scholarly journals The Salvinorin Analogue, Ethoxymethyl Ether Salvinorin B, Promotes Remyelination in Preclinical Models of Multiple Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Kelly F. Paton ◽  
Katharina Robichon ◽  
Nikki Templeton ◽  
Lisa Denny ◽  
Afnan Al Abadey ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Side Effects ◽  
Immune Cell ◽  
Kappa Opioid Receptor ◽  
Demyelinating Diseases ◽  
Dependent Manner ◽  
Preclinical Models ◽  
The Central Nervous System

Multiple sclerosis is a neurodegenerative disease associated with demyelination and neuroinflammation in the central nervous system. There is an urgent need to develop remyelinating therapies to better treat multiple sclerosis and other demyelinating diseases. The kappa opioid receptor (KOR) has been identified as a potential target for the development of remyelinating therapies; however, prototypical KOR agonists, such as U50,488 have side effects, which limit clinical use. In the current study, we investigated a Salvinorin A analog, ethoxymethyl ether Salvinorin B (EOM SalB) in two preclinical models of demyelination in C57BL/6J mice. We showed that in cellular assays EOM SalB was G-protein biased, an effect often correlated with fewer KOR-mediated side effects. In the experimental autoimmune encephalomyelitis model, we found that EOM SalB (0.1–0.3 mg/kg) effectively decreased disease severity in a KOR-dependent manner and led to a greater number of animals in recovery compared to U50,488 treatment. Furthermore, EOM SalB treatment decreased immune cell infiltration and increased myelin levels in the central nervous system. In the cuprizone-induced demyelination model, we showed that EOM SalB (0.3 mg/kg) administration led to an increase in the number of mature oligodendrocytes, the number of myelinated axons and the myelin thickness in the corpus callosum. Overall, EOM SalB was effective in two preclinical models of multiple sclerosis and demyelination, adding further evidence to show KOR agonists are a promising target for remyelinating therapies.

Demyelinating disorders of the central nervous system

2010 ◽  
pp. 4948-4963
Author(s):  
Siddharthan Chandran ◽  
Alastair Compston
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Acute Disseminated Encephalomyelitis ◽  
Demyelinating Diseases ◽  
Demyelinating Disorder ◽  
System P ◽  
The Central Nervous System ◽  
Demyelinating Disorders ◽  
Brain And Spinal Cord

Clinicians suspect demyelination when episodes reflecting damage to white matter tracts within the central nervous system occur in young adults. The paucity of specific biological markers of discrete demyelinating syndromes places an emphasis on clinical phenotype—temporal and spatial patterns—when classifying demyelinating disorders. The diagnosis of multiple sclerosis, the most common demyelinating disorder, becomes probable when these symptoms and signs recur, involving different parts of the brain and spinal cord. Other important demyelinating diseases include post-infectious neurological disorders (acute disseminated encephalomyelitis), demyelination resulting from metabolic derangements (central pontine myelinosis), and inherited leucodystrophies that may present in children or in adults. Accepting differences in mechanism, presentation, and treatment, two observations can usefully be made when classifying demyelinating disorders. These are the presence or absence of inflammation, and the extent of focal vs. diffuse demyelination. Multiple sclerosis is prototypic for the former, whereas dysmyelinating disorders, such as leucodystrophies are representative of the latter....

scholarly journals New oligodendrocytes exhibit more abundant and accurate myelin regeneration than those that survive demyelination

2020 ◽  
Author(s):  
Sarah A Neely ◽  
Jill M Williamson ◽  
Anna Klingseisen ◽  
Lida Zoupi ◽  
Jason J Early ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Neuronal Cell ◽  
Live Imaging ◽  
Therapeutic Strategies ◽  
Demyelinating Diseases ◽  
Neuronal Cell Bodies ◽  
The Central Nervous System

Regeneration of myelin (remyelination) in the central nervous system (CNS) has long been thought to be principally mediated by newly generated oligodendrocytes, a premise underpinning therapeutic strategies for demyelinating diseases, including multiple sclerosis (MS). Recent studies have indicated that oligodendrocytes that survive demyelination can also contribute to remyelination, including in MS, but it is unclear how remyelination by surviving oligodendrocytes compares to that of newly generated oligodendrocytes. Here we studied oligodendrocytes in MS, and also imaged remyelination in vivo by surviving and new oligodendrocytes using zebrafish. We define a previously unappreciated pathology in MS, myelination of neuronal cell bodies, which is recapitulated during remyelination by surviving oligodendrocytes in zebrafish. Live imaging also revealed that surviving oligodendrocytes make very few new sheaths, but can support sheath growth along axons. In comparison, newly made oligodendrocytes make abundant new sheaths, properly targeted to axons, and exhibit a much greater capacity for regeneration.

Diagnosis of Multiple Sclerosis

2021 ◽  
pp. 540-547
Author(s):  
W. Oliver Tobin
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Demyelinating Disease ◽  
Acute Disseminated Encephalomyelitis ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Spectrum Disorder ◽  
Demyelinating Diseases ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
The Central Nervous System

Multiple sclerosis is the most common idiopathic inflammatory demyelinating disease of the central nervous system (CNS), with a prevalence of 1 in 500 to 1 in 2,000 people, depending on geography and various other factors. Idiopathic inflammatory demyelinating diseases are a group of related disorders that include acute disseminated encephalomyelitis, neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein–immunoglobulin G–associated CNS demyelinating disease.

Pathologic Factors and Spectrum of Central Nervous System Inflammatory Demyelinating Diseases

2021 ◽  
pp. 531-539
Author(s):  
Claudia F. Lucchinetti ◽  
Yong Guo
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Inflammatory Process ◽  
Demyelinating Disease ◽  
Autoimmune Disorder ◽  
Demyelinating Diseases ◽  
Autoreactive T Cells ◽  
Common Cause ◽  
The Central Nervous System

Multiple sclerosis (MS) is the most common cause of nontraumatic disability in young adults. It is a chronic inflammatory demyelinating disease of the central nervous system. Traditionally, MS has been considered an autoimmune disorder consisting of myelin autoreactive T cells that drive an inflammatory process, leading to secondary macrophage recruitment and subsequent myelin destruction. However, accumulating data based on increasing numbers of probes that can be effectively applied to MS tissue have indicated that the events involved in the immunopathogenesis of MS may be more complicated.

scholarly journals Role of Natalizumab in Relapsing-Remitting Multiple Sclerosis: A review

2021 ◽  
Vol 2 (1) ◽  
pp. 2-12
Author(s):  
Anuj Krishna Paudel ◽  
Sanjiv Bastakoti ◽  
Nitesh Raj Dulal ◽  
Gunja Piya ◽  
Sashi Bhusan Singh
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Side Effects ◽  
Literature Review ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Introduction: Multiple sclerosis is a non-traumatic neurological disease caused by an immune-mediated reaction leading to a chronic inflammatory demyelinating disorder of the central nervous system. The treatments for multiple sclerosis are mainly divided into three categories: treatment of exacerbation, slowing disease progression with disease-modifying therapies, and symptomatic therapies. Natalizumab is a monoclonal antibody that works by preventing the adhesion of lymphocytes into the endothelium of the blood-brain barrier, reducing lymphocyte infiltration into the central nervous system. This review aims to study the efficacy and safety of natalizumab in relapsing-remitting multiple sclerosis. Methods: The review was performed using databases like PubMed, Cochrane library, Google scholar from which 48 relevant articles were selected based on the various inclusion criteria. The following keywords were used: “Natalizumab”, “Multiple sclerosis”, “side effects”, “Relapsing-remitting multiple sclerosis”, “progressive multifocal leukoencephalopathy” in different combinations. Results: The literature review suggests that natalizumab reduces the rate of sustained progression of the disease and disability, and was associated with a lower relapse rate in patients with relapsing-remitting multiple sclerosis. However, Progressive multifocal leukoencephalopathy is one of the serious side effects of natalizumab. Conclusion: The literature review suggests that Natalizumab has favorable outcomes in patients with relapsing-remitting multiple sclerosis. Since progressive multifocal leukoencephalopathy is one of the serious side effects of natalizumab, risk stratification should be done.

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