Cov txiaj ntsig ntawm Risdiplam Powder Rau Tib Neeg Kev Noj Qab Haus Huv yog dab tsi?

Risdiplam Powder, ib qho tshuaj tshiab ntawm qhov ncauj me me molecule, tau dhau los ua qhov kev xaiv kho mob tseem ceeb hauv thaj tsam ntawm tus txha caj qaum atrophy (SMA). Tsab ntawv xov xwm no muab kev txhais lus dav dav thiab cov txheej txheem ntawm Risdiplam Powder los ntawm qhov kev xav ntawm cov yam ntxwv ntawm cov tshuaj, kev siv tshuaj kho mob, cov hom phiaj, kev pheej hmoo thiab kev tsis zoo, lwm txoj kev kho mob, thiab cov lus pom zoo hauv kev lag luam, txhawm rau muab cov ntaub ntawv tshawb fawb thiab cov ntaub ntawv pov thawj rau kev tshawb fawb thiab kev txiav txim siab kho mob- ua.

Risdiplam Powder yog cov khoom siv tshuaj nquag (API) daim ntawv ntawm risdiplam, me me molecule SMN2 gene splicing modifier. API feem ntau yog siv los tsim cov ntawv qhia qhov ncauj rau kev kho mob ntawm 5q-hom spinal muscular atrophy (SMA). Keeb kwm tsim los ntawm Roche thiab PTC Therapeutics, risdiplam tau txais kev pom zoo kev lag luam hauv ntau lub teb chaws thiab cheeb tsam suav nrog Tebchaws Europe thiab Tebchaws Meskas. Nws cov txheej txheem cuam tshuam nrog kev hloov pauv qhov sib txuas ntawm SMN2 gene precursor mRNA los txhawb kev tsim cov SMN protein ua haujlwm, yog li txhim kho txoj sia nyob ntawm lub cev muaj zog neurons.

Tus nqi kho mob tseem ceeb ntawm risdiplam cov khoom tiav yog nyob rau hauv lawv qhov ncauj kev tswj hwm, uas ua rau muaj txiaj ntsig zoo ntawm SMN protein ntau hauv cov neeg mob, yog li ua rau qeeb tus kab mob, txhim kho lub cev muaj zog, thiab txhim kho lub neej zoo hauv SMA cov neeg mob. Cov kev tshawb fawb soj ntsuam dav dav (xws li FIREFISH thiab SUNFISH) tau pom tias risdiplam txhim kho lub cev muaj zog thiab txo cov teeb meem ua pa hauv SMA cov neeg mob hnub nyoog 2 hlis thiab laus dua, ua rau muaj kev muaj sia nyob ntxiv. Tam sim no, tsis muaj pov thawj tias risdiplam cuam tshuam ncaj qha rau kev tswj qhov hnyav; Kev hloov pauv qhov hnyav yog feem ntau cuam tshuam nrog kev noj qab haus huv tag nrho thiab kev txhawb nqa kev noj haus ntawm tus neeg mob. Risdiplam ua feem ntau ntawm cov kab mob neuromuscular thiab tsis ncaj qha tswj lub cev rog lossis metabolism.

Risdiplam hmoov-raws li cov khoom lag luam tau qhia rau cov neeg mob kuaj mob nrog 5q- hom txha caj qaum atrophy, nthuav dav ntau yam nrog rau cov menyuam mos hnub nyoog 2 hlis thiab siab dua, menyuam yaus, thiab cov neeg laus. Nws cov lus qhia suav nrog SMA hom 1, 2, thiab 3, tshwj xeeb tshaj yog haum rau cov neeg mob uas tsis tuaj yeem lossis tsis haum rau kev txhaj tshuaj intrathecal. Cov neeg mob uas muaj homozygous tshem tawm lossis hloov pauv ntawm SMN1 noob thiab tsawg kawg ib daim qauv ntawm SMN2 qhia meej cov txiaj ntsig kho mob los ntawm risdiplam.

Kev sim tshuaj thiab qhov tseeb-cov ntaub ntawv hauv ntiaj teb qhia tias kev txhim kho thawj zaug hauv lub cev muaj zog tuaj yeem pom nyob rau hauv kwv yees li 4 mus rau 8 lub lis piam tom qab pib kho risdiplam. Qee tus me nyuam mos uas muaj hom 1 SMA qhia qhov kev hloov pauv tseem ceeb hauv 4 lub lis piam, thaum hom 2 thiab 3 SMA cov neeg mob feem ntau xav tau 8 lub lis piam lossis ntev dua los soj ntsuam cov teebmeem. Qhov pib ntawm kev ua tau zoo yog cuam tshuam nrog cov neeg mob hnub nyoog, SMA subtype, thiab lub hauv paus kev ua haujlwm ntawm kev pib kho. Nrog kev kho mob tas mus li thiab tsim nyog rau 6 lub hlis lossis ntau dua, cov neeg mob feem ntau pom muaj kev txhim kho tseem ceeb hauv lub cev muaj zog thiab txo cov teeb meem.

Los ntawm kev tshawb fawb thiab kev soj ntsuam kev saib xyuas, risdiplam hmoov-raws li cov khoom lag luam yog contraindicated rau cov neeg tsis haum rau risdiplam los yog ib qho ntawm nws cov excipients. Cov poj niam cev xeeb tub thiab lactating poj niam yuav tsum ua tib zoo ntsuas qhov txaus ntshai thiab cov txiaj ntsig, thiab siv cov tshuaj kom ceev faj tsuas yog thaum cov txiaj ntsig pom tseeb. Cov neeg mob uas muaj kab mob siab lossis lub raum tsis zoo yuav tsum tau hloov kho koob tshuaj ib leeg lossis saib xyuas ze. Thaum kho, kev soj ntsuam xyuas cov ntshav ib ntus, lub siab thiab lub raum kev ua haujlwm, thiab kev kuaj mob ophthalmologic raug pom zoo rau kev tshawb pom ntxov ntawm qhov tsis zoo.

Cov kev phiv tshwm sim muaj xws li kub taub hau, ua pob liab liab, raws plab, xeev siab, stomatitis, thiab mob taub hau. Qee tus neeg mob tuaj yeem ua rau lub siab enzymes siab, hematologic abnormalities (xws li leukopenia thiab thrombocytopenia), thiab retinal abnormalities. Kev tsis haum tshuaj hnyav yog tsawg. Lub sijhawm ntev - cov ntaub ntawv kev nyab xeeb tseem raug sau los ntawm kev soj ntsuam thiab kev tshawb fawb tsis tu ncua. Nws raug nquahu kom cov neeg mob tau txais kev kuaj mob tsis tu ncua thiab kev soj ntsuam kuaj mob kom sai thiab tswj xyuas cov xwm txheej tsis zoo.

Tam sim no, lwm cov kev kho mob pom zoo rau SMA suav nrog Nusinersen (intrathecal txhaj) thiab Onasemnogene Abeparvovec (gene therapy). Nusinersen yog haum rau txhua hom SMA thiab yuav tsum muaj kev tswj hwm intrathecal; Onasemnogene Abeparvovec yog ib qho -lub sij hawm AAV gene therapy qhia rau cov neeg mob hnub nyoog qis dua 2 xyoos. Kev xaiv tshuaj yuav tsum xav txog cov neeg mob hnub nyoog, SMA subtype, kev lag luam thiab kev saib xyuas kev noj qab haus huv, thiab ua raws li kev soj ntsuam ntawm pab pawg neeg sib txawv (MDT) los tsim cov phiaj xwm kho mob rau tus kheej.

Risdiplam hmoov sawv cev rau ib qho tseem ceeb ntawm cov tshuaj tshiab nyob rau hauv SMA teb, nrog rau nws qhov ncauj formulation zoo heev pab cov neeg mob yooj yim thiab ua raws li. Raws li thawj lub qhov ncauj SMN2 splicing modifier, risdiplam tau txhim kho cov txiaj ntsig ntawm kev kho mob rau cov neeg mob SMA thiab ua rau qhov sib txawv ntawm kev kho mob rau cov neeg tsis tuaj yeem zam cov tshuaj intrathecal. Kev tshawb fawb yav tom ntej yuav ua pov thawj ntxiv nws qhov profile kev nyab xeeb thiab kev ua haujlwm ntev -. Kev xaiv cov tshuaj tshawb fawb thiab kev tswj hwm tus qauv yuav muab SMA cov neeg mob nrog kev txhim kho kev ciaj sia thiab lub neej zoo.

Cov ntaub ntawv
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https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31621-4/fulltext

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