fumaric-acid and Multiple-Sclerosis

Topics: Administration, Oral; Adult; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Fumarates; Humans; Multiple Sclerosis; Psoriasis; Severity of Illness Index; Treatment Outcome

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system and the most common cause of neurological disability in young adults, along with a considerable clinical and pathological heterogeneity. Since, current therapies appear to be modest in the magnitude of their treatment effects, particularly in the progressive phase of this disease, thus novel promising therapeutic strategies might open a light horizon in approaching to an efficient treatment in MS. In this review, we will discuss about relevant patents and novel designed immunosuppressive and anti-inflammatory oral drugs promising for treatment of multiple sclerosis.

Topics: Administration, Oral; Cladribine; Crotonates; Diterpenes; Epoxy Compounds; Fingolimod Hydrochloride; Fumarates; Humans; Hydroxybutyrates; Multiple Sclerosis; Nitriles; Patents as Topic; Phenanthrenes; Propylene Glycols; Quinolones; Sphingosine; Toluidines

Disease-modifying treatments are now available in relapsing-remitting and secondary progressive multiple sclerosis (MS), and their beneficial effects have been shown in several clinical studies. However, as these treatments are only partially effective in halting the MS disease process and are frequently associated with side effects and suboptimal patient adherence, new oral therapeutic approaches are warranted. This review focuses on advances in current and novel oral treatment approaches for MS. Several pivotal reports have provided promising results for new oral therapies evaluating the safety and efficacy of new agents including fingolimod, fumaric acid, cladribine, teriflunomide and laquinimod.

Topics: Cladribine; Clinical Trials, Phase III as Topic; Crotonates; Fingolimod Hydrochloride; Fumarates; Humans; Hydroxybutyrates; Immunosuppressive Agents; Multiple Sclerosis; Nitriles; Propylene Glycols; Quinolones; Sphingosine; Toluidines

Therapy for multiple sclerosis (MS) has changed dramatically over the past decade, yielding significant progress in the treatment of relapsing/remitting and secondary progressive MS. Disease-modifying treatments are now widely available, and their beneficial effects on relapse rates, MRI outcomes and, in some cases, relapse-related disability have been shown in several clinical studies. However, as these treatments are only partially effective in halting the MS disease process and in clinical practice are frequently associated with injection-related side effects and suboptimal patient adherence, new oral therapeutic approaches are warranted.. The aim of the present paper is to present new promising results from emerging oral drugs for multiple sclerosis.. This review focuses on advances in current and novel oral treatment approaches for MS. Nevertheless, most of the data were obtained from Phase I/II clinical trials, we need further confirmation of their safety and efficacy profile from longer Phase III clinical trials.. Several pivotal reports have provided promising results for new oral therapies evaluating the safety and efficacy of new agents including fingolimod, fumaric acid, cladribine, teriflunomide and laquinomid.. It is unknown whether these oral drugs could be used as first-line treatment for MS; this will depend mostly on their safety profile. Alternatively, these drugs could be used as add-on treatment for failed first-line therapy, or as an effective induction agent.

Topics: Administration, Oral; Cladribine; Crotonates; Fingolimod Hydrochloride; Fumarates; Humans; Hydroxybutyrates; Immunosuppressive Agents; Multiple Sclerosis; Nitriles; Propylene Glycols; Quinolones; Sphingosine; Toluidines

Multiple Sclerosis (MS) is an autoimmune-neurodegenerative disorder managed therapeutically by modulating lymphocytes activity which has potential in disease management. Prohibitin 1(PHB) that controls the reactive oxygen species (ROS) and present on the activated lymphocytes have significance in the therapy of MS as esters of fumaric acid that regulates ROS is in phase II/III clinical trials. Thus, we evaluated the expression levels of PHB1 in experimental autoimmune encephalomyelitis (EAE), the animal model of MS and on MS patient's lymphocytes. PHB levels in brain tissue of EAE animals were determined by immunoblotting and on blood lymphocytes from MS relapse, Remission, Optic Neuritis, Neurological controls and Healthy volunteers by FACS using anti-PHB and anti-CD45 antibodies. We observed significant elevation of PHB in EAE brains (91.0 ± 17.59%) vs controls (29.8 ± 12.9%) (p = 0.01) and on lymphocytes of MS patients in acute (73.5 ± 11.20%) or relapsing (69.3 ± 17.33%) phase compared to remission (45.9 ± 8.08%) [p = 0.034 acute vs remission; p = 0.004 relapse vs remission]. Up regulation of PHB in relapsing vs remission MS patients imply the potential use of PHB to clinically evaluate subclinical disease status towards prognosis of an oncoming relapse. Elevated PHB levels in EAE brains signify the role of PHB in regulating ROS and implies PHB's role in oxidative stress.

Topics: Adolescent; Adult; Animals; Brain; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Encephalomyelitis, Autoimmune, Experimental; Female; Fumarates; Humans; Lymphocytes; Male; Mice; Middle Aged; Multiple Sclerosis; Prohibitins; Repressor Proteins; Up-Regulation

Multiple sclerosis (MS) represents the prototypic inflammatory autoimmune disorder of the central nervous system and the most common cause of neurological disability in young adults, exhibiting considerable clinical, radiological and pathological heterogeneity. A better understanding of the immunopathological processes underlying this disease have recently led to the design of numerous novel therapeutical approaches. Perhaps most importantly, therapy has changed dramatically over the past decade in that all relapsing forms of MS, including early forms of MS are now being treated relatively aggressively. However, there are still unmet needs in the management of this disease, especially since all of the currently available disease-modifying drugs are only partially effective. Most of the clinically relevant therapeutic agents are not yet available as oral formulations. A substantial number of pivotal and preliminary reports provide encouraging new evidence on advances being made in the development of oral therapies for MS. A different strategy is the development of very potent monoclonal antibodies, given intravenously or subcutaneously, many of which are being examined for clinical efficacy. These agents are potentially more effective, but may carry more serious side effects. Finally, drugs with a known good safety profile are being developed further. These advances are critically reviewed and put into perspective.

Topics: Administration, Oral; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Cladribine; Crotonates; Fingolimod Hydrochloride; Fumarates; Humans; Hydroxybutyrates; Immunologic Factors; Injections, Intravenous; Injections, Subcutaneous; Interferon-beta; Multiple Sclerosis; Nitriles; Propylene Glycols; Quinolones; Sphingosine; Toluidines