Multiple Sclerosis and Neuroinflammation: The Overview of Current and Prospective Therapies.
Bjelobaba Ivana,Savic Danijela,Lavrnja Irena
Current pharmaceutical design
Persistent neuroinflammation is now recognized as a chief pathological component of practically all neurodegenerative diseases. Neuroinflammation in the central nervous system (CNS), is accompanied with immune responses of glial cells. Glial cells respond to pathological stimuli through antigen presentation, and cytokine and chemokine signaling. Therefore, limiting CNS inflammation represents prospective therapeutic approach in diseases like Alzheimer's, amyotrophic lateral sclerosis, Parkinson's, ischemia, various psychiatric disorders and Multiple sclerosis (MS). As a complex disease, MS is characterized by neuroinflamation, demyelination and sequential axonal loss. Due to unknown etiology and the heterogeneous presentation of the disease, MS is hard to treat and the search for potential therapeutics is wide and meticulous. However, finding a proper antineuroinflammatory drug may bring an advance in selecting novel treatment regimens of ample of neurodegenerative diseases and neurological disorders. The present review gives the overview of the existing and potential therapies in MS, aimed to modulate neuroinflammation and ensure neuroprotection.
10.2174/1381612822666161214153108
The Impact of Aging on Multiple Sclerosis.
Current neurology and neuroscience reports
PURPOSE OF REVIEW:Multiple sclerosis (MS) is a chronic, immune-mediated demyelinating disorder of the central nervous system. Age is one of the most important factors in determining MS phenotype. This review provides an overview of how age influences MS clinical characteristics, pathology, and treatment. RECENT FINDINGS:New methods for measuring aging have improved our understanding of the aging process in MS. New studies have characterized the molecular and cellular composition of chronic active or smoldering plaques in MS. These lesions are important contributors to disability progression in MS. These studies highlight the important role of immunosenescence and the innate immune system in sustaining chronic inflammation. Given these changes in immune function, several studies have assessed optimal treatment strategies in aging individuals with MS. MS phenotype is intimately linked with chronologic age and immunosenescence. While there are many unanswered questions, there has been much progress in understanding this relationship which may lead to more effective treatments for progressive disease.
10.1007/s11910-024-01333-2
An overview on disease modifying and symptomatic drug treatments for multiple sclerosis.
Expert review of clinical pharmacology
INTRODUCTION:Multiple sclerosis (MS) is an inflammatory and degenerative autoimmune condition, resulting frequently in a disabling condition. Significant improvements of long-term prognosis have been recently achieved with an early and more aggressive use of disease modifying therapies (DMTs). Addressing the complexity of managing its progressive forms remains a significant challenge. AREAS COVERED:This review provides an update on DMTs for relapsing-remitting MS (RRMS) and progressive MS and their efficacy, safety, and mechanism of action, emphasizing the critical role of biomarkers in optimizing treatment decisions. Moreover, some key information on drugs used to manage symptoms such as pain, fatigue, spasticity and urinary problems will be provided. The literature search was conducted using PubMed, Embase, and Cochrane Library databases covering the period from January 2000 to January 2024. EXPERT OPINION:Major advances have been achieved in the treatment of RRMS. Treatment should start immediately as soon as the neurologist is confident with the diagnosis and its choice should be based on the prognostic profile and on the patient's propensity to accept drug-related risks. The therapeutic landscape for progressive MS is quite disappointing and necessitates further innovation. Personalized medicine, leveraging biomarker insights, holds promise for refining treatment efficacy and patient outcomes.
10.1080/17512433.2024.2410393
Overview of the Current Pathophysiology of Fatigue in Multiple Sclerosis, Its Diagnosis and Treatment Options - Review Article.
Neuropsychiatric disease and treatment
Fatigue is a common, debilitating and often underestimated symptom in patients with multiple sclerosis (MS). The exact pathophysiological mechanism of fatigue in MS is still unknown. However, there are many theories involving different immunological, metabolic and inflammatory mechanisms of fatigue. Owing to the subjective nature of this symptom, its diagnosis is still very limited and is still based only on diagnostic questionnaires. Although several therapeutic agents have been used in the past to try to influence fatigue in MS patients, no single effective approach for the treatment of fatigue has yet been found. This review article aims to provide the reader with information on the current theories on the origin and mechanism of fatigue in MS, as well as diagnostic procedures and, finally, current therapeutic strategies for the management of fatigue in MS patients.
10.2147/NDT.S429862
Current and emerging treatment of multiple sclerosis.
Hart Felecia M,Bainbridge Jacquelyn
The American journal of managed care
The treatment of multiple sclerosis (MS) falls into 3 categories: treatment of exacerbations, slowing disease progression with disease-modifying therapies (DMTs), and symptomatic therapies. The management of MS is becoming increasingly complex with the development of additional DMTs that, like the older DMTs, reduce the frequency and severity of relapses, and the accumulation of lesions detected by magnetic resonance imaging. Initiating treatment to slow or reverse inflammatory lesion formation early in the course of the disease is advocated as a way to prevent accumulation of disability. Nevertheless, there is a lack of comparative efficacy data and few clinical guidelines to aid healthcare providers in the optimal selection of DMTs. Given that some of the newer agents are associated with potentially serious, but rare, adverse events, careful consideration of the risk-benefit profile is necessary to minimize the risk to patients. This article provides an overview of the existing treatments for MS with an emphasis on DMTs and emerging therapies.
The role of glial cells in multiple sclerosis disease progression.
Nature reviews. Neurology
Despite the development of highly effective treatments for relapsing-remitting multiple sclerosis (MS), limited progress has been made in addressing primary progressive or secondary progressive MS, both of which lead to loss of oligodendrocytes and neurons and axons, and to irreversible accumulation of disability. Neuroinflammation is central to all forms of MS. The current effective therapies for relapsing-remitting MS target the peripheral immune system; these treatments, however, have repeatedly failed in progressive MS. Greater understanding of inflammation driven by CNS-resident cells - including astrocytes and microglia - is, therefore, required to identify novel potential therapeutic opportunities. Advances in imaging, biomarker analysis and genomics suggest that microglia and astrocytes have central roles in the progressive disease process. In this Review, we provide an overview of the involvement of astrocytes and microglia at major sites of pathology in progressive MS. We discuss current and future therapeutic approaches to directly target glial cells, either to inhibit pathogenic functions or to restore homeostatic functions lost during the course of the disease. We also discuss how bidirectional communication between astrocytes and microglia needs to be considered, as therapeutic targeting of one is likely to alter the functions of the other.
10.1038/s41582-022-00624-x
Therapeutic Advances in Multiple Sclerosis.
Frontiers in neurology
Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system that causes significant disability and healthcare burden. The treatment of MS has evolved over the past three decades with development of new, high efficacy disease modifying therapies targeting various mechanisms including immune modulation, immune cell suppression or depletion and enhanced immune cell sequestration. Emerging therapies include CNS-penetrant Bruton's tyrosine kinase inhibitors and autologous hematopoietic stem cell transplantation as well as therapies aimed at remyelination or neuroprotection. Therapy development for progressive MS has been more challenging with limited efficacy of current approved agents for inactive disease and older patients with MS. The aim of this review is to provide a broad overview of the current therapeutic landscape for MS.
10.3389/fneur.2022.824926
The History of Diagnosis and Treatment of MS: a Brief Overview.
Current neurology and neuroscience reports
PURPOSE OF REVIEW:This overview of the history of diagnosis and treatment of multiple sclerosis serves as an introduction to the rich history of multiple sclerosis, and shows we are on a continuum of incremental advances that date back centuries. RECENT FINDINGS:The current understanding of MS demonstrates a dramatic series of advances and this brief historical overview will provide some context for these discoveries. Although cases we would now recognize as multiple sclerosis can be found in older literature and diaries, the contribution of Jean-Martin Charcot at the Salpêtrière in Paris in 1868 was to frame the clinical and pathological features of a disorder he called la sclérose en plaque disséminées. Soon after, reports came from many countries. Over the next half-century, the diagnosis was a clinical conclusion with no confirmatory tests. Some CSF and evoked potential tests later helped but it remained for the MRI imaging and oligoclonal banding to substantially aid the clinical diagnosis. It is tempting to think that therapy is new in MS, but in previous centuries, hundreds of drugs, procedures, and surgeries were applied to patients with MS, many more than we use today. It remained for the development of the randomized clinical trial to show which therapies were beneficial and safe. Everything changed in 1993 when the first of a long list of new therapies was approved, therapies that were shown to alter the activity and outcome of the disease.
10.1007/s11910-022-01217-3
Multiple sclerosis: Diagnosis, disease-modifying therapy and prognosis.
Australian journal of general practice
BACKGROUND:Multiple sclerosis (MS) is a multifocal inflammatory central nervous system disorder. There are now many highly effective disease-modifying therapies (DMTs) available as treatment options, which have a significant impact on disease activity and long-term disability. OBJECTIVE:The aim of this article is to provide a concise overview of the diagnosis, DMTs and prognosis of MS. DISCUSSION:The diagnosis of MS is made on clinicoradiological grounds to prove dissemination of disease in both time and space in the nervous system. While the expanding options of DMTs have had a significant impact on disability, they make medication selection for individual patients more complicated. Patients with MS often have a model of care shared between the neurologist and the general practitioner. This review article summarises the key aspects of the diagnosis, DMTs and prognosis of MS relevant to the general practitioner.
10.31128/AJGP-07-21-6103
Epidemiology and Pathophysiology of Multiple Sclerosis.
Continuum (Minneapolis, Minn.)
PURPOSE OF REVIEW:This article provides an overview of genetic, environmental, and lifestyle risk factors affecting the disease course of multiple sclerosis (MS) and reviews the pathophysiologic characteristics of both relapsing and progressive MS. RECENT FINDINGS:The prevalence of MS has increased in recent decades, and costs of care for patients with MS have risen dramatically. Black, Asian, and Hispanic individuals may be at risk for more severe MS-related disability. Multiple genetic MS risk factors have been identified. Factors such as low vitamin D levels and a history of Epstein-Barr virus, smoking, and obesity, especially during childhood, also influence MS risk. Traditionally thought to be a T-cell-mediated disease, recent research has highlighted the additional roles of B cells and microglia in both relapsing and progressive MS. SUMMARY:Complex interactions between genetic, environmental, and lifestyle factors affect the risk for MS as well as the disease course. People of color have historically been underrepresented in both MS clinical trials and literature, but current research is attempting to better clarify unique considerations in these groups. MS pathology consists of the focal inflammatory lesions that have been well characterized in relapsing MS, as well as a more widespread neurodegenerative component that is posited to drive progressive disease. Recent advances in characterization of both the inflammatory and neurodegenerative aspects of MS pathophysiology have yielded potential targets for future therapeutic options.
10.1212/CON.0000000000001136