Translational medicine is beginning to be successfully applied in multiple sclerosis (MS). This chapter reviews how advances in our understanding of MS and our ability to measure MS are contributing to the application of translational medicine in this disorder. It presents a historical perspective on the evolution of disease-modifying treatments, and then proceeds to provide a discussion on molecular pathophysiology. Next, the factors that contribute to the efficiency of translational medicine are explained. Lastly, the future of disease-modifying therapies is discussed. Interferon beta (IFNβ) was the first effective disease-modifying therapy to become available for MS. The factors that improve the efficiency of translational medicine in MS include: the identification of drug targets within well-validated biological pathways; and the use of pharmacodynamic markers, especially in early proof-of-concept and dose-ranging clinical trials. The continuing accumulation of knowledge and understanding of MS can help to accelerate the developing novel therapies for MS.

This chapter summarizes interferon (IFN) biological effects, its possible mechanisms of action, and the key studies in clinically isolated syndromes (CIS), relapsing remitting multiple sclerosis (RRMS), and progressive MS. Measures of specific IFNβ-induced products, such as oligoadenylate synthetase (OAS), β-2 microglobulin, or neopterin, have been useful in pharmacodynamic studies to determine the magnitude and duration of the IFNβ-response, since serum levels of IFNβ are undetectable following injections. A consistent finding of follow-up studies from the three pivotal IFNβ RRMS trials and two CIS trials is that early treatment is beneficial compared with delayed treatment. IFNβ is partially effective in clinical trial groups. Since approval 18 years ago of the first IFNβ product for RRMS, treatment effects of β at all stages of MS have become fairly clear. The development of β for MS has illustrated many of the challenges in developing treatments for MS.

Disease modifying therapy (DMT) with one of the approved agents should be considered in all patients with active relapsing-remitting multiple sclerosis (RRMS) once the diagnosis of MS is confirmed and in selected patients with a clinically isolated demyelinating syndrome (CIS). Interferon beta modulates T-cell and B-cell function, decreases expression of matrix metalloproteinases reversing blood-brain barrier disruption, and alters expression of cytokines. A series of double-blind, placebo-controlled Phase 3 trials in RRMS supported the benefit of interferon in reducing relapses, disability progression, and MRI lesion activity and accrual. All of the available agents have been reported to reduce relapse rate, magnetic resonance imaging (MRI) lesion activity, and accumulation of disability in RRMS. Patients need to be seen on a regular basis after starting treatment to address potential side effects. This chapter discusses treatment of acute relapses, progressive multiple sclerosis and treatment in special populations including children.

This chapter presents the literature review on disease-modifying therapies (DMT) for children with multiple sclerosis (MS). Four first-line DMTs have been approved for treatment of relapsing-remitting (RR) MS in the adult population. They include glatiramer acetate, interferon beta (IFNB)-1a IM, IFNB-1a SC, and IFNB-1b SC. Large phase III studies showed that chronic administration of recombinant IFNB reduced the number of relapses and slowed progression of physical disability in adult patients with RR MS. Abnormalities in liver function tests (LFTs) may be pronounced in younger children taking interferon. The glatiramer acetate is designed to mimic human myelin basic protein and is postulated to induce the myelin-specific response of suppressor T-lymphocytes and to inhibit specific effector T-lymphocytes. Breakthrough disease is a concern in the pediatric MS population. Proposed consensus criteria for breakthrough disease in adults include increase in relapse number, new or recurrent MRI lesions, and worsening of cognitive or motor disability.