Seroconversion of JCV antibodies is strongly associated to natalizumab therapy

Fragoso, Yára Dadalti; Brooks, Joseph Bruno Bidin; Eboni, Audred C. Biondo; Fezer, Leticia; Gama, Paulo Diniz da; Gomes, Sidney; Gonçalves, Marcus Vinícius Magno; Machado, Suzana Nunes; Morales, Rogerio Rizo; Pimentel, Maria Lúcia Vellutini; Ruocco, Heloisa Helena; Santos, Gutemberg Augusto Cruz dos; Scherpenhuijzen, Simone; Sousa, Nise Alessandra C.

doi:10.1016/j.jocn.2018.10.128

Cited by 4 publications

(1 citation statement)

References 12 publications

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“…Natalizumab (Tysabri) is a monoclonal antibody against very late activating antigen (VLA)-α4 integrin and can bind to a majority of leukocytes, impeding cross over through the blood brain barrier into the CNS, thereby diminishing the aberrant heightened immune surveillance and inflammation (Stuve et al, 2006). However, use of Natalizumab in patients infected with John Cunningham virus (JCV) can result in progressive multifocal leukoencephalopathy (PML) in a subset of patients (Clerico et al, 2017;Ho et al, 2017;Fragoso et al, 2019;Ryerson et al, 2019). JCV is an opportunistic virus causing oligodendrocyte destruction, demyelination, and eventually a detrimental inflammatory reaction.…”

Section: Ms Patient Therapeuticsmentioning

confidence: 99%

Pre-clinical and Clinical Implications of “Inside-Out” vs. “Outside-In” Paradigms in Multiple Sclerosis Etiopathogenesis

Titus

Chen

Podojil

et al. 2020

Front. Cell. Neurosci.

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Multiple Sclerosis (MS) is an immune-mediated neurological disorder, characterized by central nervous system (CNS) inflammation, oligodendrocyte loss, demyelination, and axonal degeneration. Although autoimmunity, inflammatory demyelination and neurodegeneration underlie MS, the initiating event has yet to be clarified. Effective disease modifying therapies need to both regulate the immune system and promote restoration of neuronal function, including remyelination. The challenge in developing an effective long-lived therapy for MS requires that three disease-associated targets be addressed: (1) self-tolerance must be re-established to specifically inhibit the underlying myelin-directed autoimmune pathogenic mechanisms; (2) neurons must be protected from inflammatory injury and degeneration; (3) myelin repair must be engendered by stimulating oligodendrocyte progenitors to remyelinate CNS neuronal axons. The combined use of chronic and relapsing remitting experimental autoimmune encephalomyelitis (C-EAE, R-EAE) ("outside-in") as well as progressive diphtheria toxin A chain (DTA) and cuprizone autoimmune encephalitis (CAE) ("inside-out") mouse models allow for the investigation and specific targeting of all three of these MSassociated disease parameters. The "outside-in" EAE models initiated by myelin-specific autoreactive CD4 + T cells allow for the evaluation of both myelin-specific tolerance in the absence or presence of neuroprotective and/or remyelinating agents. The "inside-out" mouse models of secondary inflammatory demyelination are triggered by toxin-induced oligodendrocyte loss or subtle myelin damage, which allows evaluation of novel therapeutics that could promote remyelination and neuroprotection in the CNS. Overall, utilizing these complementary pre-clinical MS models will open new avenues for developing therapeutic interventions, tackling MS from the "outside-in" and/or "inside-out".

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