1kits (Ebipipa 10) .
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▎ Okukubaganya ebirowoozo ku Cagrilintide
Cagrilintide ye dual amylin ne calcitonin receptor agonist (DACRA) nga ya yinginiya okusinziira ku nsengeka y’ensengekera ya amylin. Kikola nga kikola byombi ekikwata amylin n’ekikwata calcitonin, bwe kityo ne kiraga obusobozi okukyusakyusa mu nkyukakyuka y’emmere, omuli obuzito bw’omubiri n’emiwendo gya glucose mu musaayi.Enkula ya Cagrilintide yeesigamiziddwa ku nkola z’omubiri eza amylin enzaaliranwa. Amylin, obusimu obufulumizibwa obutoffaali bw’olubuto, bukola kinene nnyo mu kuleetera omuntu okukkuta, oluvannyuma ekivaako okukendeeza ku mmere gy’olya. Ate era, amylin eyamba mu kulungamya enkyukakyuka ya glucose mu musaayi okuyita mu nkola eziwera, gamba ng’okuziyiza okufulumya glucagon oluvannyuma lw’okulya n’okulwawo okufulumya amazzi mu lubuto.Not with standing its physiological significance, native amylin is limited in clinical application due to its relatively short half-life. Okusobola okukola ku buzibu buno, Cagrilintide ekoleddwa nga analog ekola ebbanga eddene, ng’erina ekitundu ky’obulamu bwa nnaku nga 7 ku 8. Ekitundu kino eky’obulamu obwongezeddwayo naddala kyongera ku bulungibwansi bw’okugaba n’okugoberera omulwadde, nga kiwa enkola ey’obujjanjabi ey’omugaso ennyo.
▎ Enzimba ya Cagrilintide
Ensibuko: PubChem |
Omutendera: Pyr-KCNTATCATQRLAEFLRHSSNNFGPILPPTNVGSNTP CAS: 1415456-99-3 ku ssimu Ensengekera: C 174H 269N 45O 52S2 MW 4409 g/mol |
▎ Okunoonyereza ku Cagrilintide
Ensibuko ya Cagrilintide eri etya?
Cagrilintide —ekirungo ekifaanagana ne amylin:
Amylin ye hormone efulumizibwa obutoffaali bwa pancreatic islet β. Mu mbeera z’omubiri, ekolagana ne insulini era erina emirimu mingi egy’amaanyi egy’omubiri.
Ekisooka, amylin akola kinene nnyo mu kuleeta okukkuta n’okukendeeza ku mmere gye balya. Enkola yaayo ey’okukola okusinga erimu okukola ku bikwata mu Area Postrema ku musingi gw’ekisenge eky’okuna. Obubonero bw’obusimu buyisibwa mu bwongo obw’omu maaso nga buyita mu Nucleus of the Solitary Tract. Mu kiseera kye kimu, era zisobola okutuusibwa mu kitundu kya Lateral Hypothalamic Area n’ebibinja ebirala ebya nyukiliya ebya hypothalamic nga biyita mu Lateral Parabrachial Nucleus. Amylin alina obusobozi okusitula ekifo ekikuta ky’ekiramu n’okuziyiza okulya emmere mu bisolo [1] ..
Amylin asobola okulungamya glucose homeostasis, ekituukibwako nga kiziyiza okufulumya insulin ne glucagon byombi [2] . Omulimu guno guyamba nnyo mu kukuuma omutindo gwa glucose mu musaayi nga gutebenkedde era gulina obukulu bungi mu kujjanjaba endwadde nga sukaali.
Ate era, amylin ekola ebikolwa byayo ng’ekwata ku kufulumya obusimu obutambuza obusimu. Okugeza, kiziyiza okufulumya dopamine mu hypothalamus y’envunza, ate nga kirina akakwate katono ku norepinephrine ne serotonin [3] . Mu mbeera ya glucose homeostasis, amylin ekuuma obutebenkevu bwa glucose mu musaayi ng’anyigiriza okufulumya kwa insulin ne glucagon. Enkola zaayo mulimu okukola butereevu ku butoffaali bwa pancreatic islet α n’okulung’amya mu ngeri etali butereevu okufuluma kwa glucagon okuyita mu kukyusa obubonero bw’obusimu mu hypothalamus. Mu balwadde ba ssukaali, okusaanawo kw’obutoffaali bwa β tekikoma ku kuleeta bbula lya insulini wabula era kivaamu okukendeera kw’okufulumya kwa C-peptide ne amylin zombi. Amylin kirabika yeenyigira mu kulungamya glucose homeostasis nga eziyiza okufulumya mu lubuto n’okukola glucose mu kibumba oluvannyuma lw’okulya, okukkakkana ng’akendeeza ku nkyukakyuka za glucose mu musaayi oluvannyuma lw’okulya [4] . Okugatta ku ekyo, amylin esobola okulwawo okufulumya amazzi mu lubuto, okuziyiza okuzimba olubuto okuyita mu busimu obw’omu makkati, n’okuwangaaza obudde emmere gy’emala mu nkola y’olubuto, bwe kityo n’alemesa glucose okweyongera amangu mu musaayi.
Wadde kiri kityo, amylin erina ekitundu ky’obulamu ekitono ennyo, ekiziyiza okukozesebwa kwayo mu bujjanjabi. Okunoonyereza kulaga nti eddagala eririwo erya amylin analog, pramlintide, ng’eddagala eriyamba mu kujjanjaba ssukaali, lyetaaga okuweebwa emirundi esatu olunaku. Kino tekikoma ku kuleeta buzibu eri balwadde wabula era kikendeeza ku kugoberera kwabwe [5] . Okusobola okukola ku nsonga y’ekitundu ky’obulamu obutono obwa amylin ow’obutonde, Cagrilintide ekoleddwa nga analog ekola okumala ebbanga eddene. Enkula ya Cagrilintide yeesigamiziddwa ku kutegeera okw’amaanyi ku mirimu gy’omubiri egya amylin ow’obutonde. Kigenderera okukoppa enkola y’okukola kwa amylin ate nga kyongera ku bunywevu n’okukola okumala ebbanga eddene eby’eddagala lino okusobola okutuukiriza ebyetaago by’obujjanjabi obw’obujjanjabi.
Ebintu Ebisoboka n’Eddagala lya Cagrilintide
Cagrilintide ye novel long-acting amylin analogue nga erina obusobozi obw’amaanyi, eraga ebikolwa ebyewuunyisa mu kujjanjaba omugejjo ne sukaali. Kirimu amasavu era kirina engeri ezitebenkedde ezikola okumala ebbanga eddene [5] . Amylin ye hormone efulumizibwa wamu obutoffaali bwa pancreatic β wamu ne insulin, ereetera okukkuta nga ekola ku bitundu by’obwongo ebiyitibwa homeostatic ne hedonic. Nga analogue ya amylin, Cagrilintide esobola okukoppa ekikolwa kino, okuleeta okukkuta era bwe kityo n’ayamba mu kufuga obuzito. Ekirala, Cagrilintide ye dual amylin ne calcitonin receptor agonist, eggibwa mu mugongo gwa amylin, ekigiwa enkola ey’enjawulo ey’okukola mu kulungamya metabolic.
Enkulaakulana y’okunoonyereza ku bujjanjabi ku Cagrilintide
Mu kugezesebwa mu malwaliro, Cagrilintide evuddemu ebisuubiza mu kuleeta okugejja. Okugeza, mu kugezesebwa okw’okuzuula ddoozi okw’omutendera ogw’okubiri, okwakolebwa mu bifo ebingi, okwakolebwa mu ngeri ey’ekifuulannenge, okwakolebwa mu bifo bibiri, okwafugibwa placebo, n’okufugibwa active-controlled phase 2 dose-finding trial, abeetabye mu kugezesebwa okwajjanjabwa ne Cagrilintide baalaga okugejja okusinga okweyoleka bw’ogeraageranya n’abo abaafuna placebo. Ebitundu ku kikumi eby’okukendeeza ku buzito okuva ku ntandikwa ku ddoozi zonna eza Cagrilintide (0.3 - 4.5 mg) byali bingi (6.0% - 10.8%) okusinga eby’ekibinja kya placebo (3.0%). Okukendeera kw’obuzito mu kibinja ekyajjanjabwa ne 4.5 mg za Cagrilintide nakyo kyali kinene okusinga mu kibinja ekyajjanjabwa ne 3.0 mg ya liraglutide (10.8% vs. 9.0%). Ebivudde mu kunoonyereza kuno biraga nti Cagrilintide esobola okuba enkola ennungi mu kuddukanya obuzito [6]..
Cagrilintide ne GLP-1 receptor agonist semaglutide zirina enkola ez’enjawulo naye nga zikwatagana. Semaglutid ekola ebikolwa byayo ng’ekola ku bikwata GLP-1 mu hypothalamus, ekivaako okukendeeza ku njagala y’okulya, okweyongera mu kufulumya insulini, n’okulwawo okufulumya amazzi mu lubuto. Okwawukana ku ekyo, Cagrilintide eyongera okuziyiza okwagala okulya ng’ekola ebirungo ebikwata amylin. Okugaba ebirungo bino ebibiri okugatta kuleeta ekikolwa ekisukkiridde ku njagala y’okulya okuyita mu nkola eziwera, okutumbula ennyo obusobozi bw’okugejja [7] . Okusinziira ku butonde obuzibu obw’omugejjo, obujjanjabi obw’omugatte obugenderera enkomerero eziwera ez’obulwadde bukiikirira enkola entegeerevu era ennungi.
Ekirala, Cagrilintide era eraga obusobozi obusuubiza okufuga glucose mu musaayi mu balwadde ba sukaali ow’ekika eky’okubiri. Okunoonyereza mu bujjanjabi kulaga nti Cagrilintide eraga okutebenkera okulungi n’obulungi mu kuddukanya omugejjo n’obulwadde bwa sukaali obw’ekika eky’okubiri. Okugeza, mu kugezesebwa okwakolebwa mu malwaliro okwali kuzingiramu abalwadde ba sukaali ow’ekika eky’okubiri, okugatta Cagrilintide ne GLP-1 receptor agonist semaglutide kwalaga ebikolwa ebyewuunyisa eby’okufuga glucose mu musaayi n’okugejja. Kino kiraga nti Cagrilintide ekuuma omutindo gwa waggulu ogw’obutebenkevu mu nkola y’obujjanjabi era esobola okukola ebikolwa eby’obujjanjabi ebiwangaala. Mu kugezesebwa okulala, Cagrilintide, oba yaweebwa yokka oba nga egattibwa wamu ne semaglutide, yalaga okugumira obulungi n’obukuumi [8] . Kino kyongera okukakasa obutebenkevu bwa Cagrilintide, nga mu kukozesebwa mu bujjanjabi, okutebenkera kw’eddagala kukwatagana nnyo n’okugumiikiriza n’obukuumi bwalyo.
N’ekisembayo, mu kugezesebwa mu malwaliro, obujjanjabi obwa cagrilintide bugumiikiriza bulungi. Mu kugezesebwa okw’okuzuula ddoozi okw’omutendera ogw’okubiri, emiwendo gy’okuyimiriza obujjanjabi obw’olubeerera gyali gigeraageranyizibwa mu bibinja by’obujjanjabi eby’enjawulo, okusinga nga biva ku bizibu ebibaawo. Wadde kyali kityo, ebizibu ebisinga okubeerawo byali buzibu mu lubuto n’engeri gye baamukubamu empiso, ng’ebisinga obungi byali bitono oba bya kigero mu buzibu. Mu kugezesebwa okwa randomized, controlled phase 1b, obujjanjabi obw’omu kiseera kye kimu ne cagrilintide ne 2.4 mg za semaglutide era bwalaga okugumiikiriza okulungi n’obukuumi obukkirizibwa [9]. Okugezesebwa okunene n’okumala ebbanga eddene kyetaagisa mu biseera eby’omu maaso okwekenneenya mu bujjuvu obulungi n’obukuumi bw’obujjanjabi buno obw’omugatte.

Enkola y’enzimba ya Cagrinlintide
Ensibuko:PubMed [5] .
Amakulu g’okukozesa eddagala lya Cagrilintide
Okujja kwa Cagrilintide kuleese essuubi eppya mu kujjanjaba omugejjo ne sukaali ow’ekika eky’okubiri. Wadde ng’ekizibu ky’omugejjo mu nsi yonna kyeyongera okuba eky’amaanyi, enkola ezikkirizibwa mu kiseera kino ez’obujjanjabi obw’eddagala zikyali ntono. Nga novel long-acting amylin analogue, Cagrilintide egaba enkola empya ey’obujjanjabi eri abalwadde abagejjulukuka naddala abo abalina okuddamu okubi mu kuyingirira mu bulamu era nga tebasaanira kulongoosebwa bariatric. Kituuka ku kuddukanya obuzito nga kiyita mu nkola ey’enjawulo ey’okukola, nga kiwa ebirowoozo ebipya n’enkola ez’okujjanjaba omugejjo, era kiyinza okwoleka obulungi n’obukuumi bw’ogeraageranya n’eddagala ery’ekinnansi eriweweeza ku mugejjo [7] . Ate era, ensonga ewangudde ey’okugatta Cagrilintide ne semaglutide (CagriSema) eraga nti obujjanjabi obw’omugatte obugenderera ebigendererwa ebingi eby’omubiri (pathophysiological targets) nkola nnungi ey’okutumbula okuddamu kw’obujjanjabi mu mugejjo [8] . Enkola eno ey’obujjanjabi ey’ebigendererwa ebingi tekoma ku kuwa nkola mpya ey’okuddukanya omugejjo naye era ereeta okulongoosa okw’amaanyi mu nkyukakyuka y’emmere eri abalwadde abalina ssukaali ow’ekika eky’okubiri.
Mu kumaliriza, nga novel long-acting amylin analogue, Cagrilintide erina obusobozi obw’ekitalo mu kugejja n’okufuga glucose mu musaayi. Ekola ekkubo ly’obubonero bw’okukkuta nga ekoppa ekikolwa kya amylin era n’etereeza enkyukakyuka mu mubiri nga dual receptor agonist. Okugezesebwa mu malwaliro kulaga nti Cagrilintide, oba ng’ekozesebwa yokka oba ng’egatta wamu ne semaglutide, esobola okukendeeza ennyo ku buzito bw’omubiri era egumiikiriza bulungi. Okugatta ku ekyo, era eraga obusobozi obulungi obw’okufuga glucose mu musaayi mu balwadde ba sukaali ow’ekika eky’okubiri, okuwa eky’okulonda ekipya eky’okujjanjaba omugejjo ne sukaali n’okuziba ekituli mu nkola z’obujjanjabi eziriwo naddala eri abalwadde abo abataddamu bulungi ku bikolwa by’obulamu era abatasaanira kulongoosebwa. Enkola yaayo ey’obujjanjabi ey’ebigendererwa ebingi etuwa amagezi amapya ku nzirukanya y’endwadde z’enkyukakyuka mu mubiri.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Dr. DCW Lau pulofeesa mu ssomero ly’obusawo erya Cumming School of Medicine, mu yunivasite y’e Calgary mu Canada. Okunoonyereza kwe kukwata ku endocrinology ne metabolism, eddagala erya bulijjo n’ery’omunda, enkola y’emisuwa n’omutima, ebyobulamu by’abantu, ebyobulamu by’obutonde n’emirimu, wamu n’eby’obulwadde bwa kookolo. Era alina ebifo mu kkampuni ya Alberta Health Services (AHS) ne Obesity Canada era akolera mu kitongole ekinoonyereza ku ssukaali ekya Julia McFarlane. Dr. Lau alina obumanyirivu bungi mu kunoonyereza ku ssukaali n’omugejjo, ng’emirimu gye gifulumizibwa mu bitabo by’abayivu nga Canadian Journal of Diabetes. Dr. DCW awandiikiddwa mu kiwandiiko ekijuliziddwa mu kiwandiiko ekijuliziddwa [6].
▎ Ebiwandiiko Ebikwatagana
[1] Hansen KE, Murali S, Chaves IZ, Suen G, Ney D. M., ne bannaabwe abalala. Glycomacropeptide Ekwata ku Amylin-Mediated Satiety, Postprandial Markers of Glucose Homeostasis, ne Fecal Microbiome mu bakyala abagejjulukuka oluvannyuma lw’okuva mu nsonga. J NUTR 2023, era nga bwe kiri; 153 (7): 1915-29. DOI:10.1016/j.tjnut.2023.03.014.
[2] Ling W, Huang Y, Qiao Y, Zhang X, Zhao H. Amylin y’omuntu: Okuva ku bulwadde okutuuka ku by’omubiri n’eddagala. CURR PROTEIN PEPT SC 2019, eddagala eriweweeza ku bulwadde bwa ssennyiga; 20 (9): 944-57. DOI:10.2174/ 13892037206 66 19032811183 3. Enkola y’okukuuma obutonde bw’ensi.
[3] Brunetti L, Recinella L, Orlando G, Michelotto B, Di Nisio C, Vacca M. Ebikolwa bya ghrelin ne amylin ku kufulumya dopamine, norepinephrine ne serotonin mu hypothalamus. EUR J EDDAGALA 2002; 454 (2-3): 189-92. DOI:10.1016/S0014-2999 (02) 02552-9.
[4] Gedulin B. R., Jodka C. M., Herrmann K., Omuvubuka A. A.. Omulimu gwa endogenous amylin mu kufulumya glucagon n’okufulumya amazzi mu lubuto mu nvunza ogwalagibwa n’ekirungo ekiziyiza okulonda, AC187. Ebirungo ebiyitibwa Peptides ebifuga 2006; 137 (3): 121-7. DOI:10.1016/j.regpep.2006.06.004.
[5] Kruse T, Hansen JL, Dahl K, n’abalala. Enkulaakulana ya Cagrilintide, Amylin Analogue ekola ebbanga eddene. J MED CHEM 2021, eddagala eriweweeza ku bulwadde; 64 (15): 11183-94. DOI:10.1021/acs.jmedchem.1c00565.
[6] Lau DCW, Erichsen L, Francisco A. M., n’abalala. Cagrilintide omulundi gumu buli wiiki okuddukanya obuzito mu bantu abagejjulukuka n’omugejjo: okugezesebwa okwa multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. LANCET 2021 mu ssaza ly’e Mukono; 398 (10317): 2160-72. DOI:10.1016/S0140-6736 (21) 01751-7.
[7] D’Ascano A. M., Mullally J. A., Frishman W. H., ne bannaabwe abalala. Cagrilintide: Amylin Analog ekola ebbanga eddene mu kujjanjaba omugejjo. OMUTIMA REV 2024; 32 (1): 83-90. DOI:10.1097/CRD.0000000000000513.
[8] Frias JP, Deenadayalan S, Erichsen L, n’abalala. Obulung’amu n’obukuumi bwa cagrilintide 2.4 mg eweebwa awamu omulundi gumu buli wiiki ne semaglutide 2.4 mg omulundi gumu buli wiiki mu ssukaali ow’ekika eky’okubiri: okugezesebwa okwakolebwa mu bifo bingi, okwakolebwa mu ngeri ey’ekifuulannenge, okutali kwa maaso emirundi ebiri, okufugibwa okukola, okw’omutendera ogw’okubiri. LANCET 2023 mu mwaka gwa 2023; 402 (10403): 720-30. DOI:10.1016/S0140-6736 (23) 01163-7.
[9] Enebo LB, Berthelsen KK, Kankam M, n’abalala. Obukuumi, okugumiikiriza, enkola y’eddagala, n’enkola y’eddagala ey’okuweebwa awamu dose eziwera eza cagrilintide ne semaglutide 2.4 mg okuddukanya obuzito: okugezesebwa okutali kwa bulijjo, okufugibwa, okw’omutendera 1b. LANCET 2021 mu ssaza ly’e Mukono; 397 (10286): 1736-48. DOI:10.1016/S0140-6736 (21) 00845-X.
EBINTU BYONNNA N’AMAWULIRE GW’EBINTU EBIweereddwa KU MUTINDO GUNO BIKOZESEBWA KU KUSASANYA AMAWULIRE N’EBIKOLWA BY’OKUSOMESA.
Ebintu ebiweereddwa ku mukutu guno bigendereddwamu kunoonyereza mu kisenge (in vitro research) byokka. Okunoonyereza mu vitro (Olulattini: *mu ndabirwamu*, ekitegeeza mu bikozesebwa mu ndabirwamu) kukolebwa ebweru w’omubiri gw’omuntu. Ebintu bino si bya ddagala, tebikkiriziddwa kitongole kya Amerika ekivunaanyizibwa ku by’emmere n’eddagala (FDA), era tebirina kukozesebwa kuziyiza, kujjanjaba oba kuwonya mbeera yonna ya bujjanjabi, bulwadde oba bulwadde. Kikugirwa nnyo mu mateeka okuyingiza ebintu bino mu mubiri gw’omuntu oba ebisolo mu ngeri yonna.