scholarly journals Monoclonal antibodies in the treatment of multiple sclerosis: from clinical research to practical application

2020 ◽  
pp. 88-94
Author(s):  
N. Yu. Lashch
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
Humanized Monoclonal Antibody ◽  
Complement Dependent Cytotoxicity ◽  
Dependent Cell ◽  
Magnetic Resonance Imaging Mri ◽  
Antibody Preparations ◽  
Brain And Spinal Cord ◽  
The Brain

Multiple sclerosis (MS) is a chronic autoimmune inflammatory demyelinating and neurodegenerative disease with a multifactorial etiology of development. MS in most cases has a wave-like course (periods of exacerbations and remissions), over time, the disease becomes progressive, which worsens the quality of life of patients. The drugs disease-modifying therapies (DMT) has been actively used in clinical practice for more than 30 years to prevent exacerbations and progression of MS. In patients with MS, in which the disease occurs with frequent exacerbations and signs of radiological activity of the demyelinating process, according to magnetic resonance imaging (MRI) of the brain and spinal cord, it is recommended to use monoclonal antibody preparations. The only drug registered for the treatment of primary progressive MS is ocrelizumab. In addition, ocrelizumab is indicated for patients with remitting and secondary progressive MS. Ocrelizumab is a humanized monoclonal antibody that selectively depletes a population of CD20+ B cells. The article presents data from clinical studies of OPERA I and OPERA II and describes a clinical case from the practice of a neurologist. Depletion of the B cell population is achieved by several mechanisms, including antibody-dependent cell-mediated phagocytosis, antibody-dependent T cell-mediated cytotoxicity, complement-dependent cytotoxicity, and apoptosis induction. The issues of efficacy and safety of ocrelizumab therapy in patients with MS are considered.

scholarly journals Use of monoclonal antibodies in patients with multiple sclerosis in the practice of a neurologist

2020 ◽  
pp. 69-75
Author(s):  
N. Yu. Lashch
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibodies ◽  
First Line ◽  
System Reconstruction ◽  
Progression Of Disease ◽  
Magnetic Resonance Imaging Mri ◽  
Antibody Preparations ◽  
Brain And Spinal Cord ◽  
The Brain

Multiple sclerosis (MS) ranks first for prevalence among diseases affecting the CNS white matter with 2.5 million cases estimated globally. InRussia, the number of cases is about 200 thousand. MS in most cases has a wavy course (periods of exacerbations and remissions), over time the progression of disease worses the quality of life of patients. The “gold standard” at the beginning of MS is first-line drugs disease-modifying therapies (DMT). If they are ineffective, it is necessary to strengthen the effect on the immune processes and the patient is prescribed second-line drugs (escalation of therapy). There is a method of induction therapy, when high activity of MS is recommended to start with drugs that have a strong immunosuppressive effect with a possible subsequent transition to soft supportive treatment. In patients with frequent exacerbations and signs of radiological activity of the disease, according to magnetic resonance imaging (MRI) of the brain and spinal cord, monoclonal antibody preparations are effectively used. Except of escalation and induction, it is also used the method of immune system reconstruction, which leads to a decrease in autoagression in MS. This article discusses a clinical case of using a drug of monoclonal antibodies that selectively bind to CD 52 on the surface of lymphocytes. The issues of efficacy and safety of alemtuzumab therapy in patients with MS are considered.

Depression and Inflammatory Markers in Veterans With Multiple Sclerosis

2021 ◽  
pp. 109980042110500
Author(s):  
Pamela Newland ◽  
Yelyzaveta Basan ◽  
Ling Chen ◽  
Gregory Wu
Keyword(s):  
Multiple Sclerosis ◽  
Inflammatory Markers ◽  
Pearson Correlation ◽  
Correlation Coefficients ◽  
The United States ◽  
Biological Mechanisms ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
The Brain

Multiple sclerosis (MS), an inflammatory neurodegenerative disease of the central nervous system (CNS), afflicts over one per thousand people in the United States. The pathology of MS typically involves lesions in several regions, including the brain and spinal cord. The manifestation of MS is variable and carries great potential to negatively impact quality of life (QOL). Evidence that inflammatory markers are related to depression in MS is accumulating. However, there are barriers in precisely identifying the biological mechanisms underlying depression and inflammation. Analysis of cytokines provides one promising approach for understanding the mechanisms that may contribute to MS symptoms. Methods: In this pilot study, we measured salivary levels of interleukin (IL)-6, IL-1beta (β), and IL-10 in 24 veterans with MS. Descriptive statistics were reported and Pearson correlation coefficients were obtained between cytokines and depression. Results: The anti-inflammatory cytokine IL-10 was significantly negatively associated with depression in veterans with MS (r = −0.47, p = .024). Conclusion: Cytokines may be useful for elucidating biological mechanisms associated with the depression and a measure for nurses caring for veterans with MS.

scholarly journals “No evident disease activity”: The use of combined assessments in the management of patients with multiple sclerosis

2017 ◽  
Vol 23 (9) ◽  
pp. 1179-1187 ◽  
Author(s):  
Gavin Giovannoni ◽  
Davorka Tomic ◽  
Jeremy R Bright ◽  
Eva Havrdová
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Brain Magnetic Resonance Imaging ◽  
Individual Patient Level ◽  
Patient Reported ◽  
Magnetic Resonance Imaging Mri ◽  
The Individual ◽  
The Brain

Using combined endpoints to define no evident disease activity (NEDA) is becoming increasingly common when setting targets for treatment outcomes in multiple sclerosis (MS). Historically, NEDA has taken account of the occurrence of relapses, brain magnetic resonance imaging (MRI) lesions and disability worsening, but this approach places emphasis on inflammatory activity in the brain and mostly overlooks ongoing neurodegenerative damage. Combined assessments of NEDA which take account of changes in brain volume or neuropsychological outcomes such as cognitive function may begin to address this imbalance, and such assessments may also consider blood or spinal-fluid neurofilament levels or patient-reported outcomes and quality of life measures. If a combined NEDA assessment can be validated in prospective studies as indicative of long-term disease remission at the individual patient level, treating to achieve NEDA could become the goal of clinical practice and achieving NEDA may become the “new normal” state of disease control for patients with MS.

scholarly journals MRI in the assessment and monitoring of multiple sclerosis: an update on best practice

2017 ◽  
Vol 10 (6) ◽  
pp. 247-261 ◽  
Author(s):  
Ulrike W. Kaunzner ◽  
Susan A. Gauthier
Keyword(s):  
Multiple Sclerosis ◽  
Best Practice ◽  
High Sensitivity ◽  
The Past ◽  
Assessment And Monitoring ◽  
Magnetic Resonance Imaging Mri ◽  
Improved Technology ◽  
Brain And Spinal Cord ◽  
The Brain

Magnetic resonance imaging (MRI) has developed into the most important tool for the diagnosis and monitoring of multiple sclerosis (MS). Its high sensitivity for the evaluation of inflammatory and neurodegenerative processes in the brain and spinal cord has made it the most commonly used technique for the evaluation of patients with MS. Moreover, MRI has become a powerful tool for treatment monitoring, safety assessment as well as for the prognostication of disease progression. Clinically, the use of MRI has increased in the past couple decades as a result of improved technology and increased availability that now extends well beyond academic centers. Consequently, there are numerous studies supporting the role of MRI in the management of patients with MS. The aim of this review is to summarize the latest insights into the utility of MRI in MS.

scholarly journals Efficacy and Safety of Existing and Emerging Monoclonal Antibody Therapies for Multiple Sclerosis

2016 ◽  
Vol 11 (2) ◽  
pp. 96
Author(s):  
Gavin Giovannoni ◽  
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Structural Characteristics ◽  
Single Class ◽  
Course Of Disease ◽  
Complement Dependent Cytotoxicity ◽  
Dependent Cell ◽  
Advanced Development ◽  
Target Effects

The introduction of monoclonal antibodies for multiple sclerosis (MS) has provided a molecular targeted approach to modify the course of disease. A major advantage of monoclonal antibodies in the treatment of MS is that they are designed to be specific to their target and have very few off-target effects. Monoclonal antibodies have distinct structural characteristics and different targets, and their various mechanisms of action include cross-linking, blocking interactions, induction of signal transduction via receptor binding, complement-dependent cytotoxicity, and antibody-dependent cell-mediated cytotoxicity. Monoclonal antibodies should not therefore be considered a single class of treatments. Natalizumab and alemtuzumab are highly efficacious treatments approved for treating MS, though they tend to be reserved for patients with more active disease. Other monoclonal antibodies in advanced development include ocrelizumab, ofatumumab, anti-CD25 monoclonal antibody, daclizumab and opicinumab (anti-LINGO-1). Screening and monitoring is required to enable the optimal utilisation of all monoclonal antibodies and the benefit–risk profile of each monoclonal antibody needs to be fully considered before use. At present, patients have variable access to effective MS treatments, and this issue is likely to become even more important to address as new therapies become available.

At the heart of primary progressive multiple sclerosis: three cases with diffuse MRI abnormalities only

2008 ◽  
Vol 14 (3) ◽  
pp. 428-430 ◽  
Author(s):  
JNP Zwemmer ◽  
JCJ Bot ◽  
B. Jelles ◽  
F. Barkhof ◽  
CH Polman
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Course ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Resonance Imaging ◽  
Focal Lesions ◽  
Primary Progressive ◽  
Magnetic Resonance Imaging Mri ◽  
Brain And Spinal Cord ◽  
Made In

We present three patients with a clinical course and cerebrospinal fluid findings consistent with a diagnosis of primary progressive multiple sclerosis (PPMS). Extensive and repeated magnetic resonance imaging (MRI) examinations showed only diffuse abnormality in brain and spinal cord, but no focal lesions. We propose that these cases represent the most pure form of PPMS, even though according to currently applied criteria this diagnosis can not be made in the absence of focal lesions on MRI. Multiple Sclerosis 2008; 14: 428—430. http://msj.sagepub.com

scholarly journals Brain and Spinal Cord MRI in Multiple Sclerosis: an Update

2017 ◽  
Vol 01 (04) ◽  
pp. E294-E306 ◽  
Author(s):  
Mike Wattjes ◽  
Peter Raab
Keyword(s):  
Multiple Sclerosis ◽  
Quantitative Mri ◽  
Central Vein ◽  
Resonance Imaging ◽  
Ultra High Field ◽  
Important Differential Diagnosis ◽  
Magnetic Resonance Imaging Mri ◽  
Near Future ◽  
Brain And Spinal Cord

AbstractMagnetic resonance imaging (MRI) plays an important role in the diagnosis of multiple sclerosis and has been incorporated into the McDonald diagnostic criteria for MS. In particular, for the exclusion of important differential diagnosis and comorbidities, new MRI markers have been established such as the “central vein sign”. In addition to diagnostic purposes, the role of MRI in MS monitoring is becoming increasingly important, particularly for pharmacovigilance. This includes treatment efficacy monitoring, prediction of treatment response and safety monitoring. Quantitative MRI methods and ultra-high-field MRI offer the opportunity for the quantitative assessment of damage in normal-appearing brain tissue. However, the standardization of these techniques with the goal of implementation in clinical routine will be one of the major challenges in the near future.

A phase II trial of anti-CD4 antibodies in the treatment of multiple sclerosis

1996 ◽  
Vol 1 (6) ◽  
pp. 339-342 ◽  
Author(s):  
BW vanOosten ◽  
M Lai ◽  
F Barkhof ◽  
DH Miller ◽  
IF Moseley ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Statistical Power ◽  
Primary Outcome Measure ◽  
T Helper ◽  
Effector Cells ◽  
Natural History Studies ◽  
Mri Scans ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain ◽  
Experimental Allergic

In multiple sclerosis (MS) myelin damage is the result of a chronic inflammatory process mediated by CD4 positive T helper/effector cells. In experimental allergic encephalomyelitis (EAE), the animal model of MS, treatment with anti-CD4 antibodies can prevent the onset of disease. Natural history studies have demonstrated that gadolinium enhanced magnetic resonance imaging (MRI) of the brain is more sensitive and objective in assessing inflammatory disease activity in MS than clinical monitoring, so that less patients and shorter studies suffice to reach the same statistical power as compared to trials using clinical outcome parameters. In this paper we describe the design of an exploratory trial of chimeric monoclonal anti-CD4 antibodies in the treatment of MS. For this study we chose the number of active MS lesions on monthly gadolinium enhanced MRI scans as the primary outcome measure.

Imaging

2017 ◽  
Author(s):  
Robert Laureno
Keyword(s):  
Resonance Imaging ◽  
Cross Sectional ◽  
Advantages And Disadvantages ◽  
Mri Scans ◽  
Cross Sectional Imaging ◽  
Magnetic Resonance Imaging Mri ◽  
Cellular Pathology ◽  
Brain And Spinal Cord ◽  
The Brain

This chapter on “Imaging” examines the relative advantages and disadvantages of computed tomography (CT) and magnetic resonance imaging (MRI) scans. It compares the modalities to each other and to gross neuropathology. For several decades, neurologists have been able to view cross-sectional images of living patients. Analogous to gross neuropathology, cross-sectional imaging displays the brain as an entire organ but does not demonstrate microscopic tissue or cellular pathology. By allowing practitioners to view sections of brain and spinal cord in vivo, imaging has improved neurologic practice and facilitated clinical research. This chapter deals with imaging topics that are important to the neurologist. The timing of scans, the effects of gravity, and the importance of plane of section are considered. Imaging is compared to gross neuropathology, and MRI is compared to CT.

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