Human endogenous retrovirus W in brain lesions: Rationale for targeted therapy in multiple sclerosis

Abstract

HERV-W was expressed in demyelinated lesions from MS brains, which were all positive for this endogenous pathogenic protein. Pronounced HERV-W immunoreactivity in active MS lesions was intimately associated with areas of active demyelination throughout the successive stages of lesion evolution in MS brains. Based on its pathogenic potential, this HERV-W (MSRV) endogenous toxin thus appears to be a novel therapeutic target in MS. It also has a unique positioning as an early and lifelong expressed pathogenic agonist, acting upstream the pathways in which dysregulated physiological effectors are usually targeted by present therapeutic strategies for MS.

The aliens inside us: HERV-W endogenous retroviruses and multiple sclerosis

“…7,13,15,34 HERV-W/MSRV/Syncytin-1 expression during MS therapy When MS patients undergo successful therapies, the expression of MSRV diminishes accordingly. In a longitudinal evaluation of MS patients, during efficacious therapy with interferon β, it was found that MSRV viremia fell rapidly below detection limits (the earliest effect was detected 48 hours after the first drug shot; 27 notably, a patient, after initial clinical and virological benefit, had MSRV rescue, preceding a strong disease progression and therapy failure.…”

An ancestral retroviral protein identified as a therapeutic target in type-1 diabetes

“…GNbAC1 is a humanized IgG4 antibody grafted with the 6 complementarity-determining region (CDRs) of an HERV-W-Env-neutralizing clonal hybridoma directed against the HERV-W protein encoded by MSRV-env clone (GenBank, AF331500-1; https://www.ncbi.nlm.nih.gov/genbank/), produced in CHO cells as a recombinant antibody under GMP conditions for therapeutic use. These custom antibodies have already been tested and published in peer-reviewed publications (24,25,30,35,50). GN_mAb_Env04 does not recognize the same epitope that GN_mAb_Env03.…”

“…GN_mAb_Env03 monoclonal antibody was developed by GeNeuro and has already been validated in several publications (24,25,30). GN_mAb_Env03 monoclonal antibody was used at a concentration of 5 μg/ml for the 77 slides.…”

“…Particularly, the envelope protein of HERV-W, HERV-W-Env, also named MSRV-Env, has been found elevated in sera of MS patients and its corresponding RNA in human peripheral blood mononuclear cells (PBMC) (24,29). HERV-W-Env has also been detected in infiltrated and resident macrophages in MS brain lesions (24,30). To date, 2 full-length envelope proteins from the HERV-W family have been described, a pathogenic protein named MSRV-Env from first MS isolates or HERV-W-Env and a physiologic protein named Syncytin-1, which is specifically involved in syncytiotrophoblast formation during placentation.…”

Human Endogenous Retroviruses

“…Another example, HERV-W was first retroelement associated with multiple sclerosis (MS) (Perron et al, 1997). After many years, it was proved that HERV-W RNA and proteins have been ubiquitously found in active MS lesions (van Horssen et al, 2016). Furthermore, HERV-W positivity is directly correlated with rapid diagnosis of MS (Sotgiu et al, 2010).…”