Abstract
The current landscape of therapeutics designed to treat multiple sclerosis (MS) and its pathological sequelae is saturated with drugs that modify disease course and limit relapse rates. While these small molecules and biologicals are producing profound benefits to patients with reductions in annualized relapse rates, the repair or reversal of demyelinated lesions with or without axonal damage, remains the principle unmet need for progressive forms of the disease. Targeting the extracellular pathological milieu and the signaling mechanisms that drive neurodegeneration are potential means to achieve neuroprotection and/or repair in the central nervous system of progressive MS patients. The Nogo-A receptor-dependent signaling mechanism has raised considerable interest in neurological disease paradigms since it can promulgate axonal transport deficits, further demyelination, and extant axonal dystrophy, thereby limiting remyelination. If specific therapeutic regimes could be devised to directly clear the Nogo-A-enriched myelin debris in an expedited manner, it may provide the necessary CNS environment for neurorepair to become a clinical reality. The current review outlines novel means to achieve neurorepair with biologicals that may be directed to sites of active demyelination.
Highlights
Multiple sclerosis (MS) is a neurodegenerative disorder predominantly affecting the femaleCaucasian population with median incidence less than 40 years of age
The radiologically isolated syndrome (RIS) classification was included by the advisory committee commissioned by the National Multiple Sclerosis Society (NMSS) because it was felt that due to the advancement in magnetic resonance imaging (MRI) technology, a greater frequency in patients without clinical signs or symptoms of MS were being identified under routine MRI
This study suggests myelin plasticity in ngr1−/− mice, highlighting another potential role for Nogo receptor 1 (NgR1) during development and axo-glial maintenance in the adults [64]
Summary
Multiple sclerosis (MS) is a neurodegenerative disorder predominantly affecting the female. Its chief clinical manifestation is demyelination in the central nervous system (CNS) including the brain, spinal cord, and optic nerve. The pathogenesis of MS manifests as an acute and chronic inflammatory mediated demyelination of the CNS [1]. While currently available treatments are based on immunomodulatory therapies, that affect the inflammation status and sequelae of the patients diagnosed with MS, with specific or indirect mechanisms of action to suppress T and B cells, monocytes, and the innate immune cells, there still remains a significant unmet medical need to prevent longstanding demyelination and promote neural repair through remyelination. The pathogenesis of MS will be discussed thoroughly including mechanistic aspects. Cells 2019, 8, 1 and under clinical trial will be reviewed and a novel intervention of delivering a therapeutic protein to enhance recovery in MS will be discussed with existing evidence
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