In neuromuscular diseases of different pathogenic origins, there is growing evidence of a close interaction between the immune system, the nerve and the muscle. The aim of this review, involving researchers from the Institute of Myology and its partner FIOCRUZ in Brazil, is to analyse this phenomenon more closely in Duchenne muscular dystrophy (DMD) and amyotrophic lateral sclerosis (ALS).
The authors highlight the complexity of cellular and molecular interactions involving the immune system in neuromuscular diseases, as exemplified by DMD and ALS. They describe the different types of cell-mediated interactions, such as the production of cytokines and chemokines, as well as cell-matrix and cell-cell interactions between T lymphocytes and other immune cells, which target muscle or nerve tissue cells. Most of these interactions occur via ligand-receptor binding and subsequent signal transduction cascades, at distinct levels of specificity.
The complexity of the system revealed by this work can be seen as a window of opportunity to design therapeutic strategies (including using synthetic molecules, cell and gene therapy, as well as immunotherapy) by acting on one or more targets (Combined Therapies). With this in mind, the researchers are analysing ongoing clinical trials using VLA-4 inhibition in DMD, already proposed as biomarkers in a previous study already involving the Institute of Myology and FIOCRUZ, and in ALS, focusing on regulatory T cells. These trials both showed promising results.
