Kuchiza DEB itch ndi ma stem cell (2022)

Magulu atatu a anthu adachita nawo kafukufuku wa PRUMEC: anthu omwe ali ndi DEB-pruriginosa, ndi magulu awiri a 'control': anthu omwe ali ndi DEB (osati pruriginosa) ndi odzipereka opanda EB.

Zotsatira za kuyerekeza zitsanzo za khungu ndi magazi kuchokera m'magulu atatuwa zimasonyeza kuti mayankho a chitetezo cha mthupi (kutupa) pakhungu, osati m'magazi, ndi omwe amachititsa kuyabwa. Kutupa kumeneku kunali kwa mitundu iwiri yofunika kwambiri, imodzi yokhudzana ndi chikanga ndi ina yokhudzana ndi psoriasis, kutanthauza kuti mankhwala amtunduwu akhoza kubwezeretsedwanso bwino kuti athetse EB itch.

Ofufuzawa akukonzekera kuchita mayesero a zachipatala kuti apereke umboni wakuti mankhwalawa amagwira ntchito ku EB kotero kuti, m'tsogolomu, akhoza kukhala ndi chilolezo ndikugwiritsidwa ntchito nthawi zonse kuti apititse patsogolo moyo wa EB.

Ofufuza adasindikiza ndemanga m'magazini ya British Association of Dermatology mu 2021 komanso zotsatira zina munkhani yotchedwa "Mbiri ya Transcriptomic ya recessive dystrophic epidermolysis bullosa khungu lovulala likuwonetsa mwayi wogwiritsanso ntchito mankhwala kuti apititse patsogolo kuchira.".

Atsogoleri Ofufuza:
Prof John McGrath MD FRCP FMedSci ndi Pulofesa wa Molecular Dermatology pa King's College London komanso Mtsogoleri wa Genetic Skin Disease Unit, komanso Head Consultant Dermatologist ku St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust ku London. M'mbuyomu anali mnzake wofufuza za EB wothandizidwa ndi DEBRA ndipo wagwira ntchito pa kafukufuku wa EB kwa zaka zopitilira 25. Tsopano amatsogolera ndikugwirizanitsa ntchito zingapo za National and International kuti apange jini, maselo, mapuloteni ndi mankhwala ochiritsira omwe angapangitse chithandizo chabwino kwa anthu omwe ali ndi EB.

Prof Jemima Mellerio ndi Consultant Dermatologist komanso pulofesa ku St John's Institute of Dermatology, Guy's ndi St Thomas' NHS Foundation Trust. Ali ndi zaka zoposa 20 akugwira ntchito zachipatala m'munda wa EB ndi matenda ena a khungu lachibadwa, komanso kafukufuku wofufuza momwe maselo amitundu yosiyanasiyana a EB amakhalira, komanso mayesero azachipatala kukhala mankhwala atsopano a EB monga fibroblast ndi mesenchymal stromal cell. chithandizo. Amadzipereka kupitiliza ntchitoyi kuti apange chithandizo chamankhwala chamitundu yonse ya EB.

"Chizindikiro chimodzi chovutitsa kwambiri mwa anthu omwe ali ndi EB ndi kuyabwa. Pakadali pano, sitikudziwa zomwe zimayambitsa kuyabwa komanso zocheperako momwe tingachitire. Ndife okondwa kulandira ndalama za DEBRA kuti tigwiritse ntchito itch. Tikhala tikuphunzira anthu omwe ali ndi mtundu woyabwa kwambiri wa EB wotchedwa EB pruriginosa. Tikukonzekeranso kuyesa kuyesa ma cell a m'mafupa omwe tikukhulupirira kuti achepetsa kuyabwa ndikuwongolera khungu la EB. "

Prof John McGrath

Mutu wa Grant: Kuwunika kwamphamvu koyambirira kwa ma cell a allogeneic mesenchymal stromal omwe amalowetsedwa m'mitsempha pa kuyabwa mwa akulu omwe ali ndi epidermolysis bullosa Pruriginosa (PRUMEC - PRUSTEM).

Ndalama zofufuzirazi zagawidwa m'magawo awiri - PRUMEC ndi PRUSTEM.
Gawo 1 - PRUMEC Case-control mechanistic study of pruritus (itch) mwa akuluakulu omwe ali ndi dystrophic epidermolysis bullosa pruriginosa.
Gawo 2 - PRUSTEM - Kuunikira koyambirira kwa ma cell a allogeneic mesenchymal stromal omwe amalowetsedwa m'mitsempha mwa akulu omwe ali ndi epidermolysis bullosa Pruriginosa.

Kudalirika
Kafukufukuyu ndi wokhudza kuyabwa mu epidermolysis bullosa (EB). Tikudziwa kuti kuyabwa ndi chizindikiro chofala komanso chovutitsa maganizo, ndikuti kuwongolera bwino kuyabwa ndikofunikira kwambiri pakufufuza kwa anthu omwe ali ndi EB. Pakadali pano, sizikumveka chifukwa chake khungu limayabwa mu EB ndipo tikudziwa kuti mankhwala ambiri omwe alipo siwothandiza kwenikweni.
Mayesero am'mbuyomu amtundu wa chithandizo cha ma cell adatenga ma cell a m'mafupa (maselo a mesenchymal stromal, MSCs) kuchokera kwa opereka athanzi osagwirizana ndikuwalowetsa kudzera mumtsempha mwa ana ndi akulu omwe ali ndi recessive dystrophic EB; mayeserowa amatchedwa EBSTEM ndi ADSTEM ndipo anasonyeza kuti maselo anali otetezeka komanso kuti mwa anthu ambiri kulowetsedwa kwa selo kunali ndi ubwino wochiritsa mabala, kupweteka kwa khungu ndi kuyabwa.

Pulojekitiyi idzafufuza njira zomwe zikugwiritsidwa ntchito ndi chithandizo cha itch mu EB chidzagawidwa mu magawo awiri, PRUMEC ndi PRUSTEM.

Gawo 1 - PRUMEC

Ichi ndi phunziro loyang'anira zochitika, (mtundu wa kafukufuku wowonetsetsa wokhudza 2 kapena magulu ambiri) omwe cholinga chake ndi kudziwa ngati magulu ali ndi zotsatira zosiyana pambuyo pa phunzirolo. Popeza uku ndi kafukufuku wamakina, izi zikutanthauza kuti kafukufukuyu akufuna kumvetsetsa momwe zamoyo zimakhalira kumbuyo kwa pruritus (kuyabwa) ndikuzindikira zomwe mukufuna kulandira.
Popeza kafukufukuyu akuphatikiza kuphunzira njira zomwe zimayambitsa pruritus, padzakhala magulu atatu osiyana:

1. Akuluakulu a 10-30 omwe ali ndi dystrophic epidermolysis bullosa pruriginosa (DEB-P), omwe amatengedwa ndi zitsanzo zapakhungu ndi magazi poyerekeza ndi,
2. 10-30 akuluakulu omwe ali ndi DEB non-pruriginosa subtype (DEB-NP), ndi
3. 10-30 odzipereka athanzi ngati magulu owongolera.

Odwala olembedwa adzafanana ngati n'kotheka, mofanana ndi zomwe zingatheke pachipatala komanso momwe zingathere, malinga ndi msinkhu, jenda, mtundu, kuuma kwa EB, nthawi ya biopsy ndi malo a biopsy. Mafunso komanso zitsanzo za magazi ndi khungu zidzatengedwa kuchokera ku gulu lirilonse kwa miyezi 12. Izi zidzalola kufananitsa pakati pa magulu.

Gawo 2 - PRUSTEM (Mayesero a Gawo I/II)

Gawoli lidzatsatira kukwaniritsidwa kwa PRUMEC, pomwe gulu laling'ono la odwala DEB-P omwe adalembetsa adzapatsidwa mankhwala malinga ndi zotsatira za PRUMEC. Kuyeza magazi, mafunso ndi ma biopsies zidzabwerezedwa ndikuchitidwa monga momwe zinaliri mu kafukufuku wa PRUMEC ndikuyerekeza ndi zoyambira zomwe zidachitika mu gawo loyamba.

Mankhwalawa adzakhala ngati chithandizo cha ma cell pomwe mpaka akulu akulu 10 omwe ali ndi EB pruriginosa aliyense adzalandira 3 kulowetsedwa kwa MSCs. Ntchitoyi idzayesa kuyabwa pogwiritsa ntchito njira yowerengera mwatsatanetsatane yotchedwa Leuven Itch Scale, yomwe idayesedwa kale mu EB. Khungu ndi magazi zidzawunikidwa pambuyo poti chithandizo cha maselo chikaperekedwa kuti afufuze momwe maselo angagwiritsire ntchito kuchepetsa kuyabwa ndikuyerekeza ndi zotsatira zomwe zidatengedwa kale.

Zotsatira zidzafanizidwanso ndi magazi a anthu a 10 omwe ali ndi DEB - NP ndi maphunziro a 10 omwe alibe EB kuchokera ku phunziro la PRUMEC. Anthuwo sangalandire chithandizo cha ma cell a MSC, koma zitsanzo zawo zitha kukhala zothandiza poyesa kudziwa chomwe chimayambitsa kuyabwa kwa EB pruriginosa poyamba.

Cholinga chonse cha ntchitoyi ndikuwongolera kumvetsetsa za (a) zomwe zimayambitsa kuyabwa mu EB pruriginosa (ndi mitundu ina ya EB), (b) ngati kulowetsedwa m'mitsempha ya MSCs kumapereka chithandizo chothandizira kwa anthu omwe ali ndi EB pruriginosa ndi, (c) ) momwe ma MSC amagwira ntchito pochepetsa kuyabwa mu EB pruriginosa. Tikuyembekeza kuti zotsatira zophatikizana za EBSTEM, ADSTEM ndi PRUSTEM/PRUMEC zidzafotokozera ubwino wa mtundu uwu wa chithandizo cha maselo kwa anthu omwe ali ndi DEB (ndi mitundu ina ya EB) ndikupereka chilimbikitso pa chitukuko cha MSC cell therapy monga gawo. za chisamaliro chanthawi zonse cha DEB.

PRUMEC: Kafukufuku wamakina owongolera a pruritus mwa akulu omwe ali ndi dystrophic epidermolysis bullosa pruriginosa.

Itch ndi imodzi mwazovuta kwambiri za anthu omwe ali ndi epidermolysis bullosa (EB). Ndizofala kwambiri komanso zovuta kwambiri mu dystrophic subtype ya EB (DEB). Pakhala pali kafukufuku wambiri wokhudza njira zoyabwa m'mikhalidwe yakhungu m'zaka makumi awiri zapitazi, zomwe zawonjezera kumvetsetsa kwathu kotero kuti titha kupanga chithandizo chothandizira. Komabe, kuyabwa mu DEB sikunaphunzirepo pamlingo womwewo ndipo koposa zonse, mankhwala omwe atha kuchepetsa kapena kuyimitsa bwino sapezeka ku gulu ili. Chifukwa chake tidapanga kafukufuku wofufuza, ndicholinga chofuna kudziwa chomwe chimayambitsa kuyabwa mumtundu wa DEB woyabwa kwambiri, wotchedwa pruriginosa. Cholinga chathu chachikulu chinali kuzindikira njira zomwe titha kulunjika ndikutsekereza ndi mankhwala, kuti tichepetse kuyabwa.

Pa kafukufukuyu, tidalemba anthu m'magulu atatu: anthu omwe ali ndi DEB pruriginosa (DEB-P), pamodzi ndi magulu awiri 'olamulira' a anthu omwe ali ndi DEB opanda khungu loyabwa komanso opanda khungu kapena matenda ena (odzipereka athanzi, HV) . Ophunzira m'magulu olamulira adafanana ndi omwe adatenga nawo gawo la DEB-P momwe angathere kwa zaka, jenda ndi fuko, kuti titsimikizire kuti kusiyana komwe kumawoneka pakati pa magulu panthawi yoyesera sikunayambe chifukwa cha kusiyana pakati pa magawo awa pakati pawo. magulu. Aliyense adamaliza maulendo 2-3 ofufuza nafe. Pazimenezi, tidayesa kuopsa kwa EB ndi kukula kwake m'magulu awiri a DEB pogwiritsa ntchito mphambu yomwe imadziwika kuti EBDASI ndipo tinapempha otenga nawo gawo ku DEB kuti amalize mafunso okhudza momwe EB imakhudzira moyo wawo (QoL). Otenga nawo gawo pa DEB-P adamalizanso masikelo awiri ovomerezeka omwe amawunika mawonekedwe a kuyabwa, monga kuuma, pafupipafupi komanso nthawi yayitali, yotchedwa Leuven Itch Scale (LIS) ndi 5D sikelo. Tinatenga zitsanzo za magazi kuchokera kwa onse otenga nawo mbali ndi ma biopsies a khungu kuchokera kwa omwe anali okondwa kuti titero. Kuyezetsa magazi kunkachitidwa m'magazi kuti ayese zizindikiro za kutupa ndikuwonetsetsa kuti otenga nawo mbali alibe mavuto ena omwe angayambitse kuyabwa, monga kusokonezeka kwa atopy, chiwindi kapena impso. Zitsanzo zapakhungu kuchokera kwa omwe adatenga nawo gawo la DEB-P ndi DEB-NP adatengedwa kuchokera kumadera onse okhudzidwa (otupa) komanso osakhudzidwa (osakhala a lesional).

Kenako tinayesa kambirimbiri magazi ndi khungu kuti tidziwe kuchuluka kwa majini ndi mapuloteni. Magawo awa adafanizidwa pakati pa DEB-P ndi magulu awiri olamulira.

Malingaliro angapo adapangidwa potengera zotsatira.

Makamaka, zidadziwika mu kafukufukuyu kuti kwa anthu omwe ali ndi DEB-P kuyabwa kumangokhala pakhungu (lofiira, lotupa kapena lovulala). Izi ndizowona zomwe zikuwonetsa kuti palibe chomwe chimayambitsa kuyabwa, koma kuti njira zomwe zimayendetsa zimangokhala pakhungu, makamaka pakhungu.

Zolemba zotupa m'magazi zimasonyeza kuti pali kutupa kwakukulu pakhungu la DEB-P poyerekeza ndi DEB yosayabwa, monga momwe tingayamikire poyang'ana khungu ndi maso kapena pansi pa microscope.

Kuopsa kwa matenda ndi zotsatira za QoL zonse zikuwonjezeka mu DEB-P. Kuyabwa koopsa ndi komwe kumayambitsa izi, chifukwa kumakhudza kwambiri kugona kwa anthu, moyo wawo watsiku ndi tsiku komanso zochita za tsiku ndi tsiku, pomwe kukanda khungu kumayambitsa matuza ndi mabala atsopano.

Chosangalatsa ndichakuti kukula kwa kuyabwaku kunali kofanana ndi kuchuluka kwa zolembera zotupa m'magazi a anthu a DEB-P, kutanthauza ubale wolimba pakati pa kuyabwa ndi kutupa khungu. Izi zikutanthauza kuti ngati tiganizira kwambiri za kutupa kwa khungu la anthu omwe ali ndi DEB, zitha kutithandiza kumvetsetsa, ndikuchiza bwino.

Kusunthira kuzomwe zapezedwa pama cell ndi ma cell, maphunziro athu m'magazi adawonetsa kuti oyimira pakati pa kutupa samakwezedwa m'magazi a DEB-P poyerekeza ndi zowongolera. Izi zikutanthawuza kuti mwina zida zathu sizili zomveka bwino kuti zizindikire kusiyana komwe kulipo, kapena kuti kutupa kumangokhala pakhungu ndipo sikumadutsa pakuyenda kwambiri. Mogwirizana ndi izi, panalibe kusiyana kwakukulu kwa mayendedwe a jini m'magazi pakati pa magulu. Komabe, muyeso wathu wonse wa mapuloteni osiyanasiyana m'magazi udawonetsa kuti maselo amwazi omwe amadziwika kuti mapulateleti, omwe amakhudzidwa ndi mapangidwe amagazi amawumbidwa mu DEB-P poyerekeza ndi zowongolera zonse ziwiri. Chodabwitsa ichi komabe sichachindunji cha DEB-P ndipo chafotokozedwa m'mikhalidwe ina yomwe khungu limayaka komanso kuyabwa.

Zotsatira zofunika kwambiri za phunziroli zinachokera kuyerekeza khungu lokhudzidwa la DEB-P anthu omwe ali ndi khungu losakhudzidwa lomwe linatengedwa kuchokera kumadera oyandikana nawo mwa anthu omwewo, komanso ma biopsies ochokera kumalo omwewo otengedwa ku DEB-NP ndi HV. Choyamba, mawonekedwe a jini ndi mapuloteni mu khungu losakhudzidwa, losayabwa la anthu a DEB-P onse anali ofanana kwambiri ndi omwe ali ndi khungu lathanzi kuchokera ku DEB-NP ndi HV. Zinali pamene tinkayerekezera zotupa za khungu la DEB-P ndi khungu lowoneka bwino kuchokera ku DEB-P, DEB-NP ndi HV, kusiyana kunawoneka. Makamaka, njira zingapo zokhudzana ndi chitetezo chamthupi zinapezeka kuti ndizowonjezera kwambiri mu zilonda za DEB-P. Njira ziwiri zosiyana zinkawoneka kuti zimalamulira chitetezo cha mthupi pakhungu lawo,. Mamolekyu angapo amakhudzidwa ndi njira izi (kapena zotchedwa 'zotupa zotupa'), zina mwazomwe titha kuziletsa ndi m'badwo watsopano, mankhwala omwe amayang'aniridwa kwambiri omwe amadziwika kuti biologics. Mankhwalawa amagwiritsidwa ntchito kale pa chikanga ndi psoriasis pochita zachipatala ndipo amaonedwa kuti ndi otetezeka. Biologics sinakhale mbali ya chithandizo cha EB mwachizolowezi, komabe zotsatira za phunziroli zimatipatsa chifukwa chomveka chokhulupirira kuti zingakhale zothandiza kuchepetsa kutupa, choncho kuyabwa, pakhungu la anthu omwe ali ndi dystrophic EB. Mu gawo lotsatira la kafukufuku wathu, tikukonzekera mayesero azachipatala komwe tidzayesa ena mwa othandizirawa mu DEB. Tikukhulupirira kuti tipanga umboni womwe utiloleza kuti mankhwalawa azipezeka pafupipafupi kwa anthu omwe ali ndi DEB m'chipatala. (Kuchokera ku lipoti lomaliza la 2022.)