Yin maganin ƙaiƙayi na DEB tare da ƙananan ƙwayoyin cuta (2022)

Ƙungiyoyin mutane uku sun shiga cikin binciken PRUMEC: mutanen da ke da DEB-pruriginosa, da ƙungiyoyin 'control' guda biyu: mutanen da ke da DEB (ba pruriginosa) da masu sa kai ba tare da EB ba.

Sakamakon kwatanta fata da samfurori na jini daga ƙungiyoyi uku sun nuna cewa amsawar tsarin rigakafi (ƙumburi) a cikin fata, maimakon a cikin jini, suna da alhakin ƙaiƙayi. Wannan kumburi ya kasance nau'ikan maɓalli guda biyu, ɗayan yana cikin eczema kuma ɗayan yana cikin psoriasis, yana ba da shawarar cewa ana iya sake dawo da magunguna don waɗannan yanayin yadda ya kamata don magance EB itch.

Masu binciken sun yi shirin gudanar da gwaje-gwaje na asibiti don ba da shaida cewa waɗannan magungunan suna aiki a cikin EB ta yadda, a nan gaba, za a iya ba su lasisi da kuma amfani da su akai-akai don inganta rayuwar EB.

Masu bincike buga wani bita a cikin mujallar British Association of Dermatology Journal a cikin 2021 da kuma wasu sakamako a cikin labarin mai suna "Fahimtar bayanan da aka rubuta na recessive dystrophic epidermolysis bullosa fata rauni yana nuna damar sake dawo da miyagun ƙwayoyi don inganta warkar da rauni.".

Shugabannin Bincike:
Farfesa John McGrath MD FRCP FMedSci Farfesa ne na Kwayoyin cututtukan fata a Kwalejin King na London kuma Shugaban Sashin Cututtukan Fatar Halittu, da kuma Babban Mashawarcin Likitan fata a St John's Institute of Dermatology, Guy's da St Thomas' NHS Foundation Trust a Landan. A baya ya kasance ɗan ƙaramin ɗan bincike na EB mai tallafi na DEBRA kuma ya yi aiki akan binciken EB sama da shekaru 25. Yanzu yana jagorantar da haɗin kai akan ayyuka da yawa na ƙasa da ƙasa don haɓaka kwayoyin halitta, tantanin halitta, furotin da magungunan ƙwayoyi waɗanda zasu iya haifar da ingantattun jiyya ga mutanen da ke zaune tare da EB.

Farfesa Jemima Mellero Mashawarcin Likitan fata ne kuma farfesa a St John's Institute of Dermatology, Guy's da St Thomas' NHS Foundation Trust. Tana da fiye da shekaru 20 tana aiki a asibiti a fannin EB da sauran cututtukan fata na kwayoyin halitta, da kuma bayanan bincike da ke kallon tushen kwayoyin halitta na nau'ikan EB daban-daban, da gwaje-gwajen asibiti zuwa sabbin hanyoyin kwantar da hankali na EB kamar fibroblast da mesenchymal stromal cell. far. Ta sadaukar da ita don ci gaba da wannan aikin don haɓaka ingantattun jiyya ga kowane nau'in EB.

"Daya daga cikin alamun da ke damun mutane masu EB shine ƙaiƙayi. A halin yanzu, mun san kadan game da abin da ke haifar da ƙaiƙayi kuma ma kaɗan game da yadda za mu bi da shi. Muna farin cikin samun tallafin DEBRA don yin aiki akan ƙaiƙayi. Za mu yi nazarin mutane tare da wani nau'i mai nau'i na EB mai suna EB pruriginosa. Mun kuma shirya gudanar da gwajin asibiti na ƙwayoyin kasusuwan kasusuwa da muke fata za su rage ƙaiƙayi da inganta fatar EB.”

Farfesa John McGrath

Sunan baiwa: Ƙimar farkon ingancin ƙwayoyin allogeneic mesenchymal stromal da ake gudanarwa ta cikin jini akan itching a cikin manya tare da epidermolysis bullosa Pruriginosa (PRUMEC - PRUSTEM).

An raba wannan tallafin bincike zuwa matakai biyu - PRUMEC da PRUSTEM.
Mataki na 1 - PRUMEC Nazarin injin-sarrafawa na ƙwayar cuta (itch) a cikin manya tare da dystrophic epidermolysis bullosa pruriginosa.
Mataki na 2 - PRUSTEM - Kimantawa na farkon inganci na allogeneic mesenchymal stromal sel da ake gudanarwa ta cikin jini akan itching a cikin manya tare da epidermolysis bullosa Pruriginosa.

Abstract
Wannan bincike game da ƙaiƙayi ne a cikin epidermolysis bullosa (EB). Mun san cewa itching alama ce ta kowa kuma mai ban sha'awa, kuma mafi kyawun sarrafa ƙaiƙayi shine muhimmin fifikon bincike ga mutanen da ke zaune tare da EB. A halin yanzu, ba a fahimci dalilin da yasa fata ke ƙaiƙayi a EB ba kuma mun san cewa yawancin jiyya na yanzu ba su da tasiri musamman.
Gwaje-gwaje na asibiti na baya na wani nau'i na maganin kwayar cutar sun dauki kwayoyin kasusuwa na kasusuwa (mesenchymal stromal cells, MSCs) daga masu ba da gudummawa marasa lafiya da ba su da alaka da su ta hanyar jijiya a cikin yara da manya tare da EB dystrophic recessive; waɗannan gwaje-gwajen ana kiran su EBSTEM da ADSTEM kuma sun nuna cewa ƙwayoyin suna da lafiya kuma a yawancin mutane jiko na tantanin halitta suna da fa'idodi masu kyau don warkar da rauni, ciwon fata da ƙaiƙayi.

Wannan aikin zai bincika hanyoyin da ke da tushe da yuwuwar maganin ƙaiƙayi a cikin EB za a raba shi zuwa matakai biyu, PRUMEC da PRUSTEM.

Mataki na 1 - PRUMEC

Wannan bincike ne mai sarrafa shari'a, (nau'in binciken lura wanda ya ƙunshi ƙungiyoyi 2 ko fiye) wanda ke nufin sanin ko ƙungiyoyin suna da sakamako daban-daban bayan binciken. Kamar yadda wannan binciken injiniya ne, wannan yana nufin binciken yana nufin fahimtar hanyoyin nazarin halittu a bayan pruritus (itch) da kuma gano maƙasudin magani don wannan.
Tunda wannan binciken ya ƙunshi nazarin hanyoyin da ke haifar da pruritus, za a sami ƙungiyoyi daban-daban guda 3:

1. 10-30 manya tare da dystrophic epidermolysis bullosa pruriginosa (DEB-P), wanda za a yi fata da jini da aka dauka kuma idan aka kwatanta da,
2. 10-30 manya tare da nau'in DEB mara-pruriginosa (DEB-NP), da
3. 10-30 masu aikin sa kai masu lafiya a matsayin ƙungiyoyin sarrafawa.

Za a daidaita majinyatan da aka ɗauka idan zai yiwu, daidai da abin da ke aiki a asibiti da dabaru, dangane da shekaru, jinsi, ƙabila, tsananin EB, lokacin biopsy da wurin biopsy. Za a ɗauki tambayoyin tambayoyi da samfuran jini da fata daga kowace ƙungiya sama da wata 12. Wannan zai ba da damar kwatanta tsakanin ƙungiyoyi.

Mataki na 2 - PRUSTEM (gwajin Mataki na I/II)

Wannan mataki zai biyo bayan kammala PRUMEC, inda rukunin rukunin marasa lafiya na DEB-P za a ba su samfurin magani dangane da sakamakon PRUMEC. Za a maimaita gwaje-gwajen jini, tambayoyin tambayoyi da biopsies kamar yadda suke a cikin binciken PRUMEC kuma idan aka kwatanta da ƙididdigar asali da aka yi a matakin farko.

Samfurin magani zai kasance a cikin nau'in maganin tantanin halitta inda har zuwa manya 10 tare da EB pruriginosa kowannensu zai karɓi 3 infusions na MSCs. Wannan aikin zai auna ƙaiƙayi ta amfani da cikakken tsarin ƙira mai suna Leuven Itch Scale, wanda aka gwada a baya a EB. Za a bincika fata da jini bayan an gudanar da maganin tantanin halitta don bincika yadda ƙwayoyin cuta za su yi aiki wajen rage ƙaiƙayi da kwatanta sakamakon da aka ɗauka a baya.

Hakanan za a kwatanta sakamakon da jinin mutane 10 tare da DEB - NP da 10 masu kula da batutuwa waɗanda ba su da EB daga binciken PRUMEC. Waɗancan mutane ba za su karɓi maganin tantanin halitta na MSC ba, amma samfuran su za su taimaka wajen ƙoƙarin gano abin da ke haifar da EB pruriginosa mai ƙaiƙayi da fari.

Babban manufar wannan aikin shine don inganta fahimta game da (a) abin da ke haifar da ƙaiƙayi a cikin EB pruriginosa (da yiwuwar wasu nau'ikan EB), (b) ko infusions na MSC na cikin jini yana ba da magani mai taimako ga mutanen da ke da EB pruriginosa da, (c). ) ta yaya MSCs ke aiki wajen rage raɗaɗi a cikin EB pruriginosa. Ana fatan cewa sakamakon haɗin gwiwar EBSTEM, ADSTEM da PRUSTEM / PRUMEC za su bayyana fa'idodin wannan nau'i na maganin tantanin halitta ga mutanen da ke da DEB (da yiwuwar wasu nau'o'in EB) da kuma samar da hanzari don ci gaban MSC cell far a matsayin wani ɓangare. na kulawar asibiti na yau da kullun don DEB.

PRUMEC: Nazarin injin sarrafa shari'a na pruritus a cikin manya tare da dystrophic epidermolysis bullosa pruriginosa.

Itch yana daya daga cikin mahimman matsalolin mutanen da ke fama da epidermolysis bullosa (EB). Yana da mahimmanci musamman kuma mai tsanani a cikin nau'in dystrophic na EB (DEB). An yi bincike mai zurfi game da hanyoyin ƙaiƙayi a cikin yanayin fata na yau da kullun a cikin shekaru ashirin da suka gabata, wanda ya ƙara fahimtarmu don haka ikon samar da ingantattun jiyya don shi. Duk da haka, ba a yi nazarin ƙaiƙayi a cikin DEB ba har zuwa wannan matsayi kuma mafi mahimmanci, magungunan da za su iya ragewa ko dakatar da shi yadda ya kamata ba su samuwa ga wannan rukuni. Don haka mun shirya binciken bincike, da nufin gano abin da ke haifar da ƙaiƙayi a cikin matsanancin ƙaiƙayi na DEB, wanda aka sani da pruriginosa. Babban burinmu shine gano hanyoyin da za mu iya kaiwa hari da toshewa da kwayoyi, don kawar da ƙaiƙayi.

Don wannan binciken, mun ɗauki mahalarta zuwa ƙungiyoyi uku: mutanen da ke da DEB pruriginosa (DEB-P), tare da ƙungiyoyin 'iko' guda biyu na mutanen da ke da DEB ba tare da fata mai laushi ba da kuma mutanen da ba tare da fata ko wasu yanayin kiwon lafiya ba (masu aikin sa kai masu lafiya, HV) . Masu shiga cikin ƙungiyoyin sarrafawa sun dace da mahalarta DEB-P kamar yadda zai yiwu don shekaru, jinsi da kabilanci, domin mu tabbatar da cewa bambance-bambancen da aka gani tsakanin ƙungiyoyi a lokacin gwaje-gwajen ba za a iya haifar da bambance-bambance a cikin kowane ɗayan waɗannan sigogi tsakanin su ba. kungiyoyin. Kowane ɗan takara ya kammala ziyarar bincike 2-3 tare da mu. A yayin waɗannan, mun tantance tsananin EB da girman a cikin ƙungiyoyin DEB guda biyu ta amfani da makin da aka sani da EBDASI kuma mun tambayi mahalarta DEB su cika takardar tambaya kan tasirin EB akan ingancin rayuwarsu (QoL). Mahalarta DEB-P kuma sun kammala ingantattun ma'auni guda biyu suna tantance bangarorin ƙaiƙayi, kamar tsananin ƙarfi, mita da tsawon lokaci, waɗanda aka sani da Sikelin Leuven Itch Scale (LIS) da sikelin 5D. Mun dauki samfuran jini daga duk mahalarta da kuma biopsies na fata daga mahalarta waɗanda suka yi farin cikin yin haka. An yi gwajin gwaji a cikin jini don auna alamun kumburi da kuma tabbatar da cewa mahalarta ba su da wasu matsalolin da za su iya haifar da ƙaiƙayi, irin su atop, hanta ko aikin koda. Samfuran fata daga DEB-P da mahalarta DEB-NP an ɗauke su daga duka wuraren da aka shafa (rauni) da kuma waɗanda ba su da lahani (marasa lahani) na fata.

Daga baya mun yi jerin gwaje-gwaje a kan jini da fata don tantance matakan bayyana kwayoyin halitta da sunadarai. An kwatanta waɗannan matakan tsakanin DEB-P da ƙungiyoyin sarrafawa guda biyu.

An yi shawarwari da yawa bisa sakamakon.

Musamman ma, ya bayyana a lokacin binciken cewa ga mutanen da ke da DEB-P an iyakance itching zuwa wuraren da aka shafa (ja, blistered ko rauni) na fata. Wannan babban abin lura ne wanda ke nuna cewa babu wani dalili na tsari na ƙaiƙayi, amma tsarin tafiyar da shi yana iyakance ga fata, musamman ga raunukan fata.

Alamun ƙumburi a cikin jini sun nuna cewa akwai ƙarin kumburi a cikin fata na DEB-P idan aka kwatanta da DEB maras ƙaiƙayi, kamar yadda za mu iya godiya lokacin kallon fata tare da ido tsirara ko a karkashin wani microscope.

Mummunan cuta da tasiri akan QoL duka sun ƙaru a cikin DEB-P. Ƙunƙarar ƙaiƙayi mai yiwuwa ne ya haifar da waɗannan binciken, saboda yana matukar shafar barcin mutane, zamantakewar jama'a da kuma ayyukan yau da kullun, yayin da kullun fata yana haifar da sabbin kusoshi da raunuka.

Abin sha'awa shine, tsananin itching ya yi daidai da matakan alamun kumburi a cikin jinin mutane na DEB-P, yana nuna dangantaka mai mahimmanci tsakanin ƙaiƙayi da kumburin fata. Wannan yana nuna cewa idan muka mayar da hankali kan nazarin kumburi a cikin fatar mutanen da ke da DEB, da alama hakan zai taimaka mana mu fahimta, don haka magance ƙaiƙayi cikin nasara.

Motsawa zuwa ƙarin takamaiman binciken a matakin salula da kwayoyin halitta, bincikenmu a cikin jini ya nuna cewa yawancin masu shiga tsakani na kumburi ba a tashe su a cikin jini na DEB-P idan aka kwatanta da sarrafawa. Wannan yana nufin cewa ko dai har yanzu kayan aikinmu ba su da hankali sosai don gano bambance-bambancen da ke wurin, ko kuma kumburin yana iyakance ga fata kuma baya zubewa zuwa wurare dabam dabam. Dangane da wannan, ba a sami bambance-bambance masu mahimmanci a cikin matakan maganganun kwayoyin halitta a cikin jini tsakanin ƙungiyoyi ba. Koyaya, ma'auni na gaba ɗaya na sunadaran sunadaran cikin jini sun ba da shawarar cewa ƙwayoyin jini da aka sani da platelet, waɗanda ke da hannu cikin samuwar ɗigon jini ana kunna su a cikin DEB-P idan aka kwatanta da duka sarrafawa. Wannan al'amari duk da haka bai keɓance ga DEB-P ba kuma an kwatanta shi a wasu yanayi inda fata ke kumburi da ƙaiƙayi.

An samo mafi mahimmancin binciken wannan binciken daga kwatanta fata da aka shafa na mutanen DEB-P tare da fatar da ba ta dace ba da aka dauka daga yankunan da ke kusa a cikin waɗannan mutane guda ɗaya, da kuma biopsies daga wannan shafin da aka dauka daga DEB-NP da HV. Da fari dai, kwayoyin halitta da furotin a cikin marasa lafiya, fata marasa ƙaiƙayi na mutanen DEB-P duka sun yi kama da waɗanda ke cikin fata mai lafiya daga DEB-NP da HV. Ya kasance lokacin da muka kwatanta raunin fata na DEB-P tare da fata na al'ada daga DEB-P, DEB-NP da HV, an ga bambance-bambance. Musamman ma, an gano hanyoyin da ke da alaƙa da rigakafi da yawa a cikin raunin DEB-P. Hanyoyi guda biyu daban-daban sun zama kamar sun mamaye martanin tsarin rigakafi a cikin fata. Kwayoyin halitta da yawa suna shiga cikin waɗannan hanyoyin (ko abin da ake kira 'inflammatory cascades'), wasu daga cikinsu za mu iya toshewa tare da sababbin tsararraki, magungunan da aka yi niyya sosai da aka sani da ilimin halitta. An riga an yi amfani da waɗannan magungunan don eczema da psoriasis a aikin asibiti kuma ana ɗaukar su lafiyayye. Kwayoyin halitta ba su kasance wani ɓangare na maganin EB a al'ada ba, duk da haka sakamakon wannan binciken ya ba mu dalili mai kyau don yin imani cewa za su iya zama da amfani wajen rage kumburi, sabili da haka ƙaiƙayi, a cikin fata na mutanen da ke da EB dystrophic. A mataki na gaba na binciken mu, muna shirin gwaje-gwaje na asibiti inda za mu gwada wasu daga cikin waɗannan wakilai a cikin DEB. Muna fatan samar da shaidar da za ta ba mu damar samar da waɗannan magunguna akai-akai ga mutanen da ke da DEB a cikin yanayin asibiti. (Daga rahoton ci gaba na ƙarshe na 2022.)