Identificación de la proteína Desmina en mioblastos de paciente con LGMDD2, tratados con oligonucleótidos antisentido bloqueadores del splicing alternativo

Abstract

Abstract: Limb-girdle muscular dystrophy type D2, caused by dominant mutations in the TNPO3 gene, is responsible for cytoskeletal disorganization and poor muscle regeneration. This study was based on evaluating the therapeutic potential of four splicing-blocking antiseous oligonucleotides (SSOs: SSO 1a, 1b, 2a, 3a) to rescue the pathological phenotype in myoblasts of patients with this condition. The expression and organization of desmin by immunofluorescence were analyzed and the diameter of the myotubes and the cell fusion index were quantified. The results showed that SSOs 1b and 2a significantly affect the diameter of the moiotubes, reaching comparable values, even higher than healthy controls. On the other hand, SSO 3a was the only treatment that significantly improved the cell fusion index. These findings indicate that specific modulation of TNPO3 splicing through ASOs constitutes a considerable strategy in gene therapy to correct or improve the structural and morphological alterations in LGMDD2.