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1kits (Ebipipa 10) .
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▎ ya Melanotan-1 Enzimba
Ensibuko: PubChem |
Omutendera: Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val Ensengekera ya molekyu: C 78H 111N 21O19 Obuzito bwa molekyu: 1646.8g/mol Ennamba ya CAS: 75921-69-6 PubChem CID: 16154396. Enkola y’okukuuma eddagala lino Ebigambo ebifaanagana: Afamelanotida; NDP-MSH |
▎ Okunoonyereza ku Melanotan-1
Kiki ekiva mu kunoonyereza ku Melanotan-1?
Melanotan-1 ye analog ey’obutonde eya α-melanocyte-stimulating hormone (α-MSH). α-MSH ekolebwa obutoffaali obw’enjawulo mu mubiri gw’omuntu era ekola kinene mu nkola z’omubiri nga langi. Okusobola okunoonyereza ku ngeri gye yakozesebwamu mu bintu eby’enjawulo, abanoonyereza baakola eddagala lya Melanotan-1. Okunoonyereza okw’obwegendereza ku α-MSH kwavaako okuzaalibwa kwa Melanotan-1. α-MSH emanyiddwa okukola omulimu omukulu mu kusitula okukola melanin, era Melanotan-1 yategekebwa okuba n’emirimu egy’amaanyi n’emirimu egy’enjawulo, gamba nga mu kulongoosa olususu n’ebiyinza okukuuma ekitangaala [1]. .
Melanotan-1 kye ki?
Melanotan-1 ye analog ekoleddwa mu busimu obusitula α-melanocyte. Nga yesibye ku MC1R ku melanocytes, esitula melanocytes okukola melanin. Eraze nti ekola bulungi mu kujjanjaba obulwadde bwa erythropoietic protoporphyria era era erina essuubi eriyinza okukozesebwa mu kujjanjaba endwadde endala ez’olususu.
Melanotan-1 alina engeri y’okukola ekiwangaala. Kiyinza okusitula obutasalako obusimu obuyitibwa melanocytes mu mubiri okukola melanin, bwe kityo ne kiwa obujjanjabi obw’ekiseera ekiwanvu. Bw’ogeraageranya n’enkola endala ezimu ez’obujjanjabi, Melanotan-1 tekyetaagisa kuginywa nnyo, ekikendeeza ku buzito bw’obujjanjabi ku balwadde. Mu kunoonyereza ku bujjanjabi, Melanotan-1 eraga nti obukuumi bulungi. Ebizibu ebitera okuvaamu mulimu okulumwa omutwe, okuziyira, okusiiyibwa n’ebirala, naye okutwalira awamu biba bitono era bisobola okuwona ng’oyita mu bujjanjabi obutuufu. Okugatta ku ekyo, Melanotan-1 erina obutwa butono eri ebitundu ebikulu ng’ekibumba n’ensigo, ekiwa omusingo ogutali gumu ogw’obukuumi mu kukozesebwa kwayo mu bujjanjabi.
Enkola ki entongole Melanotan-1 gy’eziyiza omusana okwonooneka?
Melanin mu lususu akola kinene mu kunyiga emisinde gya ultraviolet ne free radicals, bwe kityo n’ekuuma olususu obutakosebwa ultraviolet. Obusannyalazo bwa Ultraviolet busobola okuleeta enkyukakyuka mu buzaale bw’obutoffaali bw’olususu era nga gwe gusinga okuvaako kookolo w’olususu ow’enjawulo. Okubeerawo kwa melanin kuyinza okukendeeza ku kukwatibwa obutereevu emisinde gya ultraviolet mu butoffaali bw’olususu n’okukendeeza ku bulabe bw’enkyukakyuka mu buzaale. Oluvannyuma lw’olususu okukwatibwa emisinde gya ultraviolet, kijja kuleeta okweyongera mu mirimu gy’ebikwata obusimu ebisitula melanocyte, ekivaamu okweyongera kwa eumelanin mu epidermal melanocytes. Nga analog ya α-melanocyte-stimulating hormone, Melanotan-1 esobola okukoppa enkola eno n’okutumbula okukola melanin [2] . Nga eyongera ku melanin mu lususu, Melanotan-1 esobola okukendeeza ku kwonooneka obutereevu kw’emisinde gya ultraviolet eri obutoffaali bw’olususu. Okunoonyereza kulaga nti oluvannyuma lw’okukozesa eddagala lya Melanotan-1, olususu okugumira emisinde gya ultraviolet kweyongera, era n’okubeerawo kw’okwokya omusana kukendeera. Bw’ogeraageranya n’enkola z’ekinnansi ez’okusiiga enviiri ng’okusiiga enviiri mu musana n’okukozesa ebintu ebikolebwa mu kulongoosa, Melanotan-1 erina ebirungi eby’enjawulo. Okulongoosa omusana kyetaagisa okubeera mu musana okumala ebbanga eddene, ekiyinza okuvaako olususu okwokya omusana, okukaddiwa n’okwongera okufuna kookolo w’olususu. Okukozesa ebintu ebizimba enviiri kiyinza okuba n’obuzibu ng’okunyiiga kw’olususu n’okulumwa alergy okuva ku bitundu by’eddagala. Melanotan-1, ng’ayita mu mpiso wansi w’olususu, esobola okufuga obulungi okukola kwa melanin n’okukendeeza ku buzibu obuva ku lususu.
Enkola ki entongole ey’okukola kwa Melanotan-1 mu kujjanjaba obulwadde bwa vitiligo?
Okusitula okukola melanin: Melanotan-1 asobola okusitula melanocytes okukola melanin. Melanin kintu kikulu ekisalawo langi y’olususu. Mu balwadde abalina vitiligo, olw’obutoffaali obuyitibwa melanocytes obwonooneddwa oba obutali bwa bulijjo, ebitundu ebyeru birabika ku lususu. Melanotan-1 etumbula okukula n’okwawukana kwa melanocytes era eyongera ku kukola melanin nga ekola amakubo ag’enjawulo ag’obubonero [3]..
Okutereeza abaserikale b’omubiri: Vitiligo etwalibwa ng’obulwadde obuva ku busimu obuziyiza endwadde, ng’abaserikale b’omubiri balumba mu ngeri etaali ya bulijjo obutoffaali obuyitibwa melanocytes. Melanotan-1 ayinza okukola kinene mu kulungamya abaserikale b’omubiri n’okukendeeza ku kulumba obutoffaali obuyitibwa melanocytes. Kiyinza okutereeza enkola y’abaserikale b’omubiri nga kikwata ku nkola n’enkola y’obutoffaali bw’abaserikale b’omubiri, bwe kityo ne kiwummuza obubonero bw’obulwadde bwa vitiligo.
Antioxidant effect: Oxidative stress nayo ekola kinene mu pathogenesis ya vitiligo. Melanotan-1 eyinza okuba n’obusobozi obumu obw’okuziyiza obuwuka obuleeta obulwadde era n’okukendeeza ku kwonooneka kw’okunyigirizibwa kw’okwokya (oxidative stress) eri melanocytes. Kisobola okumalawo ebirungo ebiyitibwa free radicals, okukuuma melanocytes okuva mu kwonooneka kwa oxidative, n’okuyamba okukuuma enkola eya bulijjo eya melanocytes.
Biki ebikwata ku kunoonyereza ebiwagira ebikolwa ebitongole ebya Melanotan-1 mu kujjanjaba erythropoietic protoporphyria?
Erythropoietic protoporphyria (EPP) bulwadde bwa porphyrin obusikira mu nkyukakyuka y’emmere nga abalwadde bafuna obutwa obw’amaanyi obw’ekitangaala, ekikosa ennyo omutindo gw’obulamu bwabwe. Nga synthetic analog of α-melanocyte-stimulating hormone, Melanotan-1 erina bino wammanga ebikwata ku kunoonyereza okuwagira ebikolwa byayo ebitongole mu kujjanjaba EPP:
Okulongoosa okugumira ekitangaala: Mu kunoonyereza okungi mu bujjanjabi, Melanotan-1 ekakasiddwa okulongoosa okugumira ekitangaala kw’abalwadde ba EPP. Okugeza, mu kugezesebwa kwa Phase III CUV039, obujjanjabi ne Melanotan-1 bwalongoosa okugumira ekitangaala kw’abalwadde ba EPP. Bw’ogeraageranya n’eddagala eriyitibwa placebo, obujjanjabi ne Melanotan-1 bwasobozesa abalwadde okumala ebiseera bingi mu musana obutereevu awatali bulumi era ne byongera ku budde okutuusa obubonero obusooka obw’obutwa bw’ekitangaala obuva ku nsibuko y’ekitangaala etuukiridde bwe bwalabika [4]. .
Okulongoosa omutindo gw’obulamu: Okunoonyereza okungi kulaga nti obujjanjabi bwa Melanotan-1 busobola okulongoosa omutindo gw’obulamu bw’abalwadde ba EPP. Mu kugezesebwa okw’enjawulo, oluvannyuma lw’okufuna obujjanjabi bwa Melanotan-1, omutindo gw’obulamu bw’abalwadde gwekenneenyezebwa nga bakozesa ebibuuzo ebikakasibwa, era ebyavaamu byalaga okulongoosa mu mutindo gw’obulamu [4]..
Obukuumi ku nkola y’ekibumba: Okunoonyereza kuzudde nti Melanotan-1 ayinza okuba n’ekikolwa eky’obukuumi ku nkola y’ekibumba y’abalwadde ba EPP. Mu kunoonyereza okwakolebwa nga batunuulidde emabega, okukebera enkola y’ekibumba 2933, okukeberebwa kw’obungi bwa protoporphyrin 1186, n’okusiiga eddagala lya Melanotan-1 1659 ku balwadde 70 aba EPP byassibwamu. Ebivuddemu biraga nti ennaku okuva lwe kyasembayo okuteekebwamu Melanotan-1 bwe zeeyongera, ekirungo kya protoporphyrin (PPIX) kyeyongera nnyo (p < 0.0001); ate mu nnaku 365 eziyise, nga ddoozi ya Melanotan-1 yeeyongera, alanine aminotransferase (ALAT) ne bilirubin byakendeera nnyo (p = 0.012, p = 0.0299). Kino kiraga nti Melanotan-1 erina ekikolwa eky’obukuumi ekisinziira ku ddoozi ku nkola y’ekibumba y’abalwadde ba EPP [5]. .
Enkolagana ya PPIX n’ebipimo by’ekibumba. Ekifaananyi (A): Histograms (green) ziraga ensaasaanya y’ebikwata ku laboratory. Okugeraageranya kwa babiri ku bikwata ku biwandiiko byonna ebya laboratory kulagibwa. Ekifaananyi (B): Ebikwata ku bibalo bya buli kigezo, omuli wakati, SD, wakati, ekitono, n’ekisinga obunene, biragiddwa.
Ensibuko:PubMed [5] .
Kkampuni ya Australia eya EpiTan ekoze okunoonyereza ku nkola empya ey’eddagala lya Melanotan (I):
Melanotan (I) ye analog ya α-melanocyte-stimulating hormone, ekozesebwa okuziyiza omusana okwonooneka. Kiyamba okukola ekirungo kya melanin, kiddugala olususu, era bwe kityo kikuuma olususu okuva ku butangaavu bwa ultraviolet.
Waliwo okunoonyereza kusatu okukakasizza obukuumi bwa Melanotan-1. Mu kunoonyereza okwasooka, abantu 4 baaweebwa mu ngeri ey’ekifuulannenge okufuna Melanotan-1 (0.08mg/kg empiso wansi w’olususu buli lunaku), ate abalala 4 ne bafuna empiso ya isotonic sodium chloride (9%) solution okumala ennaku 10, ne baddirira okubunyisa ekitangaala kya UV-B ku mirundi 3 ku ddoozi ya erythema esinga obutono (MED) ku bulago.
Ebivuddemu biraga nti abantu 3 ku 4 abaafunye Melanotan-1 baatuuka ku kulongoosa, era omuwendo gw’obutoffaali obwayokeddwa omusana mu kitundu ky’ensingo ekyaweebwa obusannyalazo bw’abantu bano gwakendeera ebitundu 47% (Dorr RT).
Mu kunoonyereza okw’okubiri, ddoozi ya MT-1 yayongezebwa okutuuka ku 0.16mg/kg buli lunaku okumala ennaku 10.
Mu kiseera (n = 7) oba oluvannyuma (n = 5) ekiseera ky’okuweebwa MT-1, ekitundu ky’enkwaso kyakwatibwa emisinde gya UV-B (0.25 - 0.75 MED). Ebivuddemu biraga nti ddoozi eya waggulu eya MT-1 yazikiiza ebitundu by’olususu ebisingawo (Dorr RT).Mu kunoonyereza okw’okusatu, abantu 8 baaweebwa mu ngeri ey’ekifuulannenge okufuna omusana ogw’ekitundu ky’omugongo okumala ennaku 3 - 5 oba okuweebwa omusana nga kwogasse 0.16mg/kg ya MT-1, ennaku 5 mu wiiki okumala wiiki 4. Ebivuddemu biraga nti okulongoosa omugongo mu kibinja kya MT-1 kwayongezebwa nnyo, era ekikolwa kino eky’okusiiga kyamala waakiri wiiki 3 okusinga eky’ekibinja ekifuga ekyafuna omusana gwokka, ate ekibinja ekifuga kyali kyetaaga obudde obusingako ebitundu 50% obw’okusiiga omusana okutuuka ku ddaala lye limu ery’okusiiga [6]..
Okukozesa Melanotan-1 mu kunoonyereza ku bulwadde bwa melanoma:
Melanoma kizimba kya lususu ekizibu ennyo, era enkola z’obujjanjabi ezikozesebwa mu kiseera kino mulimu okulongoosa, okukozesa amasannyalaze, eddagala eriweweeza ku bulwadde, n’okujjanjaba abaserikale b’omubiri. Nga MCR agonist, Melanotan-1 eyinza okukola omulimu oguyinza okujjanjaba nga elungamya okukula, okwawukana, n’okufa kw’obutoffaali bwa melanoma. Okunoonyereza okumu kulaga nti Melanotan-1 esobola okuziyiza okukula n’okulumba obutoffaali bwa melanoma n’okuleeta apoptosis y’obutoffaali bwa melanoma [7]..
Endwadde ki eza Melanotan-1 eziyinza okukozesebwa okujjanjaba?
Obulwadde bwa protoporphyria obukola emisuwa (EPP):
Erythropoietic protoporphyria ye porphyria ey’obuzaale eva ku mirimu gya ferrochelatase emitono, ekivaako okukuŋŋaanyizibwa kwa protoporphyrin mu butoffaali obumyufu, plasma, ekibumba, n’olususu. Abalwadde batera okuwulira omusana, era bwe banaabeera mu musana, bajja kufuna obubonero ng’okulumwa olususu, okusiiwa, erythema, n’okuzimba ebizimba. Melanotan-1 akendeeza ku bubonero bw’abalwadde ba EPP ng’asitula okukola melanin mu lususu n’okwongera ku bukuumi bw’olususu okuva ku masasi ga ultraviolet. Okunoonyereza kulaga nti Melanotan-1 esobola okukendeeza ennyo ku mirundi n’obuzibu bw’obutwa bw’ekitangaala mu balwadde ba EPP n’okulongoosa omutindo gw’obulamu bwabwe [8]..
Obulwadde bwa porphyria obuzaalibwa mu mubiri (CIPA):
Congenital erythropoietic porphyria bulwadde bwa buzaale obutatera kulabika mu autosomal recessive genetic, okusinga buva ku nkyukakyuka mu gene ya hydroxymethylbilane synthase (HMBS), ekivaako enkyukakyuka ya porphyrin etali ya bulijjo. Abalwadde bakwatibwa nnyo ekitangaala, era olususu n’amaaso gaabwe byangu okwonooneka. Melanotan-1 era esobola okuwa obukuumi obumu ku masasi aga ultraviolet eri abalwadde ba CIPA nga eyongera okukola melanin y’olususu n’okukendeeza ku bubonero bwabwe [9]. .
Obulwadde bw’enjuba obuyitibwa urticaria:
Ku balwadde abalina obulwadde bwa urticaria obw’enjuba, Melanotan-1 era esobola okutumbula obukuumi bw’olususu okuva ku masasi aga ultraviolet n’okukendeeza ku mirundi n’obuzibu bw’obubonero bwa urticaria [10]..
Okubumbulukuka kw’ekitangaala eky’enkula ez’enjawulo (PMLE):
Okunoonyereza kulaga nti Melanotan-1 era erina ekikolwa ekimu eky’obujjanjabi ku balwadde ba PMLE, ekiyinza okukendeeza ku kubeerawo kw’ebizimba n’okutumbula omutindo gw’obulamu bw’abalwadde [10]..
Obulwadde bwa Vitiligo:
Melanotan-1 eyinza okukola omulimu ogutali gumu mu kutumbula repigmentation y’abalwadde ba vitiligo nga etumbula okukula n’okwawukana kwa melanocytes. Wadde nga waliwo okunoonyereza okutono ennyo ku kukozesebwa kwayo mu kujjanjaba vitiligo mu kiseera kino, ebivuddemu ebisookerwako biraga obusobozi obumu [10]..
Embalabe:
Enkola y’obujjanjabi eya Melanotan-1 ku mbalabe eyinza okuba nga yeekuusa ku kulungamya kwayo abaserikale b’omubiri n’okukendeeza ku kuddamu kw’okuzimba. Okunoonyereza okumu kuzudde nti Melanotan-1 asobola okumalawo obubonero bw’okuzimba embalabe n’okutumbula okuwona kw’ebiwundu by’olususu [10]..
Obulwadde bwa Hailey-Hailey:
Melanotan-1 era eraga ebikolwa ebimu eby’obujjanjabi mu kujjanjaba obulwadde bwa Hailey-Hailey. Obulwadde buno obw’olususu obutatera kulabika bulabika ng’enfunda n’enfunda zivaamu ebizimba n’okukulugguka ku lususu. Melanotan-1 ayinza okulongoosa obubonero bw’abalwadde nga atereeza enkola y’obutoffaali bw’olususu [10]..
Mu kumaliriza, nga analog synthetic of α-melanocyte-stimulating hormone (α-MSH), Melanotan-1 (melanotan I) ya makulu nnyo mu kisaawe ky’obulamu bw’olususu. Kiyinza okwongera ku melanin mu lususu, ne kiyamba olususu okuziyiza obulungi okwonooneka kw’emisinde gya ultraviolet, bwe kityo ne kiziyiza okwokya omusana, ne kikendeeza ku kukaddiwa kw’olususu, n’okukendeeza ku bulabe bwa kookolo w’olususu. Nga ekola ku melanocortin receptor, Melanotan-1 etumbula okukola n'okusaasaana kwa melanin, okukola 'sunscreen' ey'obutonde okukuuma obutoffaali bw'olususu okuva ku kwonooneka kwa DNA okuleetebwa emisinde gya ultraviolet n'okwonooneka kwa free radicals.
Mu kujjanjaba endwadde z’olususu, Melanotan-1 era eraga omugaso oguyinza okukozesebwa. Ku buzibu bwa langi nga vitiligo, esobola okusitula emirimu gya melanocytes n’okutumbula okukola kwa melanin, okuyamba okuzzaawo langi eya bulijjo ey’olususu. Okugatta ku ekyo, era erina obusobozi obumu mu kujjanjaba endwadde ezirina langi etali ya bwenkanya nga melasma. Nga etereeza ensaasaanya n’enkyukakyuka ya melanin, esobola okulongoosa langi y’olususu n’okubeera emu.
Ng’ekirungo kya polypeptide, Melanotan-1 egenda yeeyongera okufaayo n’okunoonyereza mu by’ensusu n’okwewunda, ekiwa abantu eky’okukola ekipya eky’okukola ku bizibu ebikwata ku langi y’olususu. Kinajjukirwa nti okukozesa Melanotan-1 mu by’obujjanjabi kikyali kyetaagisa okwekenneenya ennyo. Mu kiseera kino, okunoonyereza okusinga kulina obunene bwa sampuli obutono n’ebikwata ku byokwerinda eby’ekiseera ekiwanvu ebitono. Wabula olw’okukulaakulanya enkola empya ezifuluma mu ngeri ey’olubeerera n’enkola z’okutuusa eddagala mu kitundu, essuubi lyayo ery’okuvvuunula mu bujjanjabi lisuubiza.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Elizabeth A. Langan musawo w’ensusu omututumufu mu Bungereza era omukugu mu by’obujjanjabi. Alina ebifo by’ebyensoma mu matendekero agawerako, omuli obwa Pulofeesa mu Yunivasite y’e Lubeck ne Yunivasite y’e Manchester, wamu n’emirimu mu yunivasite ya Heidelberg ne yunivasite ya Queen Mary e London. Langan akolera mu matendekero g’ebyobujjanjabi ag’ettutumu nga Schleswig-Holstein University Hospital ne Salford Royal NHS Foundation Trust. Afulumizza empapula nnyingi mu bitabo by’abakugu nga Dermatological Science. Ebitundu by’okunoonyereza bye bikwata ku by’ensusu, eby’obujjanjabi obw’enjawulo n’eby’omunda, okulongoosa, obulwadde bwa kkansa, n’obusawo bw’okunoonyereza n’okugezesa. Omulimu gwe gumanyiddwa nnyo era gukoze kinene mu by’obusawo bino. Elizabeth A. Langan awandiikiddwa mu kiwandiiko ekijuliziddwa [1].
