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Review Article | DOI: https://doi.org/10.31579/2578-8868/023
1 Department of Neuropsychology Iran
*Corresponding Author: Jenkins Johnson, Department of Neuropsychology Iran
Citation: Jenkins Johnson, Lakies Anil A Brief Review Chronic Inflammatory Autoimmune Disease: Multiple Sclerosis Pathogenesis and Treatment, DOI: 10.31579/2578-8868/023
Copyright: © 2017. Jenkins Johnson.This is an open-access article distributed under the terms of the
Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 15 October 2017 | Accepted: 16 November 2017 | Published: 15 December 2017
Keywords: nuerological degenerative diseases;tranumatic brain injury
Multiple sclerosis (MS) is a chronic inflammatory autoimmune demyelinating disease of the central nervous system. It affects approximately 400,000 people in the United States and onset is usually during young adulthood. There are four clinical forms of MS, of which relapsing remitting type is the most common. As the etiology of MS is unknown, finding a cure will remain challenging. The main mechanism of injury appears to be inflammation and 8 agents are now FDA approved to help control MS. These agents for relapsing forms of MS target different parts of the immune system, with the end goal of decreasing and avoiding further inflammation.
Multiple sclerosis (MS) is a chronic inflammatory autoimmune demyelinating disease of the central nervous system. Multiple sclerosis affects approximately 400,000 people in the United States alone, most of them being young adults. It expresses itself in four clinical forms: relapsing remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS), and progressive relapsing MD (PRMS) Approximately 87% of patients present with RRMS, characterized by acute attacks (relapses) followed by partial or full recovery (remission). Patients can manifest with a heterogeneous group of symptoms including changes in vision (unilateral visual loss, diplopia), weakness, dyscoordination, sensory loss or distortions, or changes in bowel and bladder function. Less diagnostic but also disabling symptoms include cognitive change, fatigue, and mood disturbance. Progression of disease may eventually lead to severe disability. Many medications and other measures may be used to ameliorate MS symptoms. The availability of disease modifying therapies has revolutionized the care of patients with the relapsing forms of this disease. These medications help control the underlying disease process, probably by decreasing immune mediated inflammation. They do not cure the disease or reverse the damage that has occurred with prior events. In general the effects of these agents appear more potent when they are given to patients before more severe widespread damage and disability have occurred. As the number of FDA-approved therapies continues to increase and other investigational and off label uses expands, it is helpful to review both the pathogenesis of MS and the effects of the pharmacologic agents.
PATHOGENESIS OF MULTIPLE SCLEROSIS
Inflammation of central nervous system is the primary cause of damage in MS. The specific elements that start this inflammation are still unknown. Studies have suggested that genetic, environmental and infectious agents may be among the factors influencing the development of MS. Many immunological studies have been done on the animal model for human MS known as the experimental autoimmune encephalomyelitis (EAE). Based on this model and observations of MS in humans, roles of several immunological pathways involved in MS are being explored. To understand these pathways it is important to first understand some basic points of the immune system in MS. While we have learned much about the immune system by the study of EAE, our lack of understanding of the differences between EAE and MS as well as the complexity of MS (and likely different immunologic subtypes of MS) must be kept in mind when reviewing experimental and immunologic data
TREATMENT OF MULTIPLE SCLEROSIS
There are currently 8 FDA approved agents for relapsing forms of MS. No agents are FDA approved for the primary progressive version of MS FDA approved agents include four preparations of interferon-beta (Avonex, Rebif, Betaseron and Extavia), glatiramer acetate (Copaxone), mitoxantrone (Novantrone), and natalizumab (Tysabri) and the recently approved first oral medication fingolimod (Gilenya) Many other immunologically active agents are used off label and others are nearing study completion and FDA application. The differing types and durations of immunologic effects of these agents will increase the complexity and likely risks of future MS care.
Beta Interferons (Avonex, Betaseron, Rebif, Extavia)
The four beta interferon drugs––Avonex (Biogen Idec), Rebif (Pfizer), Betaseron (Bayer), and Extavia (Novartis)––are naturally occurring cytokines secreted by immune cells. These agents inhibit viral replication via a variety of immunomodulating and antiviral activities.
Although the mechanisms of action of interferons beta-1a and beta-1b in MS are unknown, these cytokines perform regulatory functions in the immune system, and their anti-inflammatory properties are thought to be beneficial.The beta interferons have been shown to reduce the incidence of relapses by approximately one-third and are recommended for patients with relapsing–remitting MS who have intolerance to glatiramer acetate.In randomized, double-blind, placebo-controlled trials, the use of beta interferons in patients with MS reduced inflammatory lesions by 50% to 80%, as shown on brain MRI scans.Moreover, there is evidence that these drugs improve quality of life and cognitive function.
Glatiramer Acetate (Copaxone)
Glatiramer acetate (Copaxone, Teva) is a synthesized copolymer polypeptide mixture consisting of l-glutamic acid, l-lysine, l-alanine, and l-tyrosine. The drug was originally designed to mimic and compete with myelin basic protein.7 Subcutaneous (SQ) glatiramer acetate (20 mg/day) has been shown to reduce the rate of attacks in patients with relapsing–remitting MS.
Mitoxantrone (Novantrone)
Prior to its approval for use in MS, mitoxantrone (Novantrone, EMD Serono) was used to treat certain forms of cancer. Mitoxantrone suppresses the activity of T cells, B cells, and macrophages that are thought to lead the attack on the myelin sheath. As a synthetic antineoplastic anthracenedione, it intercalates into DNA and interferes with RNA. This medication is a potent inhibitor of topoisomerase II, an enzyme responsible for repairing damaged DNA.
Natalizumab (Tysabri)
Natalizumab (Tysabri, Biogen Idec/Elan) is a recombinant humanized immunoglobulin (IgG4) monoclonal antibody. Like the beta interferons and glatiramer acetate, its precise mechanism of action in patients with MS has not been fully defined. Natalizumab binds to the alpha 4-subunit of alpha 4β1 and alpha 4β7 integrins expressed on the surface of leukocytes (except neutrophils), and it inhibits the alpha 4–mediated adhesion of leukocytes to their counterreceptors.
Fingolimod (Gilenya)
Fingolimod (Gilenya, Novartis) is the first orally administered, disease-modifying drug approved by the FDA to reduce relapses and to delay the progression of disability in patients with relapsing forms of MS.Fingolimod is a sphingosine-1-phosphate receptor modulator that is metabolized by sphingosine kinase to the active metabolite fingolimod phosphate, which in turn blocks the migration of lymphocytes from lymph nodes, thereby reducing the number of lymphocytes in peripheral blood. The mechanism underlying the therapeutic effect of fingolimod in MS is unknown, but it might involve the reduction of lymphocyte migration into the CNS.
SYMPTOMATIC TREATMENT
Dalfampridine (Ampyra)
Dalfampridine (Ampyra, Acorda) is the first drug approved by the FDA that has been found to improve walking in patients with any type of MS.In clinical studies, approximately one-third of dalfampridine-treated patients had faster walking speeds compared with placebo-treated patients. The average walking speed was approximately 25