Abaloparatide eddagala eriweweeza ku bulwadde bwa 3mg

▎ ya Abaloparatide Enzimba

▎ bulwadde bwa Abaloparatide Okunoonyereza ku

Kiki ekikoleddwa mu kunoonyereza ku ddagala lya abaloparatide?

Obulwadde bw’amagumba bulwadde bwa magumba obutera okuvaamu ensonga nnyingi obumanyiddwa ng’amagumba amatono n’okwonooneka kw’ebitundu by’amagumba mu ngeri entonotono. Kino kivaako amagumba okweyongera okumenyamenya n’okumenya amangu, ng’okumenya ekisambi n’omugongo bye bitera okuvaamu. Kikosa nnyo omutindo gw’obulamu bw’abalwadde era kyongera ku bulemu n’okufa. Olw’okukaddiwa amangu mu nsi yonna, omuwendo gw’abalwadde b’amagumba gweyongera okweyongera. Kiteeberezebwa nti abakyala 42%-56% n’abasajja abasukka mu myaka 50 27%-29% bajja kufuna okumenya amagumba, ekigifuula ensonga ey’amangu ey’ebyobulamu by’abantu. Enzijanjaba z’amagumba ez’ekinnansi, nga bisphosphonates ne selective estrogen receptor modulators (SERMs), okusinga zikuuma density y’amagumba nga ziziyiza osteoclast-mediated bone resorption. Wabula obulungi bwazo bukoma ku balwadde abalina amagumba agakendedde ennyo n’obulabe obw’amaanyi obw’okumenya. Wadde ng’akatundu ka parathyroid hormone (PTH) 1-34 (teriparatide) ye yali ekirungo ekisooka eky’okuziyiza omusaayi ekyakkirizibwa ekitongole kya Amerika ekivunaanyizibwa ku by’emmere n’eddagala (FDA), ekyayongera obulungi ku density y’amagumba n’okukendeeza ku bulabe bw’okumenya, okukikozesa okumala ebbanga eddene kulina obuzibu omuli okwongera okunyiga amagumba, hypercalcemia, n’obulabe obuyinza obw’okwongera ku osteosarcoma.

Mu mbeera eno, okukola eddagala eppya erigatta ebikolwa eby’amaanyi eby’okuziyiza (anabolic effects) ate nga weewala ebizibu bino kyetaagisa nnyo. Nga parathyroid hormone-related peptide (PTHrP) analog, abaloparatide ekuuma emirimu gya anabolic egy’amaanyi ate nga ekendeeza ku buzibu ku kuddamu okunyiga amagumba n’okukendeeza ku nkyukakyuka za serum calcium, ekigifuula ey’omugaso mu kuzimba amagumba.

Enkola ki ez’okukola ku ddagala lya abaloparatide?

Enkolagana ne Parathyroid Hormone Receptor 1 (PTH1R) .

Okukola mu ngeri y’okulondamu eddagala: Abaloparatide ye agonist erongooseddwa ey’ekirungo kya parathyroid hormone receptor 1 (PTH1R). PTH1R yeeyolekera nnyo ku ngulu w’obutoffaali mu bitundu by’omubiri ng’amagumba n’ensigo, ng’ekola kinene mu kulungamya enkyukakyuka y’amagumba. Abaloparatide yeekwata mu ngeri ey’enjawulo ku PTH1R, n’etandika omuddirirwa gw’amakubo g’obubonero mu butoffaali okulungamya enkyukakyuka y’amagumba. Nga yesibye, ekola adenylate cyclase, eyongera okukola intracellular cyclic AMP (cAMP) okukyusa enkola y’obutoffaali n’enkyukakyuka y’emmere ^[1,2]..

Enjawulo ku ligandi endala: Obusimu obuyitibwa parathyroid hormone (PTH) ne parathyroid hormone-related protein (PTHrP) nabyo bisiba ku PTH1R. Newankubadde nga PTH, PTHrP, ne Abaloparatide zonna ziraga obubonero nga ziyita mu PTH1R, amakubo gazo ag’obubonero wansi gaawukana. PTH ne PTHrP ziraga enkolagana ezifaanagana ku mbeera ya R ^ G (GTPγS-sensitive) eya PTH1R. Teriparatid (TPTD, kwe kugamba, 1–34 PTH) erina enkolagana esingako emirundi ena eri embeera ya R ^ 0 (GTPγS-insensitive) okusinga PTHrP, ekivaamu obubonero bwa cAMP obuwanvu obuleetebwa TPTD. Okwawukana ku ekyo, abaloparatide, eggibwa mu PTHrP(1-34), ya yinginiya okusobola okutumbula okutebenkera era evvuunuka ensonga ng’okufiirwa eddirisa ly’anaabolic ne hypercalcemia ezikwatagana n’okukozesa TPTD. Olw’okuba omutindo gw’okukutuka kw’ekizibu kya PTHrP-PTH1R gwa mangu okusinga ogw’ekizibu kya PTH-PTH1R, ebikolwa by’amagumba ebya PTHrP biwerekerwako okunyiga okutono n’okukendeera kwa kalisiyamu okusinga TPTD. Abaloparatide esikira enkizo eno ey’enjawulo ^[1,2,3]..

Okulungamya Enkyukakyuka y’Emagumba

Okutumbula Osteogenesis: Abaloparatide asitula emirimu gy’amagumba, okwongera okusengejja n’okuteeka amagumba matrix okutumbula okutondebwa kw’amagumba. Osteoblasts zikola era ne zifulumya ebitundu by’amagumba nga collagen ne osteocalcin, ebigenda bifuuka mineral mpolampola ne bikola ebitundu by’amagumba ebipya. Okunoonyereza kulaga nti mu kujjanjaba obulwadde bw’amagumba obuva mu nsonga, abaloparatide eyongera nnyo ku bungi bw’amagumba (BMD) mu bifo omuli ekisambi kyonna, ensingo y’ekisambi, n’omugongo gw’omugongo. Nga esitula okwolesebwa kw’obuzaale obukwatagana n’amagumba, etereeza okusengejja obutoffaali obukulu nga osteocalcin ne kolagini ow’ekika kya I. Kino kitumbula okugonza kw’amagumba n’okunyweza ebitundu by’omubiri, okutumbula amaanyi g’amagumba n’omutindo ate nga kikendeeza ku bulabe bw’okumenya ^[1,2,3]..

Okuziyiza okuddamu okuyungibwa kw’amagumba: Wadde Abaloparatide okusinga ekola nga anabolic agent, era eraga ebimu ku bikolwa ebiziyiza okuddamu okukwata amagumba. Kikyusa enjawulo n’emirimu gy’ebiwuka ebizimba amagumba —obutoffaali obuvunaanyizibwa ku kuddamu okusikiriza amagumba obusaanuusa eby’obuggagga bw’amagumba n’ebintu ebiramu nga bufulumya ebintu ebirimu asidi n’enziyiza ezikola proteolytic. Abaloparatide eyinza okukendeeza ku miwendo gy’amagumba agaddamu okunyiga ng’ekendeeza ku njawulo y’obutoffaali obusookerwako obw’amagumba mu bitundu by’amagumba ebikuze oba okukendeeza ku bulamu bw’amagumba amakulu. Mu kiseera kye kimu, ekyusakyusa obubonero wakati w’amagumba n’amagumba, n’ekuuma emyenkanonkano ey’amaanyi wakati w’okutondebwa kw’amagumba n’okuddamu okusikiriza. Okugeza, kikendeeza ku kukola kwa osteoclast n’okuddamu okusikiriza nga kikendeeza ku osteoblast-secreted receptor activator of nuclear factor κB ligand (RANKL). Okwawukana ku teriparatide, abaloparatide teyongera nnyo kukola RANKL, bwe kityo n’eziyiza okufiirwa eddirisa lya anabolic eribaawo nga resorption esukkulumye ku kutondebwa mu mitendera egy’oluvannyuma ^[1,2,3]..

Ekifaananyi 1 Omuze gw’obusimu bwa parathyroid (PTH)/teriparatide ne peptide eyeekuusa ku PTH (PTHrP/abaloparatide activation of parathyroid hormone type 1 receptor (PTH1R)) ^[4]..

Ebikosa ku nkyukakyuka y’amagumba (mu Osteoarthritis-Related Studies)

Promotes Cartilage Matrix Synthesis: Okunoonyereza ku bulwadde bw’amagumba (OA) kulaga nti abaloparatide ekola kinene mu kukuuma eggumba. Articular chondrocytes ziraga PTH1R, era Abaloparatide ekola receptor eno, n’esitula chondrocytes okukola ebitundu by’ekisenge ky’amagumba. Okugeza, okunoonyereza kulaga nti Abaloparatide ayongera ku lubricin (Prg4) expression, protein enkulu ey’ebweru w’obutoffaali mu cartilage enkulu ennyo mu kukuuma okusiiga kw’ennyondo n’okukendeeza ku kusikagana. Era kitumbula okukola kolagini ey’ekika kya II, ekitundu ekikulu mu matrix y’amagumba, ekiyamba okukuuma obulungi ensengekera y’amagumba n’enkola y’amagumba. Nga eyongera ku kusengejja ebitundu bino eby’amagumba, Abaloparatide eyamba mu kuddaabiriza n’okukuuma ebitundu by’amagumba ebyonooneddwa, okukendeeza ku kukula kw’obulwadde bw’amagumba ^[5]..

Okuziyiza okukula kw’obutoffaali bw’omubiri (chondrocyte hypertrophy) n’okuvunda: Abaloparatide esobola okunyigiriza enkola y’enjawulo y’obutoffaali obuyitibwa chondrocytes. Mu kiseera ky’okukula kw’obulwadde bw’amagumba, chondrocytes ziyita mu njawulo ya hypertrophic, emanyiddwa olw’okweyongera kw’obunene bw’obutoffaali n’okulinnya kw’okwolesebwa kw’obubonero obw’enjawulo obw’okukula kw’amagumba nga ekika kya X kolagini (Col10). Enkola eno ereeta okuvunda kw’ekisenge ky’amagumba n’okuvunda kw’amagumba. Okunoonyereza kulaga nti obujjanjabi bwa Abaloparatide bukendeeza ku upregulation ya Col10 expression mu cartilage tissue ate nga bukendeeza ku muwendo gw’obutoffaali obunene obulinga hypertrophic. Kino kiraga nti kiyinza okukendeeza ku njawulo ya chondrocyte hypertrophic, okukuuma chondrocyte phenotype eya bulijjo, bwe kityo ne kikuuma eggumba n’okulwawo okukula kw’obulwadde bw’amagumba ^[5]..

Ebikozesebwa bya Abaloparatide bye biruwa?

Obujjanjabi bw’obulwadde bw’amagumba

Obulwadde bw’amagumba oluvannyuma lw’okuggwaamu amaanyi: Abaloparatide, eddagala eriweweeza ku busimu obuyitibwa parathyroid hormone receptor 1 (PTHR1), eragiddwa okujjanjaba obulwadde bw’amagumba naddala mu bakyala abava mu nsonga abali mu bulabe bw’okumenya oba abataddamu bujjanjabi bulala. Kyongera nnyo ku bungi bw’amagumba n’okukendeeza ku buzibu n’obulabe bw’okumenya omugongo omupya n’okutali kwa mugongo mu bakyala abava mu nsonga.

Obulwadde bw’amagumba obw’ekisajja: Mu kunoonyereza kwa Chandler H ku bulwadde bw’amagumba obw’ekisajja ng’akozesa envunza ezaalongoosebwa orchidectomized (ORX rats, a male osteoporosis model), obujjanjabi bwa Abaloparatide bwavaamu okweyongera okunene mu BMD eyapimibwa mu dual-energy X-ray absorptiometry (DXA) ne peripheral quantitative computed tomography (pQCT) mu bifo omuli omubiri gwonna, omugongo gw’omugongo, ekisambi, n’ekisambi. Yalongoosa nnyo okutondebwa kw’amagumba, obunene bw’amagumba, n’okuzimba obutonotono awatali kwongera ku muwendo gwa osteoclast. Kino kiraga nti Abaloparatide erina emigaso egisobola okujjanjaba obulwadde bw’amagumba bw’abasajja ^[6]..

Obujjanjabi bw’endwadde z’amagumba (PTOA) oluvannyuma lw’okuyingiza PTOA mu kugulu nga tuyita mu kulongoosebwa mu kulongoosa mu mbeba ensajja eza wiiki 16 eza C57BL/6, empiso za 40 μg/kg Abaloparatide (oba omunnyo ng’ezifuga) zaaweebwa okutandika ne wiiki 2 oluvannyuma lw’okulongoosebwa okumala Wiiki 6. Okwekenenya ebitundu by’omubiri kwakolebwa ku wiiki 8. Ebivuddemu biraga nti bw’ogeraageranya n’ekibinja ekyajjanjabwa omunnyo, ekibinja ekyajjanjabwa Abaloparatide kyalaga okukendeera kw’okufiirwa kw’amagumba g’ennyindo okuva ku DMM n’okukuuma ebitundu by’amagumba ag’okungulu mu tibial. Okwekenenya obusimu obuziyiza endwadde kwalaga nti obujjanjabi bwa Abaloparatide bwakendeeza ku upregulation ya type X collagen (Col10) mu cartilage, okwongera ku lubricin (Prg4) expression mu bitundu by’amagumba ebitali bya calcified, era ne bukendeeza ku muwendo gw’obutoffaali obunene hypertrophic. ekiraga nti Abaloparatide ekendeeza ku njawulo ya hypertrophic era ekola ekikolwa eky’okukuuma ennyindo mu PTOA y’ebibe, nga egaba enkola empya ey’obujjanjabi ku PTOA ^[5]..

Okuzzaawo amagumba g’omu nnyindo: Okuddamu okunyiga amagumba g’amagumba oluvannyuma lw’okuggyibwamu kiremesa nnyo okutambula kw’amannyo okuddako (OTM) oba okuteekebwa mu mannyo. Tan B yakola ebimera ebivunda, ebikola emirimu ebiri ebikola ebiramu ebiyitibwa calcium phosphate nanoblossoms (NFs) nga bitikkiddwa Abaloparatide (ABL), ebiyitibwa ABL@NFs. Ekintu kino kyoleka ensengekera ya porous layered, high drug encapsulation efficiency, ne biocompatibility ennungi. ABL yasooka kufulumizibwa okuwandiika obutoffaali obusibuka, n’eddirirwa okufulumya okuwangaala kwa Ca⊃2;9 ne PO4⊃3;− okusobola okukola in situ interfacial mineralization. Kino kyazzaawo bulungi eggumba ly’amagumba erikola mu nkula n’emirimu awatali kufiiriza OTM ^[7]..

Refractory Hypoparathyroidism (HPT): Chamseddin R yategeeza nti omukyala ow’emyaka 39 alina obulwadde bwa iatrogenic HPT eyalemererwa okutuuka ku muwendo gwa calcium ogwa bulijjo mu musaayi wadde nga yafukibwako vitamiini D ya dose ennene, eddagala lya calcium, n’empiso za PTH (rPTH) ezigatta. Oluvannyuma lw’okuweebwa eddagala lya abaloparatide wansi w’olususu ng’ayita mu kitundu kya Simplicity ng’alondoola nnyo n’okuweebwa ddoozi ey’obuntu, calcium ye mu musaayi yasigala nga tekyukakyuka ku 9 mg/dL oluvannyuma lw’emyezi 2. Ku myezi 4, yakuuma calcium mu musaayi eya bulijjo nga talina biseera bya hypocalcemia ate nga mpolampola akendeeza ku calcium mu kamwa ne vitamin D supplementation ^[3]..

Okutumbula okuyungibwa kw’omugongo: Mu kulongoosa omumwa gwa nnabaana n’ekifuba, abaloparatide yakozesebwa okutumbula okuyungibwa kw’omugongo mu balwadde abalina ebyafaayo by’obutabeera mu ntebenkevu mu nnabaana n’okulongoosa omumwa gwa nnabaana emirundi mingi ne balemererwa. Parikh S ne banne. yategeeza omulwadde omukyala ow’emyaka 66 eyatandika obujjanjabi bwa Abaloparatide obwa 80 mcg buli lunaku nga wayise wiiki bbiri ng’amaze okulongoosebwa olw’omusomo ogwategekebwa okumala wiiki 12. CT scans z’omumwa gwa nnabaana ku myezi 3 ne 6 zalaga okuyungibwa kw’omumwa gwa nnabaana n’ekifuba nga kuwonye bulungi nga tewali kabonero ka butakwatagana ^[8]..

Mu bufunzi

Abaloparatide okukozesebwa mu bujjanjabi kwesigamye ku bujjanjabi bw’obulwadde bw’amagumba. Kilagibwa eri abakyala abava mu nsonga abalina obulwadde bw’amagumba abali mu bulabe obw’amaanyi obw’okumenya oba nga tebaddamu bujjanjabi bulala, okwongera ennyo ku bungi bw’amagumba (BMD) n’okukendeeza ku bulabe bw’okumenya omugongo n’obutali mu mugongo. Ku bulwadde bw’amagumba bw’abasajja, okunoonyereza ku bisolo kulaga okweyongera kwa BMD mu bifo ebingi n’okulongoosa mu microarchitecture y’amagumba, ekiraga nti omugaso oguyinza okujjanjaba. Mu bulwadde bw’amagumba obuva ku buvune, bukendeeza ku kufiirwa kw’amagumba n’okuziyiza okukula kw’obutoffaali obuyitibwa chondrocyte hypertrophy okukuuma eggumba. Mu kuzzaawo amagumba g’amagumba, ebintu bya ABL@NFs ebitikkiddwa eddagala lino bitumbula okuddamu okukola amagumba, nga biwa eky’okugonjoola okuddaabiriza amagumba oluvannyuma lw’okulongoosa amannyo. Okunoonyereza era kuwagira enkozesa yaayo mu refractory hypoparathyroidism n’okutumbula okuyungibwa kw’omugongo.

Ebikwata ku Muwandiisi

Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.

Omuwandiisi wa Scientific Journal

Bin T munoonyereza mu kitongole kya Chemistry, Peking University, ng’akuguse mu nanomaterials n’okuzikozesa mu biomedical engineering. Omulimu gwe gussa essira ku kukola n’okusengejja nanostructures ezikola okusobola okutuusa eddagala erigendereddwamu n’okuzza obuggya ebitundu by’omubiri. Tan abadde omu ku bawandiisi ebitabo bingi mu bitabo bya ssaayansi ebikulembedde, n’ayambako mu nkulaakulana mu nanomedicine n’obujjanjabi obuzza obuggya. Bin T ewandiikiddwa mu kiwandiiko ekijuliziddwa mu kiwandiiko ekijuliziddwa [7].

▎ Ebiwandiiko Ebikwatagana

[1] Shirley M. Abaloparatide: Okusooka okukkirizibwa mu nsi yonna. Eddagala 2017; 77 (12): 1363-1368.DOI: 10.1007/s40265-017-0780-7.

[2] Sleeman A, Clements JN, ne bannaabwe abalala. Abaloparatide: Enkola empya ey’eddagala eriwonya obulwadde bw’amagumba. Ekitabo ky’Amerika eky’Eddagala ly’Enkola y’Ebyobulamu 2019; 76: 130-135.Eby’obutonde bw’ensi mu bitundu by’eggwanga eby’enjawulo.

[3] Chamseddin R, Mathew A, Alzohaili O. Abstract #1407986: Okugaba Abaloparatide Okuyita mu Simplicity Patch: Enkola ey'obujjanjabi ku Refractory Hypoparathyroidism Oluvannyuma lw'okuggyibwako thyroid. Enkola y’Endocrine 2023; 29: S57-S58.DOI: 10.1016/j.eprac.2023.03.131.

[4] Thompson JC, Wanderman N, Anderson P. A., Freedman B. A., ne bannaabwe abalala. Abaloparatide n’omugongo: Okuddamu okwetegereza ennyiriri. Ebikolwa by’obujjanjabi mu kukaddiwa 2020; 15: 1023-1033. DOI:10.2147/CIA.S227611.Ekitongole ky’ebyobulamu.

[5] Landgrave S, Ishii T, Maynard R, n’abalala. 302 Abaloparatide nga obujjanjabi obupya ku bulwadde bw’amagumba oluvannyuma lw’okukosebwa. Journal of Sayansi w’obujjanjabi n’okuvvuunula 2022; 6: 53. DOI:10.1017/cts.2022.166.

[6] Chandler H, Lanske B, Varela A, n’abalala. Abaloparatide, novel osteoanabolic PTHrP analog, eyongera ku cortical ne trabecular bone mass n’enzimba mu nvunza ezisaliddwa orchiectomized nga eyongera ku kutondebwa kw’amagumba awatali kwongera ku bone resorption. Eggumba 2019; 120: 148-155.DOI: 10.1016/j.eggumba.2018.10.012.

[7] Tan B, Wu Y, Wang R, n’abalala. Ebimuli bya Nano ebivunda mu biramu nga biriko Abaloparatide Spatiotemporal Management y’okuzza obuggya amagumba g’omu bitundu by’omubiri agakola. Ebbaluwa za Nano 2024. https://api.semanticscholar.org/CorpusID:267655299. Enkola y’okukuuma obutonde bw’ensi.

[8] Parikh S, Lubitz SE, Sharma A. MON-365 Novel Enkozesa ya Abaloparatide okwongera ku Spinal Fusion mu mulwadde alongoosebwa Cervicothoracic Revision. Journal of Ekibiina ky’Endocrine 2020; 4 (Eby’okugattako_1): 365.DOI: 10.1210/jendso/bvaa046.108.

EBINTU BYONNNA N’AMAWULIRE GW’EBINTU EBIweereddwa KU MUTINDO GUNO BIKOZESEBWA KU KUSASANYA AMAWULIRE N’EBIKOLWA BY’OKUSOMESA BYOKKA.  

Ebintu ebiweereddwa ku mukutu guno bigendereddwamu kunoonyereza mu kisenge (in vitro research) byokka. Okunoonyereza mu kisenge (in vitro research) (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.