VHURUMENDE 30, NYAYA 1 • Kurume 2026. Nyaya yakazara »
Kurapa kweAtaxia: Chii Chinoshanda, Chii Chitsva, uye Chii Chinotevera
Musangano wePan American Parkinson's Disease and Movement Disorders Congress muHouston, Texas, USA, wakabatanidza musangano wevanhu vose wakatsaurirwa kukurapa kweataxia. Musangano uyu wakatanga kurongwa naMario Cornejo-Olivas (Peru) uye wakatungamirirwa naOrlando Barsottini (Brazil) naMalco Rossi (Argentina). Wakapa ruzivo nezvekurapa kuri kushandiswa pari zvino, mishonga mitsva, uye mishonga yeramangwana, kusanganisira mishonga yemajini.
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Chii chinoshanda mu ataxia? Kugadzirisa kutarisirwa nhasi
Muhurukuro inoti “Chii chinoshanda mu ataxia? Kugadzirisa hutano nhasi,” José Luiz Pedroso (Brazil) akapa ruzivo rwemamiriro aripo ekurapa ataxia, achiongorora nzira dzekurapa dzakasimbiswa uye ruzivo rwemunhu. Ataxias ichiri pakati pezvirwere zvinonyanya kurapa muuropi. Mazana emiedzo, asi kuvandudzika kushoma kunobudirira kunoonekwa muvarwere vane ataxia inoderera.
Tichifunga izvi, zvinhu zvitatu zvikuru zvinofanirwa kufungwa nezvazvo pakurapa ataxias: |
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Mumuenzaniso uyu, nhanho nhatu dzekurapa dzinokurudzirwa: kurapwa kwezviratidzo (kuvandudza kufamba, kutaura, kudedera, kuenzana; hakuchinje maitiro echirwere); kurapwa kunochinja chirwere (kunonotsa kufambira mberi; kunochengetedza network yecerebellar); uye kurapwa kwakanangana ne etiology (kunongogoneka chete muvanhu vashoma vane ataxia).
Kurapa kwakanangana nechikonzero chechirwere uye ataxias inorapika zvinosanganisira: abetalipoproteinemia (kuwedzera vhitamini E neA); ataxia ine kushomeka kwevhitamini E: kuwedzera vhitamini E; cerebrotendinous xanthomatosis (CTX): chenodeoxycholic acid (CDCA); CoQ10 kushomeka: kuwedzera vhitamini E; GLUT1 kushomeka: ketogenic diet; Refsum's disease: kudya kushoma mu phytanic acid uye macalorie akawanda; NPC: miglustat; Episodic ataxia: acetazolamide; secondary ataxias: Kushomeka kwevhitamini / autoimmune ataxia (Semuenzaniso Anti-GAD).
Zviratidzo zvisiri zvecerebellar zvinowanzoonekwa muvarwere vane degenerative ataxias. Saka, kurapwa kwezviratidzo kunogona kusanganisira: amantadine yekuneta (SCA3 nedzimwe SCA); baclofen / tizanidine / botulinum toxin yekupwanya: spastic ataxias (SCAs / SPG / ARSACS); levodopa yeparkinsonism (SCA3 / SCAs / RFC1 / MAS-C); trihexyphenidyl yedystonia (SCA3 / dzimwe SCAs); clonazepam uye melatonin yeRBD (SCA3 / MAS-C); ciclobenzaprin, carbamazepin uye gabapentin yekurwadziwa nekurwadziwa (SCA3).
Kurapwa kwemuviri kwakatsanangurwa senzira yekurapa yakakodzera, uye kune humwe humbowo hunowanzo shanda pakuvandudza zviratidzo zvevarwere vane cerebellar ataxia. Kudzidziswa kwakanangana kunodiwa kune varwere vane cerebellar ataxia, uye kunofanirwa kutarisa pakufamba, kugamuchira nhengo, kuenzana, kubatana, kudzora chimiro, kugadzikana kwemuviri, simba uye kuramba, kudzidziswa kwebasa, uye kurapwa kwekutaura. Pasinei nemhedzisiro yakanaka, hapana humbowo hwakajeka hwekuti kurapwa kunogona kuchinja nhoroondo yechisikigo yemaitiro ekuora kwetsinga.
Mamwe marapirwo akadai sekusapindirana kweuropi akakurukurwawo, akadai se transcranial magnetic resonance (TMS). Pfungwa dzakanaka dzinosanganisira: pfungwa dzakasimba dze neurophysiological, kuchengetedzeka, kusapindirana, kugona kushanda pamwe nekurapwa, zviratidzo zvekutanga zvekubatsira kwezviratidzo; uye zvakaipa zvinosanganisira humbowo husina kunaka, kusiyana, kusawirirana kweprotocol/mhedzisiro, kugara kwenguva refu kusina chokwadi uye kushanda zvakanaka kwemari. Mukupedzisa, humbowo husina kunaka hwakaratidza mhedzisiro inoshanda neTMS mu cerebellar ataxia.
Chii chitsva mukurapa ataxia
Muhurukuro inoti “Chii chitsva mukurapa kweataxia,” Sergio Rodriguez-Quiroga (Argentina) akatsanangura kuti kare, kurapwa kwemishonga yeataxias yenhaka kwave kuchingogumira panzira dzezviratidzo. Zvisinei, nhasi uno, tiri kupinda munguva yakaoma uye ine tariro, sezvo kufambira mberi kwazvino kuchiratidza shanduko ine chinangwa munharaunda yekurapa (Ariello, 2025). Mienzaniso inotevera inoratidza shanduko iyi.
Troriluzole, ichitarisa toxicity inokonzerwa neglutamate, yakaongororwa mumhando dzakasiyana dzeSCA muchidzidzo chekupedzisira (NCT03701399) chisina kusvika pachinangwa chayo chikuru; ongororo dzekutsvaga dzakaratidza kuti SCA3 inogona kubatsira, uye kuenzanisa nemapoka enhoroondo yezvisikwa zvakaenderana kwakaratidza kufambira mberi kunonoka. Zvimwe zvidzidzo zvinodiwa kuti zvitsanangure basa rayo mukurapa.
Friedreich's ataxia (FA, ATX-FXN) inopa mumwe muenzaniso wekufambira mberi kukuru kwakaitwa mumakore gumi apfuura mukutsvagisa kweataxia. Zviitiko zvikuru zvakawanikwa mukutsanangura pathophysiology yezvirwere, kuona zvinangwa zvekurapa, uye kutsanangura nhoroondo yechisikigo yechirwere ichi. Vatiquinone, yakanangana nenzira dzekushushikana kweoxidative, yakaongororwa muchidzidzo cheMOVE-FA (NCT04577352). Zvisinei, bvunzo yakakosha haina kusvika pamhedzisiro yayo yekutanga yekushanda. Kunyangwe ichikurudzira kubva pamaonero emakaniki, zvidzidzo zvakawanda zvichadikanwa kuti zvitsanangure zviri nani kubatsira kwayo mukiriniki. Zvichivakira pakufambira mberi kwesainzi uku, omaveloxolone yakabuda senzira yekutanga yekurapa chirwere cheFA, ichiratidza danho rakakosha kufambira mberi mumunda (Indelicato, 2025). Zvichibva pamhedzisiro yeMOXIe bvunzo (Lynch, 2021) uye yakatevera open-label extension uye ongororo yenguva refu (Lynch, 2024), omaveloxolone yakaratidza kuvandudzika mukushanda kwetsinga zvichienzaniswa ne placebo pamavhiki makumi mana nemasere, sezvakayerwa ne mFARS, nedata renguva refu richiratidza kuti kune purofiti inogara iripo uye kufambira mberi kwechirwere kunononoka. Ruzivo rwechokwadi ruri kuumba zvishoma nezvishoma matsananguriro atinoita mhedzisiro yaro yekiriniki uye kuibatanidza mukuita kwakajairika. Zvisinei, rwendo rwekurapa muFA haruna kuperera. Chidzidzo cheBRAVE chiri kuenderera mberi muvarwere vevana (NCT06953583) chinoratidza danho rakakosha rekuwedzera kurapwa kuvanhu vadiki uye kunzwisisa zviri nani mhedzisiro yenguva refu. Zvakakosha, kuwana uye kushandisa kunosiyana zvakanyanya munzvimbo dzakasiyana. MuLatin America, ruzivo ne omaveloxolone rwuri kutanga, sezvo mvumo yakapihwa munyika shoma. Kudzidza kubva kunzvimbo dzine ruzivo rwakakura rwekiriniki kuchave kwakakosha kuti tiwedzere kubatanidzwa kwayo mukutarisira kwakajairika.
Kurapa kweAtaxia kuri kuchinja zviri pachena. Kufambira mberi kuri kukurukurwa kunoratidza munda uri kuchinja, uko nzira dzinotungamirirwa nemaitiro uye miedzo yekupedzisira iri kutanga kuchinja maitiro ekurapa. Kunyange hazvo matambudziko akakosha achiripo, munda uyu uri kufambira mberi zviri pachena.
Chii chinotevera mukurapa ataxia
Muhurukuro inoti “Chii chinotevera mukurapa kweataxia,” Christopher Stephen (USA) akaziva kuti tava munguva yekurapa kwemajini ezvirwere zvekufamba kwemajini (Vázquez-Mojena, 2021; Sartorelli, 2025). Iyi inguva inonakidza zvikuru, kunyanya semune mamwe mamiriro etsinga, akadai sekuora kwemusana kwemusana, kwave nekubudirira kukuru. Zvisinei, kurapwa kwemajini muataxias kwave kwakaoma zvikuru. Chikonzero chekushandisa tekinoroji iyi muataxias yemajini chinosanganisira kugadzirisa chinokonzera matambudziko aya uye kubudirira kwepamberi pekiriniki, nemhando dzakasimba dzemhuka muFA neSCAs. Muataxias dzakawanda, nzira dzekunyaradza majini dzinoshandiswa, nepo muFA, izvi zvinosanganisira nzira dzekuwedzera majini.
Kurapa kwemajini kwakabatana neataxias kwakakurukurwa, kusanganisira: |
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1. Antisense oligonucleotides (ASOs), uko DNA kana RNA yakagadzirwa inosanganiswa ne mRNA kana micro RNA uye inodzivirira kugadzirwa kwemapuroteni ane chepfu, uye inoda kupiwa kakawanda; 2. Adenovirus associated vectors (AAVs), apo maAAV anoendesa majini ekurapa musero, iro rinogara riripo, richida kupiwa kamwe chete; 3. Kupindirana kweRNA (RNAi), uko magene madiki anonyaradza mamwe majini, achiadzivirira kugadzira mapuroteni anokuvadza, uye achida kupiwa kakawanda; 4. Kugadziriswa kwemajini eCRISPR, uko majini anotarisirwa anogadziriswa zvakananga, izvo zvinogara zviripo. |
Zvakanakira nezvakaipa zvemhando idzi dzekurapa kwemajini eataxias zvakaenzaniswa. Dambudziko nderekuti nzira idzi dzekurapa dzinoda kupiwa mishonga inorwisa mabhakitiriya kuti kurapwa kusvike kunzvimbo dzakakodzera dzeuropi netsinga dzepakati, kazhinji dzinosanganisira majekiseni munzvimbo dzakasiyana-siyana, kusanganisira majekiseni emukati meparenchymal (cerebral/cerebellum), majekiseni emukati meuropi, cisnational, uye lumbar intrathecal, kana musanganiswa weizvi, zvichitakura njodzi kubva mukuita uku.
Hurukuro iyi yaisanganisirawo nyaya dzakabudirira dzekurapa kweAAV muvacheche vane chirwere chisingawanzoitiki che metabolic ataxias GM2 gangliosidosis (Eichler, 2025) uye chirwere cheCanavan (Corti, 2023). Muzviitiko izvi, vacheche vakakwanisa kurarama kwenguva yakareba uye vasina simba rekufamba zvakanaka, uye vari kuita matanho akakosha mumamiriro ezvinhu aya akaipisisa. Zvisinei, pave nekubudirira kushoma pakuyedzwa muvana vakuru, izvo zvakaganhurirwawo nemigumisiro (semuenzaniso, dystonia muvechidiki GM gangliosidosis). Kuedzwa kweASO muchirwere cheAlexander (NCT04849741), nemhedzisiro inokurudzira, kwakataurwa. Miedzo yekiriniki yekurapa majini yakakurukurwawo. Kune miedzo yeASO iripo pari zvino mu spinocerebellar ataxias, kunyangwe paine kunetseka mushure mekunge bvunzo yeASO ye tominersen muchirwere cheHuntington yakonzera zviratidzo zvakanyanya, zvikaita kuti bvunzo yeSCA3 imire muna 2023. Pamusoro pezvo, miedzo yeAAV muFA yakakurukurwa, kusanganisira kukurudzira data repamusoro mukuyedzwa kweFA cardiomyopathy (NCT05445323), iyo yakaratidza kuvandudzika kwekutaura kwefrataxin yemwoyo uye left ventricular mass index.
Pakupedzisira, mukana wekushandisa mishonga yakasiyana-siyana, pamwe nemiedzo yeN ye1, uri kuramba uchiwanda (Dies, 2026). Zvisinei, tinofanira kuziva kuti tiri mumatanho ekutanga ekushandisa matekinoroji aya anogona kuchinja, ayo achiri nenjodzi huru; asi kuti izvi zvichavandudzika nekufamba kwenguva, zvichizoguma nekurapwa kana kurapwa kunoshanda zvikuru. Asi pachava nemiedzo yakawanda nematambudziko ekukunda tisati tasvika ikoko.
Musangano uyu wakapera nehurukuro inonakidza nevateereri, ichiratidza kufarira kuri kukura uye zvinotarisirwa pamusoro pekurapa kweataxia. Vatori vechikamu vakabvunza mibvunzo yakati wandei ine musoro nezvekushandiswa kuri kuitwa mishonga mitsva, kuvandudzwa kwenzira dzinoshandiswa nemajini, uye matambudziko ekushandura kufambira mberi uku kuita mabasa ekurapa. Kunyanya kutariswa kwakapihwa kune zvipingamupinyi muLatin America, zvinosanganisira mukana mushoma wekuongororwa kwemajini, kunonoka kuongororwa, misiyano yemitemo, uye kusawanikwa kwakakwana kwemishonga mitsva yakatenderwa. Hurukuro idzi dzakaratidza kukosha kwekushandira pamwe kwenyika dzese, kugovana ruzivo, uye kuvaka kugona kwenzvimbo kuti ive nechokwadi chekuti kufambira mberi mukurapa kweataxia kunogona kuitwa zvakaenzana munzvimbo dzakasiyana dzehutano.
Kukurukurirana kwakasimba kwakasimbisa kufara nekungwarira kuripo panguva ino mukutsvaga kweataxia, sezvo munda uyu uchienderera mberi nekuenda kunzira dzekurapa dzinoshanda uye dziri nyore kuwana.
References
Ariello L, Rastall D, Rosenthal L. Kurapa kweatoksia yeuropi inopinda muuropi yevakuru. Neurotherapeutics. 2025 Zvita 11:e00805
Corti M, Byrne B, Gessler D, nevamwe. Kurapa kwemajini kunokonzerwa neAdeno-associated virus-mediated gene mumurwere ane chirwere cheCanavan uchishandisa nzira mbiri dzekurapa uye immune modulation. Mol Ther Methods Clin Dev. 2023 Chikumi 19:30:303-314.
Dies K, Yu T, Chamberlin N, nevamwe. Basa reAcademic Medical Centers muKuvandudza Kurapa Kwekuyedza Kwakazvimiririra: Zvinhu Zvikuru Zvinofungwa. Neurology. 2026 Kukadzi 10;106(3):e214610
Eichler F, Cataltepe O, Daci R, nevamwe. Kurapa kwemajini maviri e-rAAVrh8 eGM2 gangliosidosis: kuyedzwa kwechikamu 1/2. Nat Med. 2025 Gunyana;31(9):2927-2935.
Indelicato E, Delatycki M, Farmer J, nevamwe. Maonero epasi rose pamusoro pekufambira mberi kwekutsvagisa nematambudziko emangwana muFriedreich ataxia. Nat Rev Neurol. 2025 Kubvumbi;21(4):204-215.
Lynch D, Chin M, Delatycki M, nevamwe. Kuchengetedzwa uye Kushanda kweOmaveloxolone muFriedreich Ataxia (Ongororo yeMOXIe). Ann Neurol. 2021 Kukadzi;89(2):212-225.
Lynch D, Goldsberry A, Rummey C, nevamwe. Kufungidzira kwakaenzanisa kuenzanisa kwekurapwa kweomaveloxolone nedata reFriedreich renhoroondo yeataxia. Ann Clin Transl Neurol. 2024 Ndira;11(1):4-16.
Sartorelli J, Ng J, Rahim A, nevamwe. Kurapa kwemajini ekusagadzikana kwekufamba - mamiriro azvino. J Neurol. 2025 Kukadzi 22;272(3):220.
Vázquez-Mojena Y, León-Arcia K, González-Zaldivar Y, et al. Gene Therapy yePolyglutamine Spinocerebellar Ataxias: Kufambira mberi, Matambudziko, uye Maonero. Mov Disord. 2021 Dec;36(12):2731-2744.
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