Fesa akan jigon halittar RDEB (2022)

An ƙirƙiri sabbin ƙwayoyin cuta guda biyar na maganin ƙwayoyin cuta kuma a halin yanzu ana nazarin su don ganin yadda suke maido da furotin collagen da ya ɓace a cikin sel daga majinyatan RDEB.

Kwayoyin fata, da ake kira keratinocytes da fibroblasts, an girma a cikin dakin gwaje-gwaje kuma an nuna su a karon farko don haɗa kansu a cikin yadudduka kamar yadda aka gani a fata bayan fesa.

Wani nau'in fibroblast na musamman yana taimakawa warkarwa ba tare da tabo ba kuma an samu nasarar tattara su kuma an girma a cikin dakin gwaje-gwaje daga sel masu haƙuri na RDEB kuma a daskare don amfani a gaba.

An gwada tsarin aikin jiyya na ƙwayar cuta ta hanyar fesa ta yadda gwajin asibiti zai sami damar ci gaba idan ɗayan sabbin zaɓuɓɓukan jiyya na ƙwayoyin cuta guda biyar suna aiki da kyau a cikin sel.

Masu bincike buga wani bita na yuwuwar aikin su a ƙarshen 2021 da yi rajistar nazari na yau da kullun a cikin 2022. A watan Mayu 2022 Dr Lwin da Farfesa McGrath sun amince da tallafi daga DEBRA UK a cikin labarin mai suna. Maidowa nau'in VII collagen a cikin fata.

Lemai binciken talla: Dr Su Lwin magatakarda ne na Likitan cututtukan fata kuma ƙwararren Bincike na Clinical a St John's Institute of Dermatology, Guy's da St Thomas' NHS Foundation Trust, da King's College London. Ta kasance tana aiki akan binciken EB a matsayin Jagoran Binciken Clinical Research Fellow akan nau'ikan majagaba da yawa da gwaje-gwaje na asibiti tun daga 2014 lokacin da ta shiga Lab ɗin Farfesa John McGrath, gami da gwajin EBSTEM, GENEGRAFT da LENTICOL-F. Ta ci gaba da yin haɗin gwiwa tare da abokan aiki na ƙasa da na duniya don sadaukar da bincikenta don haɓaka ingantattun hanyoyin kwantar da hankali na asibiti ga mutane masu EB.

Masu bincike:
Farfesa John McGrath MD FRCP FMedSci tana rike da kujerar Mary Dunhill a likitancin cuta a Kwalejin King London kuma ita ce Shugabar Sashin Cututtukan Fatar Halitta, da kuma mai ba da shawara ga likitan fata a St John's Institute of Dermatology, Guy's da St Thomas' NHS Foundation Trust a Landan. Babban abubuwan da ya fi sha'awa shine a cikin kwayoyin halitta da kuma maganin farfadowa da kuma yadda waɗannan tasiri akan dermatology da cututtukan fata. Yana da hannu a cikin shirye-shiryen tsara tsararraki da yawa na gaba don inganta bincike don maganin genodermatoses kuma shine babban mai bincike don yawancin gwajin asibiti na farkon lokaci na ƙwayoyin cuta da ƙwayoyin jijiya ga marasa lafiya da cututtukan fata da aka gada.

Dr Michael Antonio shi ne shugaban kungiyar Gene Expression and Therapy Group a cikin Sashen Kiwon Lafiya da Kwayoyin Halittu na Kwalejin King London, inda ya kasance tun 1994. Abubuwan bincikensa sun hada da binciken mahimman hanyoyin sarrafa kwayoyin halitta da kuma yin amfani da waɗannan binciken don haɓaka hanyoyin warkewa na tushen kwayoyin halitta. samfurori. Tare da abokan haɗin gwiwa a masana'antu, Dr Antoniou ya haɓaka ingantaccen dandamalin maganganun kwayoyin halitta (Fasaha na UCOE®) don kera sunadaran warkewa kamar ƙwayoyin rigakafi da kuma amfani da magungunan ƙwayoyin cuta. Har ila yau, ya samar da maganin maganin kwayoyin halitta wanda a halin yanzu yana cikin gwaje-gwaje na asibiti a Italiya don rashin lafiyar jini b-thalassaemia. Gabaɗaya ƙungiyar Dr Antoniou jagora ce a cikin haɓaka magungunan ƙwayoyin cuta waɗanda za su iya aiki cikin ingantaccen haifuwa da kwanciyar hankali don haka suna ba da ingantaccen magani na dogon lokaci. Dangane da wannan, gudummawar Dr Antoniou ga wannan aikin zai kasance mai mahimmanci don samun sakamako mai dorewa na warkewa biyo bayan jiyya na jiyya na marasa lafiya RDEB.

Masu haɗin gwiwa:
Farfesa Alain Hovnanian da Dr Matthias Titeux, INSERM UMR 1163, Imagine Institute, Paris, Faransa.

“Ana matukar buƙatar hanyoyin kwantar da hankali ga masu haƙuri don RDEB. Wannan rukunin ya ba da shawarar magance wannan ƙalubalen ta hanyar haɓaka maganin feshi akan kwayoyin halitta don RDEB wanda aka ƙera don fa'idar warkewa mai ɗorewa mai ɗorewa gami da rigakafin tabo"

Dr Su Lwin

Grant Title: Preclinical binciken fesa-on gene far for recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) yana daya daga cikin mafi tsanani siffofin EB tare da gagarumin cuta nauyi da kuma high mace-mace saboda cutaneous squamous cell carcinoma (cSCC). Sakamakon maye gurbi a cikin kwayar halittar COL7A1 wanda ke samar da nau'in collagen na VII, yana haifar da blisters da raunin nama. Ana samun kulawar kwantar da hankali kawai a halin yanzu; don haka, ingantattun hanyoyin kwantar da hankulan marasa haƙuri buƙatu ne da ba a cika su ba. Wannan rukunin ya ba da shawarar magance wannan ƙalubalen ta hanyar haɓaka maganin feshi akan kwayoyin halitta don RDEB wanda aka tsara don fa'idar warkewa mai dorewa, gami da rigakafin tabo.

Gina kan gwaji na asibiti na kwanan nan na jiyya, Lenticol-F, shirin shine don ƙara ƙwayoyin fata na RDEB masu haƙuri tare da kwafi na aikin COL7A1 gene. Don cimma wannan, sun yi hasashen yin amfani da wani nau'i na nakasassun ƙwayoyin cuta mai suna lentivirus don sadar da kwayar halitta zuwa keratinocytes da fibroblasts sannan a fesa su a kan fatar da ta shafa tare da taimakon SkinGun™ wanda kamfanin biotech ya tsara. RenovaCare.

Da farko, aikin zai nemi samar da hujja-na-ra'ayi da kuma kimanta ko fesa Kwayoyin samar da aiki fata ta amfani da dabba model. Manufar su ita ce tantance ingantacciyar hanyar da waɗannan ƙwayoyin cuta ke isar da kwayar halitta mai aiki ga sel na marasa lafiya da kuma tabbatar da ko amfanin warkewar yana daɗewa.

Dogaro da aikace-aikacen fesa tantanin halitta don isar da lambar ƙirar halitta don nau'in VII collagen zai kawar da buƙatar hanyoyin ɓarna da kuma ba da jiyya mai dacewa da haƙuri. Bugu da ƙari, ƙwayoyin da aka haɓaka kwayoyin halitta za a iya girma da sauri kuma a adana su a cikin ƙananan zafin jiki har sai majiyyaci ya shirya don karɓar su, wanda zai inganta ingantaccen aikin asibiti na maganin kwayoyin halitta.

Wannan hoton yana kwatanta tsarin da aka tsara na fesa-kan kwayoyin cuta/hanyoyin farfaganda na RDEB.

Wannan tallafin zai ba masu binciken damar samun mahimman bayanai na maganin fesa-kan da ake buƙata don aikace-aikacen ɗan adam wanda za a iya samar da shi cikin sauƙi don amfani da asibiti, don haka yana amfana da fa'idar yawan mutane tare da RDEB.

Fesa-on gene far for recessive dystrophic epidermolysis bullosa: Pre-clinical Nazarin lentiviral-mediated COL7A1- supplemented epidermal kara cell da CD39 + CD26- fibroblast spray-on far.

Wannan aikin bincike yana mai da hankali kan recessive dystrophic epidermolysis bullosa (RDEB), mafi tsananin nau'in EB. RDEB yana faruwa ta rashin lahani COL7A1 kwayoyin halitta wanda hakan ke haifar da rashi ko rashin aiki nau'in furotin VII collagen (C7). C7 yana samar da sifofi masu kama da ƙugiya da ake kira anchoring fibrils (AFs) waɗanda ke riƙe da saman epidermis da ƙananan yadudduka na fata. A cikin RDEB, rashin ƙarfi ko rashin aiki C7 da AFs masu riƙe da dermis da epidermis suna haifar da blisters da yashwa da raunuka na yau da kullum. Don neman ingantacciyar magani ga RDEB, mun ba da shawarar gudanar da jerin gwaje-gwaje na tushen lab a cikin dakunan gwaje-gwaje a Kwalejin King London da kuma a INSERM a Paris, tare da haɗin gwiwar abokin aikinmu na masana'antar RenovaCare Inc. don magance abubuwan da ba a cika bukatun RDEB ba. ta hanyar haɓaka maganin feshi-kan ga mutanen da ke da RDEB, wato aikin Spraycol.

A taƙaice, akwai sabbin sabbin abubuwa guda uku ga wannan aikin: ingantacciyar fasaha mai ɗorewa kuma mai ɗorewa ta fasahar jiyya ta ƙwayoyin cuta, na'urar da ke da alaƙa da haƙuri, na'urar isar da iska mara amfani ta amfani da SkinGun™ daga kamfanin fasahar kere kere RenovaCare Inc., da kuma sauri na asibiti-fassarar hanya.

Duk da kalubalen da ba a taba ganin irinsa ba na jinkirin ayyukan, hana tafiye-tafiye da rufe iyakoki saboda bala'in duniya, da mutuwar memba na masana'antar mu, an sami ci gaba mai zuwa:

1. Mun yi nasarar ginawa tare da haɗa sabbin hanyoyin samar da jiyya na zamani guda biyar ta amfani da nau'in ƙwayar cuta naƙasassu, wanda aka ƙera don ingantacciyar inganci wajen isar da kwayar halittar COL7A1 zuwa ƙwayoyin marasa lafiya na RDEB. Ana tabbatar da waɗannan a halin yanzu don dacewa da ingancin su na maido da furotin C7 da ya ɓace a cikin ƙwayoyin marasa lafiya.
2. Wani muhimmin sashi na wannan aikin shine ya nuna cewa sel daga sama da ƙananan yadudduka na fata - keratinocytes da fibroblasts, da zarar an fesa su, suna iya haɗuwa da kansu a cikin irin wannan yanayin zuwa fata na mutum. Don yin wannan, dole ne mu samar da keratinocytes da fibroblasts da aka yi wa alama tare da launi daban-daban guda biyu - ja da kore, don mu iya ganin su kuma mu lura da halayen su a ƙarƙashin microscope. An samar da waɗannan sel masu alamar, tare da sel marasa alama kuma an yi nasarar fesa su don ganin ko an samar da tsarin fata mai launi biyu bayan fesa. Daga waɗannan gwaje-gwajen, mun nuna shaidar farko kan warkar da rauni ta hanyar fesa akan ƙwayoyin fata na ɗan adam da kuma sel masu haƙuri na RDEB da aka gyara.
3. Mun kuma nuna cewa yawan jama'a na RDEB fibroblast sel, wanda ke da mahimmanci don rage tabo lokacin da raunin rauni ya faru, an samu nasarar keɓewa daga ƙwayoyin marasa lafiya kuma suna da lafiya. Mun kuma nuna cewa hanyar keɓewa da ake amfani da ita don wadatar da wannan ƙaƙƙarfan jama'a ba ta hana ƙwayoyin sel girma ba wanda ke ba mu damar haɓaka ƙwayoyin sel da daskare su don amfani a gaba. Wannan yawan jama'a na fibroblasts yana da ban sha'awa musamman saboda suna da kaddarorin musamman a cikin warkar da rauni ba tare da haifar da tabo ba.

Ta wannan aikin, mun yi amfani da damammaki na musamman waɗanda za su ba da damar sauri zuwa fassarar asibiti na maganin feshi akan kwayoyin halitta ta hanyar haɗin gwiwa tare da abokan hulɗarmu na duniya na dogon lokaci daga INSERM, Paris da CIEMAT, Madrid ta hanyar gwada magungunan su na marayu da aka keɓe na maganin kwayoyin halitta. ginawa.

An koyi darussa masu yawa ta wannan binciken.

Na farko, mun koyi cewa fesa ƙwayoyin fata na ɗan adam (fibroblasts da keratinocytes) suna da 'ilimin' na ciki na yadda za a daidaita kansu da zarar an fesa fata a kan rauni (bincikenmu na yanzu ya nuna wannan). A wasu kalmomi, sel daga ƙananan fata na fata - fibroblasts, da kuma waɗanda suke daga saman Layer - keratinocytes, suna daidaita kansu a cikin wannan tsari ko da bayan an girma a cikin dakin gwaje-gwaje da kuma yin aikin fesa ta hanyar na'urar inji. Don iliminmu, mu ne rukuni na farko da ya ba da rahoton cewa fesa-akan ƙwayoyin fata suna da yuwuwar dawo da fata da aka ji rauni ta hanyar tsara tsarin gine-ginen fata na asali (epithelial stratification).

Na biyu, mun kuma koyi cewa ƙananan ƙira sun haifar da ƙalubale daban-daban don gwada ƙwayoyin feshi a kan ƙananan ƙananan wuraren rauni tare da ɓangarorin 'zamewa' lokacin da aka shafa. Waɗannan darussa masu mahimmanci sun ba mu ilimi da ƙwarewa mai ƙima don samun damar tsara jerin gwaje-gwaje na gaba waɗanda za su kusantar da mu ga gwaji a cikin ɗan adam. Misali, kawancenmu na dogon lokaci tare da Renovacare (wanda ya mallaki na'urar feshi) da kuma abokan aikinmu na ilimi a Paris da Madrid, za su ba mu, a matsayin mataki na gaba, don gwada kwayoyin feshin-kan da tantanin halitta. hanyoyin kwantar da hankali a cikin manyan samfuran kuma a cikin mutane, bi da bi.

Muna sa ran ci gaba da ci gabanmu zuwa fassarar asibiti na maganin fesa-kan kwayoyin halitta/cell don EB. (Daga rahoton ƙarshe na Janairu 2023.)