Pathological and protective effects of tumor necrosis factor-alpha in multiple sclerosis

Смагина, И. В.; Ельчанинова, С. А.; Palashchenko, A. S.; Galaktionova, L P

doi:10.17116/jnevro20191191014

Cited by 1 publication

(2 citation statements)

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“…Tumor necrosis factor-alpha (TNF alpha) is an immunomodulatory cytokine involved in physiological and pathological processes in the CNS [3]. However, its role in the pathogenesis of MS is complex due to its contradictory effects [4].…”

Section: Introductionmentioning

confidence: 99%

“…TNF-alpha inhibitors are currently used as an efficient therapeutic choice in many autoimmune and inflammatory diseases [4]. Several TNF alpha-blockers have been approved by the FDA, including etanercept, infliximab, golimumab, certolizumab, and adalimumab [3]. However, many CNS demyelination events have been reported in patients receiving anti-TNF drugs [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tumor Necrosis Factor Alpha Blockade and Multiple Sclerosis: Exploring New Avenues

Zahid¹,

Busmail²,

Penumetcha³

et al. 2021

Cureus

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Multiple sclerosis (MS) is the most common disabling disease of the central nervous system (CNS) with a progressive neurodegenerative pattern. It is characterized by demyelination of white matter in CNS and apoptosis of oligodendrocytes. Tumor necrosis factor (TNF) alpha is a major cytokine in the pathogenesis of MS. However, the failure of TNF alpha inhibitors in preclinical and clinical trials disapproved of their use in MS patients. Nevertheless, failures and misses sometimes open avenues for new hits. In the later years, it was discovered that TNF signaling is mediated via two different receptors, TNFR1 and TNFR2, both of which have paradoxical effects. TNFR1 mediates demyelination and apoptosis, while TNFR2 promotes remyelination and neuroprotection. This explained the cause of the failure of non-selective TNF alphablockers in MS. It also enlightened researchers that repurposing the previously formulated non-selective TNF alpha-blockers using a receptor-selective approach could lead to discovering novel biologic agents with a broader spectrum of indications and better safety profiles. This review focuses on a novel premier TNFR1 blocker, atrosab, which has been tested in animal models of MS, experimental autoimmune encephalomyelitis (EAE), where it demonstrated a reduction in symptom severity. The early promise shown by atrosab in preclinical studies has given us hope to find another revolutionary drug for MS in the future. Clinical trials, which will finally decide whether this drug can be used as a better therapeutic agent for MS or not, are still going on, but currently, there is no approved evidence regarding efficacy of these agents in treating MS.

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Section: Introductionmentioning

confidence: 99%