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New Approaches and Approved Drugs in Spinal Muscular Atrophy Tedavisinde Yeni Yaklasimlar ve Onayli Ilaclar

Saracaloglu, Ahmet ; Demiryurek, Abdullah Tuncay

Güncel pediatri, 2021-08, Vol.19 (2), p.248 [Periódico revisado por pares]

Galenos Yayinevi Tic. Ltd

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  • Título:
    New Approaches and Approved Drugs in Spinal Muscular Atrophy Tedavisinde Yeni Yaklasimlar ve Onayli Ilaclar
  • Autor: Saracaloglu, Ahmet ; Demiryurek, Abdullah Tuncay
  • Assuntos: Drug therapy ; Genetic aspects ; Pediatric research ; Spinal muscular atrophy
  • É parte de: Güncel pediatri, 2021-08, Vol.19 (2), p.248
  • Descrição: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease lead to by deletions or mutations in the survival motor neuron (SMN1) gene. SMA is the most common inherited cause of childhood mortality. SMN1 exists as a single copy in the genome of all eukaryotic organisms. Genomic duplication causes a second gene, SMN2 in humans. Approximately 95% of SMA patient has homozygous deletions in exon 7 of SMN1. Thus, SMN protein can't be produced sufficiently. SMN2 produces a small amount functional SMN protein due to substitution (C-T) in exon 7. SMA is classfied into five types (0-IV) based on age of onset, severity of motor decline and life expectancy. Type I (Werding-Hoffmann) is the most severe and primarily affects infants. Phenotypic variability in SMA patients is also associated with the copy number of the SMN2 gene. The copy number of SMN2 correlates with the severity of the disease. The SMN protein has a key regulator roles such as mRNA transport, RNA metabolism in neuronal cells. Currently, the main target for SMA treatment is to increase SMN protein level in motor neuron cells with small molecules, oligonucleotides, and gene replacement. Stem cell studies are performed as well for SMA treatment. FDA has approved three drugs in the SMA treatment since 2016. These drugs are nusinersen (oligonucleotide), onasemnogene abeparvovec- xioi (gene therapy), and risdiplam (SMN2 gene modifier). Early diagnosis has important role in drugs efficacy. Motor neuron dysfunctions may be reversible when SMN-dependent therapeutic approaches can be applied presymptomatically. Keywords Spinal muscular atrophy (SMA), survival motor neuron (SMN), nusinersen, onasemnogene abeparvovec-xioi, risdiplam Spinal muskuler atrofi (SMA), survival motor neuron (SMN1) genindeki delesyonlar veya mutasyonlarin neden oldugu otozomal resesif bir noromuskuler bir hastaliktir. Cocuk olumlerinin en yaygin kalitsal nedenidir. SMN1, tum okaryotik organizmalarin genomunda tek kopya olarak bulunur. Genomik duplikasyon ile ikinci bir gen SMN2 insanlarda ortaya cikmistir. Hastalarin yaklasik %95'i SMN1 geninin ekzon 7'sinde homozigot delesyonlara sahiptir. Bundan dolayi SMN proteini yeterli miktarda uretilemez. SMN2, ekzon 7'deki substitusyondan (C-T) dolayi kucuk miktarda fonksiyonel SMN proteini uretir. SMA; baslangic yasi, motor gerilemenin siddeti ve beklenen yasam suresine gore bes tip (0-IV) olarak siniflandirilmaktadir. Tip I (Werding-Hoffmann) en ciddi formudur ve ozellikle yenidoganlari etkilemektedir. SMA hastalarindaki fenotipik degiskenlik, SMN2 geninin kopya sayisi ile iliskilidir. SMN2'nin kopya sayisi hastaligin siddeti ile korelasyon gostermektedir. SMN proteini, noronal hucrelerde mRNA transportu, RNA metabolizmasi gibi anahtar duzenleyici rollere sahiptir. Gunumuzde SMA tedavisi icin ana hedef; kucuk molekuller, oligonukleotidler ve gen replasmani ile motor noronlarda SMN seviyesini artirmaktir. SMA tedavisi icin kok hucre calismalari da yapilmaktadir. FDA, 2016 yilindan beri SMA tedavisi icin uc yeni ilac onayladi. Bu ilaclar; nusinersen (oligonukleotit), onasemnogene abeparvovec-xioi (gen replasmani) ve risdiplam (SMN2 gen modulatoru)'dir. Ilaclarin etkililiginde erken tani onemli bir role sahiptir. SMN bagimli terapotik yaklasimlar presemptomatik olarak uygulandiginda motor noron disfonksiyonlari reversible olabilir. Anahtar kelimeler Spinal muskuler atrofi (SMA), survival motor noron (SMN), nusinersen, onasemnogene abeparvovec-xioi, risdiplam
  • Editor: Galenos Yayinevi Tic. Ltd
  • Idioma: Turco
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