Rituximab levels in cerebrospinal fluid of patients with neurological autoimmune disorders

Petereit, Hela-Felicitas; Rubbert-Roth, Andrea

doi:10.1177/1352458508098268

Cited by 76 publications

(50 citation statements)

References 10 publications

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“…Interestingly, the CSF-blood ratio of GNbAC1 in one observation was 0.2% indicating blood-brain-barrier penetration of the mAb; this value is in line with other published values of CSF-blood ratio observed with mAbs administered to MS patients such as those of the anti-LINGO mAb BIIB033 (Tran et al, 2014) or rituximab (Petereit and Rubbert-Roth, 2009).…”

Section: Discussionsupporting

confidence: 88%

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: Discussionsupporting

confidence: 88%

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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show abstract

“…A study investigating the CSF concentration of rituximab after i.v. application in two MS patients (one with progressive disease) revealed 0.1 -0.25% of this antibody being present in the CSF 24 weeks after application [110]. More evidence comes from clinical trials with LINGO-1-IgG [111] and rHIgM22 antibody [112].…”

Section: Pharmacological Aspects Of Nogo-a-antibody Therapymentioning

confidence: 99%

Nogo-A antibodies enhance axonal repair and remyelination in neuro-inflammatory and demyelinating pathology

et al. 2017

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Two hallmarks of chronic multiple sclerosis lesions are the absence of significant spontaneous remyelination and primary as well as secondary neurodegeneration. Both characteristics may be influenced by the presence of inhibitory factors preventing myelin and neuronal repair. We investigated the potential of antibodies against Nogo-A, a well-known inhibitory protein for neuronal growth and plasticity, to enhance neuronal regeneration and remyelination in two animal models of multiple sclerosis. We induced a targeted experimental autoimmune encephalomyelitis (EAE) lesion in the dorsal funiculus of the cervical spinal cord of adult rats resulting in a large drop of skilled forelimb motor functions. We subsequently observed improved recovery of forelimb function after anti-Nogo-A treatment. Anterograde tracing of the corticospinal tract revealed enhanced axonal sprouting and arborisation within the spinal cord gray matter preferentially targeting pre-motor and motor spinal cord laminae on lesion level and above in the anti-Nogo-A-treated animals. An important additional effect of Nogo-A-neutralization was enhanced remyelination observed after lysolecithin-induced demyelination of spinal tracts. Whereas remyelinated fiber numbers in the lesion site were increased several fold, no effect of Nogo-A-inhibition was observed on oligodendrocyte precursor proliferation, migration, or differentiation. Enhancing remyelination and promoting axonal regeneration and plasticity represent important unmet medical needs in multiple sclerosis. Anti-Nogo-A antibodies hold promise as a potential new therapy for multiple sclerosis, in particular during the chronic phase of the disease when neurodegeneration and remyelination failure determine disability evolution. Key pointsSolid pre-clinical data suggests Nogo-A-neutralization as a potential therapeutic approach for neuroinflammatory and demyelinating pathology. Nogo-A-antibodies are now in early clinical development for multiple sclerosis (MS). Their potential to boost axonal regeneration and compensatory fiber growth as well as myelin repair makes them an attractive candidate to treat also progressive MS in which neurodegeneration and chronic demyelination are hallmarks. AbstractMost of the current therapies as well as many of the clinical trials for Multiple Sclerosis (MS) target the inflammatory autoimmune processes, but less than 20% of all clinical trials investigate potential therapies for the chronic progressive disease stage of MS. The latter is responsible for the steadily increasing disability in many patients, and there is an urgent need for novel therapies that protect nervous system tissue and enhance axonal growth and/or remyelination. As outlined in this review, solid pre-clinical data suggest neutralization of the neurite outgrowth inhibitor Nogo-A as a potential new way to achieve both, axonal and myelin repair. Several phase I clinical studies with anti-Nogo-A antibodies have been conducted in different disease paradigms including MS and spinal cord injur...

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“…However, although antibodies do not pass through an intact BBB, their trafficking may be possible when this barrier is inflamed and damaged as in the case of active CNS disease [51]. This may provide a possible explanation of the efficacy of PLEX in our study, which included patients with active disease and recent deterioration (ie with a compromised BBB).…”

Section: Discussionmentioning

confidence: 95%

Clinical Efficacy of Plasma-Exchange in Patients with Progressive forms of Multiple Sclerosis and NMO-Spectrum Disease

Petrou¹,

Ben‐Hur²,

Vaknin‐Dembinsky³

et al. 2016

J Mult Scler (Foster City)

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Rituximab levels in cerebrospinal fluid of patients with neurological autoimmune disorders

Abstract: Rituximab remains detectable within the CSF after i.v. application for up to 24 weeks. Furthermore, levels of rituximab in CSF correlate significantly with the integrity of the blood CSF barrier.

Cited by 76 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

Nogo-A antibodies enhance axonal repair and remyelination in neuro-inflammatory and demyelinating pathology

Clinical Efficacy of Plasma-Exchange in Patients with Progressive forms of Multiple Sclerosis and NMO-Spectrum Disease

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