Inhibition of multiple sclerosis–associated retrovirus as biomarker of interferon therapy

Abstract

The authors performed a longitudinal evaluation of multiple sclerosis (MS) patients, during 1 year of therapy with interferon-beta (IFN-beta), by clinical examination and detection of presence in the blood and viral load of MS-associated retrovirus (MSRV), by MSRVenv-specific, fully quantitative, real time reverse transcriptase-polymerase chain reaction (RT-PCR). MSRV load in the blood was directly related to MS duration and fell below detection limits within 3 months of IFN therapy; one patient had strong progression, accompanied by total MSRV rescue. These findings suggest that evaluation of plasmatic MSRV could be considered the first prognostic marker for the individual patient, to monitor disease progression and therapy outcome.

A phase IIa randomised clinical study of GNbAC1, a humanised monoclonal antibody against the envelope protein of multiple sclerosis-associated endogenous retrovirus in multiple sclerosis patients

“…This suggests that neutralising the MSRV-Env protein also down-regulates the expression of the corresponding endogenous retroviral genome. Moreover two reference MS treatments induce similar responses: interferon beta induces a decrease of MSRV-Env RNA measured by RT-PCR observed already at three months 15 while natalizumab induces a decrease of MSRV-Env mRNA, measured by RT-PCR, observed later after six months of treatment. 16 This pharmacodynamic response paralleling the response observed with MS treatments natalizumab and interferon beta is promising in terms of therapeutic efficacy.…”

Expression of HERV-Fc1, a Human Endogenous Retrovirus, Is Increased in Patients with Active Multiple Sclerosis

“…Nevertheless, a significant decrease in anti-Env antibody reactivity for HERV-H and HERV-W as a consequence of IFN-␤ therapy, closely linked to the efficacy of therapy, has been reported (51). Furthermore, there are also suggestions that IFN therapy caused prompt and complete inhibition of MSRV circulation (38).…”

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

“…30 25 (b) Progression to the secondary progressive (SPMS) course within 10 years of early RRMS patients, according to presence/absence of HERV-W/MSRV genomic RNA in the spinal fluids at study entry; for details, see Sotgiu et al 26 (c) Circulating HERV-W/MSRV and disease outcome of MS patients, after 12 months of efficacious therapy with interferon β or natalizumab. To compare the two studies, 27,28 the original data were normalized to the mean HERV-W/MSRV RNA values at study entry, taken as 100%. In the interferon β study, 27 virionic HERV-W/ MSRVenv RNA was evaluated, by real-time quantitative RT-PCR amplification, and post-therapy levels were below detection limits of the assay (<10 copies/reaction).…”