Pharmacological treatment of Duchenne and Becker muscular dystrophies
Absztrakt
Currently, there is no cure for muscular dystrophy. Treatment is generally aimed at controlling the onset of symptoms to maximize the quality of life. Medical therapy contains exon-skipping agents, utrophin upregulation, histone deacetylase inhibitors, corticosteroids, myostatin blockers, ataluren, and tyrosinekinase inhibitors. Exon skipping uses antisense oligonucleotides as a treatment for genetic diseases. The antisense oligonucleotides used for exon skipping are designed to bypass premature stop codons in the target RNA and restore reading frame disruption. Utrophin upregulation results improved sarcolemmal stability and prevents dystrophic pathology through a significant reduction of regeneration, necrosis and fibrosis.
Leírás
Kulcsszavak
AAV – adeno-associated viruses, Ad – adenoviruses, ADSCs – adipose derived stem cells, AFOs – ancle foot orthoses, BMD – Becker muscular dystrophy, CVS – chorion villus sampling, DAPC – dystrophin-associated protein complex, DMD – Duchenne muscular dystrophy, EMA – European Medical Agency, EMG – electromyography, ES – human embryonic, FAPs – fibro-adipogenic progenitors, HDACi – histone deacetylase inhibitor, IA - intraarterial, IM - intamuscular, iPSCs – induced pluripotent stem cells, IV – intravenous, KAFOs – knee ankle foot orthoses, LBM – lean body mass, MCK – muscle creatine kinase, MDSCs – muscle derived stem cells, MMT – manual muscle testing, MSCs – mesenchymal stem cells, PMO – phosphorodiamidate morpholino oligomer, PS – phosphorothioate, rhBGN – recombinant human diglycan, ROM – range of motion, ROS – reactive-oxygen species, SCs – satellita cells, SP cells – side population cells, TLRs – troll-like receptorsTMV – tight muscle volume