015.
> Nakayamada, S. et al. Ci gaban kwanan nan a cikin JAK masu hanawa don maganin cututtukan Arthritis Rheumatoid. BioDrugs. Oktoba 2016.
> O'Shea, John J. et al. Janus Kinase Masu maganin cututtuka a cututtuka na Autoimmune. Annals na Rheumatic Diseases. Afrilu 2013.
> Elvidge, Suzanne. Bayanin FDA na Rushewa akan Lilly da Incyte ta Arthritis Drug. BiopharmaDIVE. Janairu 17, 2017.