Research: Targeting MS Associated Retrovirus

Curtin et al. GNbAC1, a Humanized Monoclonal Antibody Against the Envelope Protein of Multiple Sclerosis-Associated Endogenous Retrovirus: A First-in-Humans Randomized Clinical Study. Clin Ther. 2012 Nov 28. doi:pii: S0149-2918(12)00649-2. 10.1016/j.clinthera.2012.11.006.

BACKGROUND: Human endogenous retrovirus (HERV) genes represent about 8% of the human genome. A member of the HERV family W, the Multiple Sclerosis-Associated Retrovirus (MSRV) gene, encodes an envelope protein (Env), which can activate a proinflammatory and autoimmune cascade through its interaction with Toll-like receptor 4. Due to its proinflammatory property and an inhibitory effect on oligodendrocyte precursor cell differentiation, the MSRV-Env protein could play a crucial role in the pathogeny of multiple sclerosis. GNbAC1 is a humanized monoclonal antibody of the immunoglobulin G4 type, which is directed against MSRV-Env. After validation of the MSRV-Env as a therapeutic target in preclinical experimental models, a clinical development program was initiated.

OBJECTIVE: This study evaluated the safety profile, pharmacokinetic parameters, and immunogenicity of GNbAC1 in healthy male volunteers.

METHODS: In this first-in-humans, Phase I, randomized, double-blind, placebo-controlled, dose-escalation study, each subject received a single dose of IV GNbAC1 0.0025, 0.025, 0.15, 0.6, 2, or 6 mg/kg or inactive vehicle (placebo), infused over 1 hour. Tolerability and other laboratory parameters were observed, and regular blood sampling was performed, to study the pharmacokinetic properties and immunogenicity of this monoclonal antibody.

RESULTS: A total of 33 male subjects (mean age, 44 years) completed the study. GNbAC1 was well tolerated after dosing in all subjects and in each dose cohort. Only minor and nonspecific adverse events (AEs) were recorded; no serious AEs were reported. Pharmacokinetic data show a dose-linear pharmacokinetic profile. The mean elimination half-life ranged between 19 and 26 days, with therapeutically efficient concentrations maintained over a 4-week periods at doses of 2 and 6 mg/kg. No emergence of anti-GNbAC1 antibodies were detected after dosing in any subject over the entire observation period of 64 days.

CONCLUSIONS: In these healthy male subjects, the safety and pharmacokinetic profiles of GNbAC1 appeared favorable. These findings are expected to allow for the launch of a Phase II development program for this innovative therapeutic approach in patients with multiple sclerosis. ClinicalTrials.gov identifier: NCT01699555.


It looks like the Charcot project has a new running mate, this agent aims to target an endogenous retrovirus. The challenge is will it work? Where would it work, as an antibody will struggle to get into the brain to mop-up shed virus? and does it need to get inside cells to act?. The phase II is now recruiting NCT01639300. 

If active, a vaccine would be the easier strategy or maybe a small drug which is the Charcot Project Approach. Something on that fromProf G Dow Under Soon.

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