Frontiers in Clinical Drug Research - CNS and Neurological Disorders: Volume 9

Atta-ur-Rahman, Zareen Amtul

• Publisher: Bentham Science Publishers
• Year: 2021
• ISBN:
  9781681089041
• Topic: Physical Sciences
• Subtopic: Clinical Chemistry

Frontiers in Clinical Drug Research - CNS and Neurological Disorders is a book series that brings updated reviews to readers interested in advances in the development of pharmaceutical agents for the treatment of central nervous system (CNS) and other nerve disorders. The scope of the book series covers a range of topics including the medicinal chemistry, pharmacology, molecular biology and biochemistry of contemporary molecular targets involved in neurological and CNS disorders. Reviews presented in the series are mainly focused on clinical and therapeutic aspects of novel drugs intended for these targets. Frontiers in Clinical Drug Research - CNS and Neurological Disorders is a valuable resource for pharmaceutical scientists and postgraduate students seeking updated and critical information for developing clinical trials and devising research plans in the field of neurology. The ninth volume of this series features reviews that cover the following topics related to the treatment of a different CNS disorders, related diseases and basic neuropharmacology research: - Integrating imaging and microdialysis into systems neuropharmacology - Depression heterogeneity and the potential of a transdiagnostic and dimensional approach to identify biologically relevant phenotypes - CAR-T cells in brain tumors and autoimmune diseases – from basics to the clinic - Revaluation of thyrotropin-releasing hormone and its mimetics as candidates for treating a wide range of neurological and psychiatric disorders - Natural BACE1 inhibitors: promising drugs for the management of Alzheimer's disease - The possibilities of safe lithium therapy in the treatment of neurological and psychoemotional disorders - Pharmacotherapy of multiple sclerosis and treatment strategies

Pharmacotherapy of Multiple Sclerosis and Treatment Strategies

Amany Ragab^{1, *}, Ali Ibrahim², Rania Helal³, Ahmed Elsaid⁴, Hossam Younis⁵, Mona Elsherbiny⁶, Takwa Elkhatib⁷

¹ Cairo University, Cairo, Egypt

² Damascus Hospital, Damascus, Syria

³ Zagazig University, Zagazig, Egypt

⁴ Maadi military medical complex, Cairo, Egypt

⁵ Matarya teaching hospital, Cairo, Egypt

⁶ Police Hospital, Cairo, Egypt

⁷ Zagazig University, Zagazig, Egypt

Abstract

Multiple sclerosis (MS) is a well-known chronic inflammatory and neurodegenerative disease of the central nervous system (CNS). It is considered the most common autoimmune demyelinating disease of the CNS. It affects mainly young adult females between 20-40 years of age. MS was previously considered a T-lymphocyte-disease, but now B lymphocytes appeared to have a critical role in MS's pathogenesis. Affected patients showed lower quality of life with an increased death rate than the general population. The treatment of MS is challenging, and many drugs have evolved primarily for the last 20-30 years. Since the introduction of interferons in 1993, there are more than sixteen disease-modifying therapies (DMTs) approved. These drugs have different pharmacologic forms like injections, oral forms, and intravenous infusion drugs. Each one has its benefits and drawbacks. Moreover, like any other patient, MS patient has other symptoms that are not covered by DMT and need symptomatic treatment. In this chapter, we attempt to present medications used to treat acute relapse, different DMTs, symptomatic treatment for different MS symptoms. Besides, we give attention to drugs under clinical trials.

Keywords: Acute Relapse, Disease-modifying Therapy (DMT), Multiple Sclerosis (MS), Symptomatic Treatment.

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^* Corresponding author: Amany Hussein Ragab: Department of Neurology, Kasr-Alainy, Faculty of Medicine, Cairo University, Cairo, Egypt; Tel: [phone]; E-mail: [email protected]

INTRODUCTION

Multiple sclerosis (MS) is a well-known chronic inflammatory and neurode-

generative disease of the central nervous system (CNS). It is considered the most common autoimmune demyelinating disease of the CNS [1, 2]. MS affects mainly young adult females between 20-40 years of age [3]. The prevalence of MS varies with latitude, with an estimated global prevalence of 30.1 cases per 100,000 persons in 2016. The higher prevalence was found in North America, Western Europe, and Australia and lowest in eastern sub-Saharan Africa, central sub-Saharan Africa, and Oceania [4]. The precise etiology of the disease is not recognized. However, it is likely to develop in genetically susceptible individuals on exposure to various environmental factors [5]. MS is classified into four phenotypes: clinically isolated syndrome (CIS), relapsing-remitting (RR), primary progressive (PP), and secondary progressive (SP). Each type is further subcategorized to either active or non-active [6]. At disease presentation, 85% present with RRMS form, while 15% present with PPMS form. About 80% of patients with CIS who have typical brain lesions will develop MS during the follow-up. After 20 years, 80% of patients will develop SPMS [7]. RRMS presents with subacute onset of symptoms that may include optic neuritis, long-tract symptoms (weakness, numbness, paresthesias), impaired balance, brainstem dysfunction (internuclear ophthalmoplegia or nystagmus), transverse myelitis, or L'hermitte sign. PPMS present at a relatively older age (39-41 years), typically with a gradual progressive spastic paraparesis without sensory level [8, 9]. The pathogenesis of MS can be explained by self-reactive immune cells that break down the immune tolerance and reach the CNS, where they attack the myelin sheath. When reaching the CNS, these autoreactive lymphocytes start demyelination, axonal degeneration, synaptic loss, dying-back oligodendrogliopathy, tissue loss, and eventually astrogliosis [10, 11]. MS was previously considered a T-lymphocyte-disease, but now B lymphocytes have a critical role in MS's pathogenesis [12, 13]. The instant response to B-cell–depleting monoclonal antibodies suggests that antigen presentation and production of proinflammatory chemokines and cytokines by B lymphocytes (as contrasted to their antibody production role) may be more relevant to MS pathogenesis [14]. The discovery of the meningeal lymphoid follicle-like aggregates the possibility of intrathecal inflammation and may be responsible for disease progression [15]. Although the adaptive immune system drives the pathogenesis early in the disease, other mechanisms take the upper hand later. These disease processes are innate immune system, mitochondrial dysfunction, glutamate toxicity, and reduced compensatory ability. All these mechanisms l...