The neutralizing antibody GNbAC1 abrogates HERV-W envelope protein-mediated oligodendroglial maturation blockade

Kremer, David; Förster, Moritz; Schichel, Tanja; Göttle, Peter; Hartung, Hans‐Peter; Perron, Hervé; Küry, Patrick

doi:10.1177/1352458514560926

Cited by 58 publications

(60 citation statements)

References 10 publications

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“…Pre-clinical studies showed that GNbAC1 neutralizes the MSRV-Env target (Rolland et al, 2006;Kremer et al, 2014). GNbAC1 had been studied first in a phase I clinical trial in 33 healthy subjects, showing a good safety as well as a linear pharmacokinetics (Curtin et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

A phase IIa randomized clinical study testing GNbAC1, a humanized monoclonal antibody against the envelope protein of multiple sclerosis associated endogenous retrovirus in multiple sclerosis patients — A twelve month follow-up

Derfuss

Curtin

Guebelin

et al. 2015

Journal of Neuroimmunology

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GNbAC1 is a humanized monoclonal antibody targeting MSRV-Env, an endogenous retroviral protein, which is expressed in multiple sclerosis (MS) lesions, is pro-inflammatory and inhibits oligodendrocyte precursor cell differentiation. This paper describes the open-label extension up to 12 months of a trial testing GNbAC1 in 10 MS patients at 2 and 6 mg/kg. The primary objective was to assess GNbAC1 safety, and other objectives were pharmacokinetic and pharmacodynamic assessments. During the extended study, no safety issues occurred in the 8 remaining patients. No anti-GNbAC1 antibodies were detected. GNbAC1 appears well tolerated.

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Section: Introductionmentioning

confidence: 99%

A phase IIa randomized clinical study testing GNbAC1, a humanized monoclonal antibody against the envelope protein of multiple sclerosis associated endogenous retrovirus in multiple sclerosis patients — A twelve month follow-up

Derfuss

Curtin

Guebelin

et al. 2015

Journal of Neuroimmunology

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“…Yet the precise association between HIV and MS still remains unresolved. For enhanced understanding of the basic mechanisms behind the role of Recent reports have revealed that MS patients treated with GNbAC1 showed signs of improvement, which suggests neuroprotective attributes of GNbAC1, thus supporting its potential as a safe, promising and better long-term treatment option for MS patients [41][42][43].…”

Section: Hiv Connection With Msmentioning

confidence: 99%

Human Immunodeficiency Virus and Multiple Sclerosis Risk: Probing for a Connection

Khan

Zahoor²,

Haq³

2015

J Mult Scler

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Multiple Sclerosis (MS) is a chronic autoimmune inflammatory disease of the nervous system, with intense genetic and environmental background. Its etiology is poorly understood and likely multifactorial but its epidemiology has been intensively studied. This complex disease displays heterogeneity in terms of geographic and genetic influences on incidence, insinuating an effect of local unknown environmental factors on its development. Among numerous potential factors putatively involved in the etiopathogenesis of MS, retroviruses appear to influence MS. The intent of this review is to highlight the association between human immunodeficiency virus (HIV) and the risk of developing MS while at the same time providing an overview of the insights gleaned from different studies. HIV infection is associated with a reduced risk of MS development, and perhaps, appears to be another wedge of the MS conundrum. The probable mechanisms for this relationship may be suppression of the immune system and/or antiretroviral drug therapy. While highlighting the relevance of antiretroviral medications as potential future alternatives for the effective treatment of MS, this review provides an impetus for further studies. We conclude that studies in this milieu hitherto are insufficient, and there is need for an upsurge in molecular epidemiological and clinical studies, with focus on the mechanism behind the impact of HIV/antiretroviral drugs on MS. Such inquiry could precisely establish the causes for associations between HIV and MS, perhaps impacting treatment options for both.

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“…9 Another effect of MSRV-Env is the blockade of the oligodendrocyte differentiation necessary for the remyelination process, also mediated by an interaction with TLR4 on oligodendrocyte precursor cells (OPCs). 10 Based on the ability of MSRV-Env to activate the innate immune system and given its direct toxicity on OPCs, MSRV-Env is a relevant therapeutic target for MS.…”

mentioning

confidence: 99%

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

et al. 2014

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The neutralizing antibody GNbAC1 abrogates HERV-W envelope protein-mediated oligodendroglial maturation blockade

Abstract: Beyond immune cell modulation, this monoclonal antibody may therefore help to overcome the oligodendroglial differentiation blockade in MS.

Cited by 58 publications

References 10 publications

A phase IIa randomized clinical study testing GNbAC1, a humanized monoclonal antibody against the envelope protein of multiple sclerosis associated endogenous retrovirus in multiple sclerosis patients — A twelve month follow-up

A phase IIa randomized clinical study testing GNbAC1, a humanized monoclonal antibody against the envelope protein of multiple sclerosis associated endogenous retrovirus in multiple sclerosis patients — A twelve month follow-up

Human Immunodeficiency Virus and Multiple Sclerosis Risk: Probing for a Connection

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

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