Progress in the Application of Drugs for the Treatment of Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune and chronic inflammatory demyelinating disease of the central nervous system (CNS), which gives rise to focal lesion in CNS and cause physical disorders. Although environmental factors and susceptibility genes are reported to play a role in the pathogenesis of MS, its etiology still remains unclear. At present, there is no complete cure, but there are drugs that decelerate the progression of MS. Traditional therapies are disease-modifying drugs that control disease severity. MS drugs that are currently marketed mainly aim at the immune system; however, increasing attention is being paid to the development of new treatment strategies targeting the CNS. Further, the number of neuroprotective drugs is presently undergoing clinical trials and may prove useful for the improvement of neuronal function and survival. In this review, we have summarized the recent application of drugs used in MS treatment, mainly introducing new drugs with immunomodulatory, neuroprotective, or regenerative properties and their possible treatment strategies for MS. Additionally, we have presented Food and Drug Administration-approved MS treatment drugs and their administration methods, mechanisms of action, safety, and effectiveness, thereby evaluating their treatment efficacy.

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HIV infection and multiple sclerosis: a case with unexpected “no evidence of disease activity” status

Journal of International Medical Research ◽

10.1177/0300060521999577 ◽

2021 ◽

Vol 49 (3) ◽

pp. 030006052199957

Author(s):

Fernando Labella ◽

Fernando Acebrón ◽

María del Carmen Blanco-Valero ◽

Alba Rodrígez-Martín ◽

Ángela Monterde Ortega ◽

...

Keyword(s):

Multiple Sclerosis ◽

Hiv Infection ◽

Disease Activity ◽

Demyelinating Disease ◽

Clinical Course ◽

Disease Modifying Drugs ◽

Immunodeficiency Virus ◽

Relapsing Remitting ◽

The Central Nervous System ◽

Disease Modifying

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system whose etiology remains unclear. It has been suggested that MS can be triggered by certain viruses; however, human immunodeficiency virus (HIV) infection is associated with reduced incidence of MS. We present the case of a young patient diagnosed with active relapsing-remitting MS whose clinical course substantially improved following HIV infection and treatment. The patient achieved no evidence of disease activity status without any disease-modifying drugs. Both HIV-induced immunosuppression and antiretroviral therapy may have attenuated the clinical course in this patient.

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Fair data for next-generation management of multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458517748475 ◽

2017 ◽

Vol 24 (9) ◽

pp. 1151-1156 ◽

Cited By ~ 3

Author(s):

Liesbet M Peeters

Keyword(s):

Multiple Sclerosis ◽

Multidisciplinary Treatment ◽

Treatment Strategies ◽

Population Based ◽

Disease Modifying Drugs ◽

Disease Epidemiology ◽

Individual Level ◽

Precision Level ◽

The Central Nervous System ◽

The Individual

Multiple sclerosis (MS) is a progressive demyelinating and degenerative disease of the central nervous system with symptoms depending on the disease type and the site of lesions and is featured by heterogeneity of clinical expressions and responses to treatment strategies. An individualized clinical follow-up and multidisciplinary treatment is required. Transforming the population-based management of today into an individualized, personalized and precision-level management is a major goal in research. Indeed, a complex and unique interplay between genetic background and environmental exposure in each case likely determines clinical heterogeneity. To reach insights at the individual level, extensive amount of data are required. Many databases have been developed over the last few decades, but access to them is limited, and data are acquired in different ways and differences in definitions and indexing and software platforms preclude direct integration. Most existing (inter)national registers and IT platforms are strictly observational or focus on disease epidemiology or access to new disease modifying drugs. Here, a method to revolutionize management of MS to a personalized, individualized and precision level is outlined. The key to achieve this next level is FAIR data.

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The pattern of thyroiditis in multiple sclerosis: a cross-sectional study in a tertiary care hospital in Egypt

The Egyptian Journal of Internal Medicine ◽

10.1186/s43162-020-00017-w ◽

2020 ◽

Vol 32 (1) ◽

Author(s):

Nearmeen M. Rashad ◽

Marwa G. Amer ◽

Waleed M. Reda Ashour ◽

Hassan M. Hassanin

Keyword(s):

Multiple Sclerosis ◽

Interferon Beta ◽

Demyelinating Disease ◽

Tertiary Care ◽

Cross Sectional Study ◽

Care Hospital ◽

Sectional Study ◽

Cmv Infection ◽

Cross Sectional ◽

Disease Modifying Drugs

Abstract Background Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system with varied clinical features. Disease-modifying drugs (DMDs) of MS associated with different types of thyroiditis. In this cross-sectional study, we aimed to assess the prevalence of thyroid dysfunction in MS and to investigate the association between DMDs and the risk of thyroiditis in MS. A cross-sectional study included 100 patients with relapsing-remitting multiple sclerosis (RRMS) in relapse, and the diagnosed was according to revised McDonald’s criteria 2010. Results Our results revealed that the prevalence of thyroiditis was 40%; autoimmune (34%) and infective (6%) among patients with RRMS in relapse and cerebellar symptoms were significantly higher in patients with thyroiditis compared to patients without thyroiditis. Regarding the association between DMDs and thyroiditis, the prevalence of patients treated with interferon-beta-1b was higher in MS patients with thyroiditis compared to MS patients without thyroiditis. However, the prevalence of patients treated with interferon-beta-1a was lower in MS patients with thyroiditis compared to MS patients without thyroiditis. In addition, we found CMV infection was more common in patients treated by interferon beta-1b and candida infection was common in patients treated by fingolimod. Conclusions Thyroiditis is commonly observed in patients with RRMS in relapse and higher prevalence of patients treated with interferon-beta-1b which is commonly associated with thyroiditis and CMV infection; however, candida thyroid infection was common in MS patients treated by fingolimod.

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Risks and risk management in modern multiple sclerosis immunotherapeutic treatment

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756286419836571 ◽

2019 ◽

Vol 12 ◽

pp. 175628641983657 ◽

Cited By ~ 22

Author(s):

Luisa Klotz ◽

Joachim Havla ◽

Nicholas Schwab ◽

Reinhard Hohlfeld ◽

Michael Barnett ◽

...

Keyword(s):

Multiple Sclerosis ◽

Side Effect ◽

Paradigm Shift ◽

Mechanisms Of Action ◽

Optimal Choice ◽

New Drugs ◽

Comprehensive Overview ◽

Disease Modifying Drugs ◽

Practical Recommendations ◽

Target Effects

In recent years, there has been a paradigm shift in the treatment of multiple sclerosis (MS) owing to the approval of a number of new drugs with very distinct mechanisms of action. All approved disease-modifying drugs primarily work directly on the immune system. However, the identification of an ‘optimal choice’ for individual patients with regard to treatment efficacy, treatment adherence and side-effect profile has become increasingly complex including conceptual as well as practical considerations. Similarly, there are peculiarities and specific requirements with regard to treatment monitoring, especially in relation to immunosuppression, the development of secondary immune-related complications, as well as the existence of drug-specific on- and off-target effects. Both classical immunosuppression and selective immune interventions generate a spectrum of potential therapy-related complications. This article provides a comprehensive overview of available immunotherapeutics for MS and their risks, detailing individual mechanisms of action and side-effect profiles. Furthermore, practical recommendations for patients treated with modern MS immunotherapeutics are provided.

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Recent advances on immunosuppressive drugs and remyelination enhancers for the treatment of multiple sclerosis

Current Pharmaceutical Design ◽

10.2174/1381612827666210127121829 ◽

2021 ◽

Vol 27 ◽

Author(s):

Jennifer Cadenas-Fernández ◽

Pablo Ahumada-Pascual ◽

Luis Sanz Andreu ◽

Ana Velasco

Keyword(s):

Multiple Sclerosis ◽

Intracellular Signaling ◽

Demyelinating Disease ◽

Lipid Synthesis ◽

Immunosuppressive Drugs ◽

Nerve Fibers ◽

Myelin Sheaths ◽

Demyelinating Lesions ◽

The Central Nervous System ◽

Lipid Structures

: Mammalian nervous systems depend crucially on myelin sheaths covering the axons. In the central nervous system, myelin sheaths consist of lipid structures which are generated from the membrane of oligodendrocytes (OL). These sheaths allow fast nerve transmission, protect axons and provide them metabolic support. In response to specific traumas or pathologies, these lipid structures can be destabilized and generate demyelinating lesions. Multiple sclerosis (MS) is an example of a demyelinating disease in which the myelin sheaths surrounding the nerve fibers of the brain and spinal cord are damaged. MS is the leading cause of neurological disability in young adults in many countries, and its incidence has been increasing in recent decades. Related to its etiology, it is known that MS is an autoimmune and inflammatory CNS disease. However, there are no effective treatments for this disease and the immunomodulatory therapies that currently exist have proven limited success since they only delay the progress of the disease. Nowadays, one of the main goals in the MS research is to find treatments which allows the recovery of neurological disabilities due to demyelination. To this end, different approaches, such as modulating intracellular signaling or regulating the lipid metabolism of OLs, are being considered. Here, in addition to immunosuppressive or immunomodulatory drugs that reduce the immune response against myelin sheaths, we review a diverse group of drugs that promotes endogenous remyelination in MS patients and whose use may be interesting as potential therapeutic agents in MS disease. To this end, we compile specific treatments against MS that are currently in the market with remyelination strategies which have entered into human clinical trials for future reparative MS therapies. The method used in this study is a systematic literature review on PubMed, Web of Science and Science Direct databases up to May 31, 2020. To narrow down the search results in databases, more specific keywords, such as, “myelin sheath”, “remyelination”, “demyelination”, “oligodendrocyte” and “lipid synthesis” were used to focus the search. We favoured papers published after January, 2015, but did not exclude earlier seminal papers.

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Relapsing Tumefactive Demyelination: A Case Report

Acta Medica Academica ◽

10.5644/ama2006-124.231 ◽

2018 ◽

Vol 47 (2) ◽

pp. 193

Author(s):

Ibrahim Omerhodžić ◽

Almir Džurlić ◽

Dino Lisica ◽

Nevena Mahmutbegović ◽

Maida Nikšić ◽

...

Keyword(s):

Multiple Sclerosis ◽

Case Report ◽

Female Patient ◽

Demyelinating Disease ◽

Diagnostic Procedures ◽

Young Female ◽

Diagnostic Challenge ◽

Fresh Frozen ◽

The Central Nervous System ◽

Tumorlike Lesion

Objective. We present a case of relapsing tumefactive demyelination in a young female patient, that posed a real diagnostic challenge, with a heterogeneous clinical picture, atypical for multiple sclerosis (MS) presentation, and neuroradiological manifestations with a high suspicion of neoplastic diseases.Case Report. An 18-year old female patient presented to our Neurosurgical Out-patients’ Clinic with symptoms atypical for multiple sclerosis, unremarkable neurological deficit, one tumefactive lesion on MRI, followed by relapse and another two lesions within a period of six months. We decided to perform biopsy of the tumefactive lesion with compressive effect. Serological and clinical data were negative for MS, and the patient did not respond well to corticosteroid therapy. Fresh frozen tumor tissue aroused a strong suspicion of gemistocytic astrocytoma, so total resection was done, but the definitive pathohistological examination confirmed tumefactive demyelination.Conclusion. For clinicians, it is important to consider demyelinating disease in the differential diagnosis of a tumorlike lesion of the central nervous system, in order to avoid invasive and potentially harmful diagnostic procedures, especially in younger patients.

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ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458517751049 ◽

2018 ◽

Vol 24 (2) ◽

pp. 96-120 ◽

Cited By ~ 180

Author(s):

Xavier Montalban ◽

Ralf Gold ◽

Alan J Thompson ◽

Susana Otero-Romero ◽

Maria Pia Amato ◽

...

Keyword(s):

Multiple Sclerosis ◽

Pharmacological Treatment ◽

Complex Disease ◽

Treatment Decisions ◽

Current Data ◽

New Drugs ◽

Nominal Group ◽

Disease Modifying Drugs ◽

Quality Of Evidence

Background: Multiple sclerosis (MS) is a complex disease with new drugs becoming available in the past years. There is a need for a reference tool compiling current data to aid professionals in treatment decisions. Objectives: To develop an evidence-based clinical practice guideline for the pharmacological treatment of people with MS. Methods: This guideline has been developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and following the updated EAN recommendations. Clinical questions were formulated in Patients–Intervention–Comparator–Outcome (PICO) format and outcomes were prioritized. The quality of evidence was rated into four categories according to the risk of bias. The recommendations with assigned strength (strong and weak) were formulated based on the quality of evidence and the risk-benefit balance. Consensus between the panelists was reached by use of the modified nominal group technique. Results: A total of 10 questions were agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency (EMA) at the time of publication. A total of 21 recommendations were agreed by the guideline working group after three rounds of consensus. Conclusion: The present guideline will enable homogeneity of treatment decisions across Europe.

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Multiple Sclerosis

Neuropathic Pain ◽

10.1093/med/9780190298357.003.0024 ◽

2018 ◽

pp. 209-216

Author(s):

Samuel W. Samuel ◽

Jianguo Cheng

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Neuropathic Pain ◽

Demyelinating Disease ◽

Spontaneous Pain ◽

Disease Course ◽

The Central Nervous System ◽

Disease Modifying ◽

Multiple Treatments ◽

Surgical Treatments

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS). The diagnosis is based on evidence of at lease two different lesions in the CNS, at least two different episodes in the disease course, and chronic inflammation of the CNS as determined by analysis of the cerebrospinal fluid. Central neuropathic pain is the most common form of pain in patients with MS, with an estimated prevalence of about 50%. Along with the classical neuropathic pain features, such as spontaneous pain (dysesthesia and burning) and evoked pain (allodynia and hyperalgesia), patients with MS may also suffer from intermittent neuropathic pain, such as trigeminal neuralgia, Lhermitte sign, and glossopharyngeal neuralgia. In addition to disease-modifying therapies of MS, multiple treatments are available to manage neuropathic pain secondary to MS, including medical, interventional, and surgical treatments with varying levels of evidence.

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Exome-Sequence Analyses of Four Multi-Incident Multiple Sclerosis Families

Genes ◽

10.3390/genes11090988 ◽

2020 ◽

Vol 11 (9) ◽

pp. 988

Author(s):

Tobias Zrzavy ◽

Fritz Leutmezer ◽

Wolfgang Kristoferitsch ◽

Barbara Kornek ◽

Christine Schneider ◽

...

Keyword(s):

Multiple Sclerosis ◽

Genome Wide Association Study ◽

Rare Variants ◽

Demyelinating Disease ◽

Phenotypic Variability ◽

Convincing Evidence ◽

Risk Variants ◽

Unbiased Manner ◽

The Central Nervous System ◽

Reduced Penetrance

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the Central Nervous System (CNS). Currently, it is estimated that 30–40% of the phenotypic variability of MS can be explained by genetic factors. However, low susceptibility variants identified through Genome Wide Association Study (GWAS) were calculated to explain about 50% of the heritability. Whether familial high-risk variants also contribute to heritability is a subject of controversy. In the last few years, several familial variants have been nominated, but none of them have been unequivocally confirmed. One reason for this may be that genetic heterogeneity and reduced penetrance are hindering detection. Sequencing a large number of MS families is needed to answer this question. In this study, we performed whole exome sequencing in four multi-case families, of which at least three affected individuals per family were analyzed. We identified a total of 138 rare variants segregating with disease in each of the families. Although no single variant showed convincing evidence for disease causation, some genes seemed particularly interesting based on their biological function. The main aim of this study was to provide a complete list of all rare segregating variants to provide the possibility for other researchers to cross-check familial candidate genes in an unbiased manner.

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Association between disease-modifying therapies for multiple sclerosis and healthcare utilisation on a population level: a retrospective cohort study

BMJ Open ◽

10.1136/bmjopen-2019-033599 ◽

2019 ◽

Vol 9 (11) ◽

pp. e033599 ◽

Cited By ~ 2

Author(s):

Lina Al-Sakran ◽

Ruth Ann Marrie ◽

David Blackburn ◽

Katherine Knox ◽

Charity Evans

Keyword(s):

Multiple Sclerosis ◽

Retrospective Cohort ◽

Negative Binomial ◽

Demyelinating Disease ◽

Treatment Strategies ◽

Cost Benefit ◽

Healthcare Utilisation ◽

Population Level ◽

Disease Modifying ◽

The Impact

ObjectiveDisease-modifying therapy (DMT) use in multiple sclerosis (MS) has increased significantly. However, the impact of DMTs on healthcare use is limited and conflicting, and rarely examined at a population level. This study examined the association between DMTs and healthcare utilisation at the population level.DesignRetrospective cohort.SettingHealth administrative data from Saskatchewan, Canada (1997–2016).ParticipantsTo test for associations at the population level, we identified two cohorts. The general population cohort included all Saskatchewan residents ≥18 years who were drug plan beneficiaries. The MS cohort included individuals ≥18 years, identified using a validated definition (≥3 hospital, physician or drug claims for MS).Main outcome measures and methodsTo test for an association between the total number of DMT dispensations per year and the total number of hospitalisations we used negative binomial regression fitted with generalised estimating equations (GEE); only hospitalisations that occurred after the date of MS diagnosis (date of first claim for MS or demyelinating disease) were extracted. To test for an association between the number of DMT dispensations and physician claims, negative binomial distributions with GEE were fit as above. Results were reported as rate ratios (RR), with 95% CIs, and calculated for every 1000 DMT dispensations.ResultsThe number of DMT dispensations was associated with a decreased risk for all-cause (RR=0.994; 95% CI 0.992 to 0.996) and MS-specific (RR=0.909; 95% CI 0.880 to 0.938) hospitalisations. The number of DMT dispensations was not associated with the number of all-cause (RR=1.006; 95% CI 0.990 to 1.022) or MS-specific (RR=0.962; 95% CI 0.910 to 1.016) physician claims.ConclusionIncreased DMT use in Saskatchewan was associated with a reduction in hospitalisations, but did not impact the number of physician services used. Additional research on cost-benefit and differing treatment strategies would provide further insight into the true impact of DMTs on healthcare utilisation at a population level.

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