Imiphumela Yokuthoma Ezidakamizwa Ezihlose CGRP kanye Nomamukeli Walo
I-peptide ehlobene negciwane le-Calcitonin (i-CGRP), amaprotheni akhiqizwa ngamangqamuzana athile wegazi emzimbeni wesimiso esiyisisekelo kanye nesistimu yezinzwa ze-peripheral, kukholelwa ukuthi idlala indima ebalulekile kwimigraines. Akukona nje ukuthi le phrotheni itholakele phezulu ngesikhathi sokuhlasela kwe-migraine, kodwa ukunciphisa ubuhlungu be-migraine nemithi ye-migraine ebizwa ngokuthi i- triptan ihambisane nokujwayelekile kwamazinga e-CGRP egazini legazi.
Ngesikhathi sokuhlasela kwe-migraine, kungenzeka ukuthi ezinye izimbangela ze-migraine zivuselela izitsha zegazi ezungeze ubuchopho ukuze zihlanza, noma zikhulise. Lezi zingxube zegazi ezihlanjululwayo bese zivuselela izintambo zezintambo ezinama-trigeminal. Uma sekusetshenziselwe, i-trigeminal nerve fibers ithumela impendulo ebuhlungu ebuchosheni - okuholela ekukhululweni kwamaprotheni ahlukahlukene, afana ne-CGRP.
I-CGRP ibangela ukuthi kuqhutshekwe ukuqhutshwa kwemithambo yegazi kanye nokunye okubizwa ngokuthi "ukuvuvukala kwe-neurogenic". Njengoba ukuhlasela kwe-migraine kuqhubeka, i-brainstem iyancipha. Lokhu kuholela kumjikelezo ononya wobuhlungu bekhanda nokuzwela okukhulu kwendawo.
Yini Ucwaningo Lokuqala Lwama-CGRP?
Ucwaningo lwesiGaba II - izifundo ezenziwe ngenani elincane leziguli ukuze zithole inzuzo nemiphumela emibi yomuthi - kuze kube manje zithembisa ukuthi izifo zomzimba ze-CGRP zombili zivimbela i-migraines futhi zibekezelela kahle.
Kwesinye isifundo, abathintekayo abangu-217 abanama-4 kuya kwangu-14 abahamba ngezinyanga ngenyanga, bekungenangqondo ukuthola ngaphansi kwezigameko zesikhumba kabili ngesonto noma noma yiliphi ibizo elibizwa ngokuthi i-LY2951742 noma i-placebo - ishukela noma umjovo wamanzi - amasonto angu-12.
(LY2951742 i-antibody kuya kwe-peptide ehlobene ne-calcitonin ye-gene (CGRP) - lokhu kusho ukuthi ibophezela ku-CGRP futhi ibimbela noma ayivimbeli).
Imiphumela iphakamise ukuthi ababambiqhaza abathola i-LY2951742 babe nokunciphisa okukhulu kwenani lezinsuku zekhanda laso le-migraine uma kuqhathaniswa ne-placebo. Izindaba ezinhle futhi ukuthi le mithi itholakala ukuthi iphephile futhi ibekezelelwe kahle yizihloko.
Lokhu kuthiwa imiphumela emibi yayihlanganisa:
- injection site injection
- ubuhlungu besisu
- ukutheleleka okuphezulu kokuphefumula (isib. i-bronchitis)
Esinye isidakamizwa esibizwa ngokuthi i-ALD403 - futhi i-peptide antibody ehlobene ne-calcitonin-ihlolwe kwabahlanganyeli abangu-163 abanama-5 kuya ku-14 abahamba ngezinyanga. Ingxenye eyodwa yalezi zihloko zamukelwe ngempumputhe ingu-1000mg enomdlavuza (nge-vein) umthamo wesidakamizwa, kanti enye ingxenye yathola i-placebo. Izihloko zalandelwa izinyanga ezingu-6.
Phakathi namasonto 5 kuya ku-8, abahlanganyeli abathola izidakamizwa babona ukuncipha kwamaphesenti angama-66 kwinani lezinsuku abahlupheke ngamaphesenti angu-52 kuya kwezingu-52 kulabo abathola indawo ye-placebo.
Futhi, emasontweni angu-12, amaphesenti angu-16 weziguli ezathola lesi sidakamizwa ayengenasiphelo sama-migraine ngokuphelele ngaphandle kwalabo abathola i-placebo.
Okokugcina, omunye umuthi, olawulwa ngaphansi kwesikhumba (injection engaphansi) ebizwa ngokuthi i-AMG 334 - i-antibody ebophezela kumamukeli we-CGRP (isayithi lokuzivocavoca le-CGRP) - lisanda kutholakala ukuvimbela imishanguzo. Njengezinye izidakamizwa ezimbili, i-AMG 334 yayinakekelwa kahle. Imiphumela emibi kakhulu evamile yilezi:
- izimpawu ezibandayo
- ukukhathala
- ikhanda noma i-migraine (hamba isibalo - sincane kakhulu, amaphesenti angu-3 aphikisana namaphesenti angu-1 eqenjini le-placebo)
- isiyaluyalu
- ukutheleleka okuphezulu kokuphefumula (isib. i-bronchitis).
Okubalulekile
Ngempela lezi ziphumo ezijabulisayo zomphakathi we-migraine. Noma kunjalo, ucwaningo lwesigaba se-III olukhudlwana futhi lukhulu futhi luqinisekisa izimangalo zezifundo zesigaba II - kufanele zenziwe ngaphambi kokuba lezi zidakamizwa zitholakale ezigulini.
Imithombo:
I-Bigal ME, i-Walter S, i-Rapoport AM. I-peptide ebika i-Calcitonin yegesi (CGRP) nokuqonda kwe-migraine yamanje kanye nesimo sokuthuthukiswa. Izinwele . 2013; 53 (8): 1230-44.
I-Durham PL. I-Calcitonin i-Peptide ehlobene ne-Gene (CGRP) ne-Migraine. Izinwele. 2006; 46 (Suppl 1): S3-S8.
I-Goadsby PJ, ne-Edvinsson L. Uhlelo lwe-trigeminovascular kanye ne-migraine: izifundo ezibonisa ukuguquka kwe-cerebrovascular ne-neuropeptide ebonakala kubantu namakati. Ann Neurol. 1993 Jan; 33 (1): 48-56.
Imiphumela yokuqala ye-ALD403, Umuthi Omusha Wokuphenya for Prevention Migraine. (nd). E-American Headache Society. Ibuyiselwe ngo-May 18, 2014.
Sun H et al. Ukuphepha nokusebenza kwe-AMG 334 ekuvimbeleni i-epradic migraine: ukuhlolwa kwe-phasebo okulawulwa ngokungahleliwe, okubili okuyimpumputhe, okuyi-doublebofu. I-Lancet Neurol. 2016; 15 (4): 382-90.