Development of New Drugs for Multiple Sclerosis Therapy in Patients With Walking Disability

Abstract

Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system. The condition leads to demyelination and axonal damage. In the long run, it results in subsequent dysfunction of neurological systems. Disability is the most common symptom associated with MS. The development of new drugs for the treatment of this disease among patients with walking disability is an area that is not fully explored. The current study embarked on a systematic literature review to analyse existing and new drugs used to treat MS patients with walking disabilities. The findings reveal that the existence of recent therapies can help to delay and disrupt debilitation. Ocrelizumab is one of the successful drugs recently developed to manage walking disabilities among patients suffering from MS. The regimen is approved for use after undergoing phase III clinical trials and assessment with expandable disability status scale. Other drugs, such as Peg-interferon beta-1a and Daclizumab, are also approved to treat MS patients with various disabilities.

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Key words: multiple sclerosis, therapy, drugs

Development of New Drugs for Multiple Sclerosis Therapy in Patients with Walking Disability: A Systematic Literature Review

Introduction

Overview

Multiple sclerosis (herein referred to as MS) is an autoimmune disease affecting the central nervous system. The condition leads to demyelination and axonal damage. In the long run, MS results in subsequent dysfunction of neurological systems. A bigger proportion of MS patients tend to develop what Piehl (2014) refers to as neurological disability. In fact, MS is one of the most common causes of neurological disability. Until recently, treatment for this complication relied on disease-modifying agents. However, the management of the condition has reached a point where there is an increasing launch of new drugs in the market.

MS is a complex disease, and this has been linked to its molecular mechanism. For example, mitochondria, which is regarded as the powerhouse of cell has been linked to pathogenesis of MS. As more information about autoimmune has been acquire, especially with the molecular mechanism involved, several MS treatments have been developed.

During the initial course of MS, research illustrates that patients are more often than not affected by gait impairment. The disorder leads to various symptoms that include, among others, muscle weaknesses, body imbalance, coordination disorders, and spasticity problems. Research shows that half of the patients suffering from MS experience gait impairment. The manifestation entails reduced walking speed and distance. According to Lecat, Decavel, Magnin, Lucas, Gremeaux, and Sagawa (2017), gait impairment is the most debilitating symptom among patients suffering from MS. It accounts for at least 70% of the handled cases.

Walking is a fundamental aspect of daily activities. As such, any impairment in mobility will substantially reduce one's quality of life. The compromised ability to walk will subsequently result in not only social but also economic challenges. It is against this backdrop of MS and its associated risks of impaired mobility that the current paper is written. The paper aims to systematically review the development of new drugs for MS therapy among patients with walking disability.

Aims and Objectives of the Review

The current study reviews literature available on the new drugs used to manage gait impairment as a way of treating MS patients with walking disabilities. The objective of the study is to generate evidence-based results aimed at minimizing walking disabilities among patients with MS. To this end, the review will include drugs launched within the last three years for therapy of MS patients with walking problems.

Background Information

In the 1900s, there were only a few cases of MS in the medical field. However, the condition has become a common occurrence in neurological treatment. Today, over 2.5 million people are suffering from the affliction. The prevalence of MS has increased where 30 people in every 100,000 were diagnosed with the condition in 2008. The figure rose to 33 in every 100, 000 in 2014 (Piehl, 2014).

As aforementioned, MS is a chronic disorder that affects the central nervous system. The cause is unknown. However, most medical experts agree that the causes encompass genetic susceptibility and environmental exposure. Since there is no known treatment, most intervention measures for MS involve delaying the progression of the disease. The major objective of such a move is to improve the patient's quality of life. Another goal of this undertaking is to delay the onset of MS symptoms (Sagawa, Magnin, Paillot, Moulin, & Decavel, 2016).

There are four categories of MS condition. The disorders are defined based on their clinical course and increasing severity. Relapsing/remitting MS (RRMS) is the first category. It is the most common type of MS. According to Sagawa et al. (2016), RRMS affects over 85% of all MS patients. The second category is the secondary progressive MS (SPMS). It develops into RRMS after a short duration of time. The SPMS affects 8 to 10% of MS patients. It is a gradual and continuous neurologic deterioration. Progressive relapsing MS (PRMS) is the fourth category and the least common. It affects less than 5% of all MS patients (Sagawa et al., 2016). The PRMS is similar to PPMS except that it is characterized by overlapping relapses. All these conditions result in multiple sclerosis. Although there are treatments to minimize the rate of relapse in RRMS, the long-term impacts of these interventions are scarce. Also, there are limited medical therapies for the treatment of the progressive forms of MS. To this end, there is need to understand the development of new drugs for MS therapy among patients with walking disabilities.

There are many symptoms associated with MS. They include motor and cognitive impairment, pain, urinary dysfunction, and optic neuritis. However, walking disability is the most prevalent symptom (Piehl, 2014). In fact, this impairment is traditionally one of the symptoms used as a criterion to assess the progression of MS disorder. For example, Kurtzke (1983), as cited in Sagawa et al. (2016), used walking disability to determine the expanded disability status scale. Studies have consistently demonstrated that 70% to 75% of patients with MS exhibit walking disturbances, something that is noted even among those with mild expandable disability status scale. Walking is a practice that is utilized in almost all daily activities. As such, it is critical to the social participation and independence of persons. Studies suggest that treatment that addresses the walking problems will go a long way in reducing the burden shouldered by individuals with MS.

Introduction

The current study employed a systematic review research design. The methodology is a kind of literature review that employs methodical approaches to acquire data. It involves a critical appraisal and synthesize of studies conducted in a particular field of interest. The researcher formulates a strategy that synthesizes studies that relate to the research question. According to Bearman and Dawson (2013), systematic review of literature provides an exhaustive summary of the current evidence regarding the aim of the study. In the current paper, the author analyzes publications on the development of new drugs for MS therapy among patients with walking disability. The author employed five steps in the systematic review process. They include the assessment of articles to be included in the study, identification, selection, eligibility for inclusion, and adoption of articles. During the review, the method highlighted below was followed to ensure that no weaknesses affected the research process.

Assessment and Inclusion

To select articles for the current study, the author employed the criteria illustrated in Figure 1. All resources used by the researcher were validated based on this principle.

Identification of the Articles for Literature Review

To identify the required articles, the researcher typed key words and search terms into various databases. The major archive was PubMed. The phrases used include "multiple sclerosis," New therapies for "multiple sclerosis," New Drugs for "multiple sclerosis," and "multiple sclerosis" treatment for people with walking disabilities.

Selection of Articles

In this phase, the author carefully selected the resources to avoid duplication. Replication was avoided on the basis of the titles of the articles.

Eligibility for Inclusion

The researcher selected and included articles on the development of new drugs for MS therapy among patients with walking disability. If the abstracts did not mention at least some of these phrases, the articles were excluded from the review process. Also, publications that did not correspond to drugs developed within the last three years or which are not under research were not selected for the study.

The researcher separated the articles that met the inclusion criteria into two clusters. The categories were made up of those resources addressing new drugs on walking disabilities among MS patients and the ones reviewing new drugs that are three years old or those that have passed the third phase of approval. The summary for the selection and inclusion criteria is illustrated in Figure 2 below:

Results and Findings

Eriksson, Komen, Piehl, Malmstrom, Wettermark, and Euler (2018) conducted a study to describe how patients suffering from MS are utilizing disease-modifying treatments. The research was carried out among RRMS patients where the researchers assessed the impacts of the introduction of new drugs. Eriksson et al. (2018) analyzed MS therapeutic treatment between 2011 and 2017. The scholars observed an increase in the use of new drugs introduced within the last three years. The medications include teriflunomide, which was launched in June 2014, peginterferon beta-1a (introduced in 2015), and daclizumab, which is traced back to February 2017.

HavrdovaDepartment of Neurology and Center for Clinical Neuroscience, Charles University, Czech Republic, ArnoldDepartment of Neurology and Neurosurgery, McGill University, CanadaNeuroRx Research, Canada, Bar-OrDepartment of Neurology and Center for Neuroinflammation and Experimental Therapeutics, University of Pennsylvania, USA, ComiNeurology Department and INSPE-Institute of Experimental Neurology, Vita-Salute San Raffaele University, Italy, HartungMedical Faculty, Heinrich Heine University Dusseldorf, Germany, and Kappos (2018) carr...