Identificación de la proteína desmina en mioblastos de paciente con LGMDD2, tratados con oligonucleótidos tipo GapmeRs

Abstract

Abstract: Limb-girdle muscular dystrophy type D2 (LGMD D2) is a rare inherited disorder caused by mutations in the TNPO3 gene, which encodes the TNPO3 protein involved in mRNA splicing and metabolism. This mutation leads to progressive muscle weakness and atrophy of proximal and distal muscles, generalized contractures, and skeletal deformities. In this study, an in vitro cell model was used to evaluate the therapeutic potential of four types of GapmeRs that modulate the altered gene expression in LGMD D2. Myogenic morphological parameters such as myoblast fusion index and myotube diameter were analyzed using direct immunofluorescence for desmin protein. Control (healthy) cells showed adequate myogenic differentiation, reflected in high fusion indices and larger myotube diameters. In contrast, LGMD D2 cells exhibited alterations in all evaluated parameters. Treatments with GapmeRs allowed a partial recovery of these parameters, with significant improvements observed compared to the untreated LGMD D2 group, although without reaching the levels of the healthy control.