Oligonucleotide kev kho mob, suav nrog antisense oligonucleotides (ASOs) thiab siRNAs, tau dhau los ua ib qho kev kho mob tseem ceeb rau cov kab mob hauv nruab nrab ntawm lub paj hlwb (CNS). Vim hais tias cov loj, tsis zoo nqi molecules no tsis tau zoo hla cov ntshav -b hlwb teeb meem, intrathecal tswj muab lawv ncaj qha mus rau hauv lub cerebrospinal kua (CSF), ua kom muaj kev faib thoob plaws hauv lub CNS thaum txo cov kab mob kis thiab txhim kho kev kho mob.
Intrathecal tus me nyuam tau raug kuaj xyuas los ntawm kev kho mob xws li nusinersen rau tus txha caj qaum atrophy thiab tau siv ntau ntxiv hauv kev kho mob rau cov kab mob neurodegenerative. Tom qab kev tswj hwm, oligonucleotides faib sai sai hauv CNS, nthuav tawm cov ntaub so ntswg ntev, thiab feem ntau metabolized los ntawm nucleases ua ntej tshem tawm lub raum. Yog li ntawd, cov kev tshawb fawb preclinical yuav tsum ntsuas ob qho tib si pharmacokinetics thiab CNS- cov kev txwv tshwj xeeb, suav nrog kev faib tshuaj, metabolite profiles, CSF raug, thiab pharmacodynamic biomarkers hauv cov ntaub so ntswg.
Raws li CNS kev txhim kho tshuaj txuas ntxiv mus, txhim khu kev qha intrathecal dosing thiab CSF sampling cov txheej txheem yog qhov tseem ceeb rau kev tsim cov ntaub ntawv zoo - PK / PD. Cov txheej txheem preclinical muaj zog uas ua ke nrog kev tswj hwm intrathecal nrog kev tshawb fawb txog CNS cov kws kho mob tuaj yeem ua kom txoj kev loj hlob thiab kev txhais lus ntawm oligonucleotide kho mob rau cov kab mob neurological.
