Antibody Treatment Shows Promise in Reversing Endogenous Retrovirus Damage in Multiple Sclerosis Models

A new preprint study on bioRxiv reports that a neutralizing antibody targeting the HERV-W envelope (ENV) protein can ameliorate neurodegeneration and promote remyelination in transgenic mice engineered to express this human-specific retroviral protein. The human endogenous retrovirus type W has previously been identified as a neuropathological factor in multiple sclerosis, where it disrupts myelin repair and drives microglia and astroglia toward neurotoxic states. In the mouse model, repeated intraperitoneal injections of the anti-ENV antibody led to accelerated oligodendroglial differentiation, enhanced remyelination, axonal protection, and reduced serum levels of neurofilament light chain, a biomarker of neuronal damage. Neurotoxic microglial traits were diminished while homeostatic microglial parameters were stabilized, and astroglia similarly shifted toward regenerative rather than toxic phenotypes, creating a less hostile environment for repair. These results align with early clinical trial data from Temelimab, a humanized anti-ENV antibody, which had provided indirect evidence of HERV-W's anti-regenerative and neurodegenerative role in MS patients. The study is particularly relevant to progression independent of relapse activity (PIRA), a form of MS worsening that lacks effective treatments and is thought to involve smoldering inflammatory and degenerative processes. The authors conclude that HERV-W neutralization represents a mechanistically grounded therapeutic strategy for addressing this underserved aspect of MS pathology.