Targeting Secondary Muscle Atrophy to Enhance Motor Recovery in Experimental Autoimmune Neuritis

ABSTRACT: Secondary muscle atrophy due to neuronal denervation is a key determinant of poor functional recovery in immune-mediated neuropathies, even after resolution of inflammation. Activin II receptors (ActIIRs) are central mediators of muscle atrophy, and their inhibition has shown variable efficacy in primary myopathies. We investigated the therapeutic potential of ActIIR inhibition in promoting motor recovery in immune-mediated neuropathies using the experimental autoimmune neuritis (EAN) model in Lewis rats. Motor performance was evaluated through a composite of clinical neuritis scoring, grip strength testing, and balance beam performance combined with kinematic gait analysis. High-dose antibody treatment significantly improved motor outcome. This improvement was not associated with changes in peripheral nerve inflammation or remyelination but correlated with preservation of muscle fiber size. Muscle proteomic analysis revealed modulation of the FoxO signaling pathway and reduced expression of the atrophy-related E3 ligases Atrogin-1 and MuRF1. These findings indicate that ActIIR inhibition prevents secondary muscle atrophy and enhances motor recovery in autoimmune neuritis. Targeting ActIIR signaling may represent a promising therapeutic strategy to improve motor outcomes in patients with immune-mediated neuropathies.

INSTRUMENT(S):

ORGANISM(S): Rattus Rattus (black Rat)

TISSUE(S): Muscle

SUBMITTER: Proteomics Facility  

LAB HEAD: Prof. Michael Schroeter

PROVIDER: PXD070456 | Pride | 2026-04-13

REPOSITORIES: Pride