Monitoring Biomarker Study in Becker Muscular Dystrophy using Data Independent Acquisition LC-MS/MS

ABSTRACT: Becker muscular dystrophy (BMD) is a rare and heterogenous form of dystrophinopathy caused by reduced expression of altered dystrophin protein. Gene therapies and exon-skipping therapies for the more severe form of dystrophinopathy, Duchenne muscular dystrophy (DMD), assume that disease progression can be slowed by promoting the expression of truncated dystrophin comparable to what occurs in BMD patients. Several studies have identified potential progression biomarkers for DMD and hypothesised in their usefulness in monitoring pharmacodynamic response in therapeutic clinical trials aiming to restore gene expression. However, knowledge of progression changes of blood proteome in BMD is lacking. In this study, we aimed at exploring differences in proteomic changes between DMD and BMD as well as explore what proteins relate to functional performance in BMD patients in a prospective longitudinal 3-year study. Serum from 34 BMD patients and 19 DMD patients was analysed using Data Independent Acquisition Tandem Mass Spectrometry (DIA-MS). Linear mixed effects models identified 20 proteins with altered longitudinal signatures between DMD and BMD, among these CKM, PKM, FGG, LDHB and A2M. Furthermore, several proteins related to innate immune response were found related to functional performance in BMD patients and A2M displayed an altered time-dependent decline in relation to dystrophin expression in the tibialis anterior muscle.

ORGANISM(S): Homo Sapiens

SUBMITTER: David Kotol  

PROVIDER: PXD054253 | panorama | Fri Oct 31 00:00:00 GMT 2025

REPOSITORIES: PanoramaPublic