Novel Therapeutic Approaches to Autoimmune Demyelinating Disorders

Abstract

Multiple Sclerosis (MS) is the most common autoimmune demyelinating disorder in Western countries and can lead to permanent disability. Over the past decades remarkable progress has been made in providing new therapeutic strategies to tackle the burden of the disease. Oral drugs and monoclonal antibodies are the main innovative approaches that have been tested in advanced stage clinical trials. Several new drugs have been shown to be superior to traditional disease modifying treatments (DMTs), in terms of both clinical and imaging outcome measures. Oral drugs have the advantage of offering a convenient route of administration. Recently fingolimod has received approval for the treatment of relapsing remitting (RR)-MS in several countries, becoming the first oral drug available to patients. Whilst the majority of the current studies focus on RR-MS, some trials investigate the primary or secondary progressive subtypes as well as the early forms of the disease aiming at delaying the conversion to clinically definite MS. Overall the future of the treatment options looks promising, although the occurrence of significant adverse events in some instances points to cautious evaluation of risks and benefits. Extension studies for most of the new drugs are under way and will provide evidence on the efficacy and long term effects of the new treatment strategies.

Multiple Sclerosis: Immunopathology and Treatment Update

“…In addition, teriflunomide exerts anti-inflammatory properties by inhibiting IFN-gamma producing T cells while IL-4 and IL-10 producing T cells are unaffected [125]. In MS, oral administration of teriflunomide reduced relapse rates, MS lesions and decreased disability progression [126][127][128][129][130][131]. Moreover, permanent discontinuation due to side effects was substantially less common in MS patients who received teriflunomide compared to IFN-β-1a.…”

Molecular Biomarkers in Multiple Sclerosis

“…Biomarkers not only need to show strong and significant correlation to a specific endpoint, but also have to cover the sum of actions that finally leads to the correlated clinical parameter. Both in combination make it difficult to prove surrogacy for a measured molecular or cellular marker [13]. Furthermore, in MS we have a very diverse range of features making the disease individual for each patient.…”

“…However, about one third of RRMS patients show an insufficient response to these drugs [11,12]. Today, several new treatment options are approaching approval [13,14]. Biomarkers that help in the early estimation of the individual patients' treatment response would be a great improvement for patient care [15][16][17].…”

Pharmacokinetic Bioequivalence Study of Two Formulations of Teriflunomide in Healthy Male Volunteers under Fasting Conditions

“…In addition, teriflunomide exerts anti-inflammatory properties by inhibiting IFNgamma producing T cells while IL-4 and IL-10 producing T cells are unaffected [8]. In MS, oral administration of teriflunomide reduced relapse rates, MS lesions and decreased disability progression [9][10][11][12][13].…”