PERSPECTIVES Oral Therapies for Multiple Sclerosis

Multiple sclerosis treatment faces tremendous changes owing to the approval of new medications, some of which are available as oral formulations. Until now, the four orally available medications, fingolimod, dimethylfumarate (BG-12), teriflunomide, and cladribine have received market authorization, whereas laquinimod is still under development. Fingolimod is a sphingosine-1-phosphate inhibitor, which is typically used as escalation therapy and leads to up to 60% reduction of the annualized relapse rate, but might also have neuroprotective properties. In addition, there are three more specific S1P agonists in late stages of development: siponimod, ponesimod, and ozanimod. Dimethylfumarate has immunomodulatory and cytoprotective functions and is used as baseline therapy. Teriflunomide, the active metabolite of the rheumatoid arthritis medication leflunomide, targets the dihydroorotate dehydrogenase, thus inhibiting the proliferation of lymphocytes by depletion of pyrimidines. Here we will review the mechanisms of action, clinical trial data, as well as data about safety and tolerability of the compounds.
Source: Cold Spring Harbor perspectives in medicine - Category: Research Authors: Tags: Multiple Sclerosis PERSPECTIVES Source Type: research

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Authors: Ingawale DK, Mandlik SK Abstract Inflammation is a physiological intrinsic host response to injury meant for removal of noxious stimuli and maintenance of homeostasis. It is a defensive body mechanism that involves immune cells, blood vessels and molecular mediators of inflammation. Glucocorticoids (GCs) are steroidal hormones responsible for regulation of homeostatic and metabolic functions of body. Synthetic GCs are the most useful anti-inflammatory drugs used for the treatment of chronic inflammatory diseases such as asthma, chronic obstructive pulmonary disease (COPD), allergies, multiple sclerosis, te...
Source: Immunopharmacology and Immunotoxicology - Category: Allergy & Immunology Tags: Immunopharmacol Immunotoxicol Source Type: research
Abstract Oxidative stress is the off-balance of antioxidants and free radicals. All kinds of disease and disorders give rise to oxidative damage including autoimmune diseases. An autoimmune disorder is a pathological condition characterized by the breakdown of self-tolerance of the immune system in the body. Immunological processes against tissues and organs leading to enhanced oxidative stress and in turn, misbalance of oxidative stress aggravates the pathobiology of the disease. Highly reactive nature of free radicals, for example, hydroxyl, superoxide ions, alter DNA, protein, and lipids in the body which augme...
Source: Current Protein and Peptide Science - Category: Biochemistry Authors: Tags: Curr Protein Pept Sci Source Type: research
Abstract Numerous epidemiological studies have suggested a link between vitamin D deficiency and the development of various autoimmune diseases, including diabetes mellitus type 1, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis or systemic lupus erythematosus. More recently, such a link has been also proposed for autoimmune bullous diseases (AIBD). This is a relatively rare and potentially life-threatening, organ-specific group of inflammatory skin diseases characterized by the presence of tissue-bound and circulating autoantibodies against various molecules present in desmosomes (in pemphigu...
Source: Acta Biochim Pol - Category: Biochemistry Authors: Tags: Acta Biochim Pol Source Type: research
This article will give a new perspective on understanding immunopathogenesis of autoimmune diseases not only in animals but also in human. Emerging approaches to investigate cytokine regulation through gene modulation may be a potential approach for the tailored immunomodulation of some autoimmune diseases near in the future.
Source: Autoimmunity Reviews - Category: Allergy & Immunology Source Type: research
WEDNESDAY, Feb. 5, 2020 -- A new discovery could lead to better treatments for multiple sclerosis (MS) and other autoimmune diseases, such as psoriasis and rheumatoid arthritis, researchers report. MS occurs when immune cells get into the central...
Source: Drugs.com - Daily MedNews - Category: General Medicine Source Type: news
AbstractPurposeRetinal vasculitis and occlusive changes are important signs of posterior uveitis and are possible diagnostic markers for uveitis. However, the frequency of arteritis and phlebitis in various uveitis entities, including infectious uveitis (IU) and non-infectious uveitis (NIU), have not been systematically investigated.Study designRetrospective.MethodsWe investigated the frequency of retinal vascular inflammatory and occlusive changes in patients with IU and NIU. The study included 283 patients with intermediate, posterior, or pan-uveitis who were diagnosed with IU (presumed tuberculous uveitis, acute retinal...
Source: Japanese Journal of Ophthalmology - Category: Opthalmology Source Type: research
Abstract Acid-sensing ion channels (ASICs) are voltage-independent cation channels that detect decreases in extracellular pH. Dysregulation of ASICs underpins a number of pathologies. Of particular interest is ASIC3, which is recognised as a key sensor of acid-induced pain and is important in the establishment of pain arising from inflammatory conditions, such as rheumatoid arthritis. Thus, the identification of new ASIC3 modulators and the mechanistic understanding of how these compounds modulate ASIC3 could be important for the development of new strategies to counteract the detrimental effects of dysregulated A...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research
We present the preparation and characterization of proteins necessary for investigating the structural interactions of DHODH with the lipids of the IMM, including expression and purification of full-length and N-terminally truncated (without MS and TM) DHODH. We characterized the interaction of truncated DHODH with lipid bilayers containing some key lipids of the IMM using Quartz Crystal Microbalance with Dissipation monitoring and compared it to the DHODH from E. coli, a DHODH that naturally lacks a TM. Our results suggest that although cardiolipin enhances the interaction of truncated DHODH with lipid bilayers, the prese...
Source: Nucleosides, Nucleotides and Nucleic Acids - Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research
Choi The integration of computational techniques into drug development has led to a substantial increase in the knowledge of structural, chemical, and biological data. These techniques are useful for handling the big data generated by empirical and clinical studies. Over the last few years, computer-aided drug discovery methods such as virtual screening, pharmacophore modeling, quantitative structure-activity relationship analysis, and molecular docking have been employed by pharmaceutical companies and academic researchers for the development of pharmacologically active drugs. Toll-like receptors (TLRs) play a vital ...
Source: Molecules - Category: Chemistry Authors: Tags: Review Source Type: research
Purpose of review Th1, Th17, and Treg cells play distinct roles in autoimmune diseases, including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. During the last 5 years we have learned that T-cell metabolism affects cell survival, differentiation and fate of T cells. Recent findings We highlight recent studies which have reported on T-cell metabolism in autoimmune diseases, differences in cellular metabolisms in T-cell subsets among various diseases and transcription factors which control the expression and function of central metabolic enzymes. Summary Distinct metabolic processes cont...
Source: Current Opinion in Rheumatology - Category: Rheumatology Tags: IMMUNOPATHOGENESIS AND TREATMENT OF AUTOIMMUNE DISEASES: Edited by George C. Tsokos Source Type: research
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