New Treatments For Multiple Sclerosis Research Articles

Involvement of gut microbiota in multiple sclerosis-review of a new pathophysiological hypothesis and potential treatment target.

Multiple sclerosis (MS) is a chronic inflammatory disease that leads to demyelination and damage to the central nervous system. It is well known, the significance of the involvement and influence of the immune system in the development and course of MS. Nowadays, more and more studies are demonstrating that an important factor that affects the action of the immune system is the gut microbiota. Changes in the composition and interrelationships in the gut microbiota have a significant impact on the course of MS. Dysbiosis affects the disease course mainly by influencing the immune system directly but also by modifying the secreted metabolites and increasing mucosal permeability. The essential metabolites affecting the course of MS are short-chain fatty acids, which alter pro- and anti-inflammatory responses in the immune system but also increase the permeability of the intestinal wall and the blood-brain barrier. Dietary modification alone can have a significant impact on MS. Based on these interactions, new treatments for MS are being developed, including probiotics administration, supplementation of bacterial metabolites, fecal microbiota transplantation, and dietary changes. Further studies may serve to develop new drugs and therapeutic approaches for MS.

Gene expression profile and cytokine analysis in experimental autoimmune encephalomyelitis (EAE) in AVP deficient rats

IntroductionHuman Multiple Sclerosis (MS) is a medically important disease. MS and its experimental autoimmune encephalomyelitis (EAE) paradigm are central nervous system demyelinizing diseases in which the immune system is directly involved. The pursuit for new treatments for MS still as an important goal for research. The use of the EAE animals to study the immune mechanisms that mediate the disease still being the best strategy to deep into the immune‐neuroendocrine interactions during the pathogenesis. Previously we have demonstrated that neurointermediate pituitary lobectomy (NIL) decreases humoral and cell‐mediated immune responses and that AVP is directly involved. Nevertheless, the role of AVP has not been entirely clarified.ObjectiveTo investigate the mechanism by which AVP deficiency (by NIL) and desmopressin (DP, a synthetic analog of AVP) affects the development of the clinical signs, the immune response and gene expression profile in the EAE.MethodsFemale Lewis rats were divided into intact control (IC), EAE immunized, NIL and NIL treated with desmopressin (NIL+DP). Except the IC, the remaining groups were immunized for EAE. The EAE was induced by encephalitogen subcutaneous injection. Animals were sacrificed at the peak of the disease (15 days after immunization). EAE clinical signs, cytokine serum profiles (IL‐17A, IL‐4, IL‐2, IL‐10, IL‐6, TNF‐α and INF‐γ) (flow cytometry) and spleen gene expression profile (microarray) were evaluated. DP treatment started 3 days before immunization.ResultsAs compared with the EAE group, NIL animals developed just a mild clinical signs of EAE and significant decreased IFN‐γ and IL‐17 levels. NIL+DP treated animals restored its susceptibility to EAE clinical signs, whereas no‐significant differences on cytokine levels occurred. Significant differences in gene expression profile among groups were evident; in the NIL group the expression pattern of the TGF‐β pathway was down‐regulated as compared with the EAE group, whereas in the NIL+DP group the same genes were up‐regulated.ConclusionsFindings add novel data indicating that directly AVP plays a crucial role in regulating the immune responses and suggests that AVP receptor blockers may be used for the MS treatment and possibly autoimmune diseases and other inflammatory processes.Support or Funding InformationSupported by UAA‐PIFF14‐1 and CONACYT‐221262 (AQS). México. VVB: CONACT Doctoral scholarship. NMS: CONACYT post doctoral Fellow. México.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

On the road to new treatments for multiple sclerosis: targeting dendritic cell migration into the central nervous system.

On the road to new treatments for multiple sclerosis: targeting dendritic cell migration into the central nervous system.

Don't underestimate glial cells

For decades, glial cells languished in relative obscurity. Neurones attracted the interest, kudos and research funding. Here, Mark Greener reports on recent developments in our understanding of the significant role played by glial cells in health and disease. Insights into glial cells' pathological importance and the growing appreciation of their role in normal brain function could offer the prospect of new treatments for multiple sclerosis, Parkinson's and Alzheimer's disease, and many other conditions.

New treatments for multiple sclerosis: at what long-term risk?

New treatments for multiple sclerosis: at what long-term risk?

BCG vaccine for clinically isolated syndrome and MS

Infections may be harmful for people with multiple sclerosis (MS), resulting in fever, “pseudo-exacerbations,” and increased risk of relapses.1 Can infections ever be beneficial for MS? The long-held yet unproven “hygiene hypothesis” proposes that certain infections early in life might reduce the risk of developing autoimmune diseases by inducing protective immunity.2 In addition, parasitic intestinal infections in people with MS may reduce disease activity.3 It follows that better sanitation and common use of disinfectants and antibiotics may account in part for the increased prevalence of MS and other autoimmune diseases in North America and much of Europe, compared with Africa, South America, and parts of Asia. If true, might we harness this natural phenomenon to develop new treatments for MS?

Current and New Directions in MRI in Multiple Sclerosis

This article summarizes the use of MRI in the diagnosis and treatment of multiple sclerosis (MS). Current and emerging imaging techniques are reviewed pertaining to their utility in MS. Conventional T1-weighted and T2-weighted sequences are used to identify and characterize disease pathology in MS. T2 lesion burden, postcontrast enhancement, T1 hypointensities, and regional and global atrophy are all informative and correlate to clinical measures, such as disease disability, to a variable extent. Newer techniques such as diffusion tensor imaging, magnetization transfer imaging, and MR spectroscopy are increasingly being incorporated into clinical trials and may provide improved specificity to the underlying pathology. Double inversion recovery and ultrahigh-field-strength MRI have direct application in MS for evaluating cortical pathology. Newer functional MRI techniques such as resting-state functional connectivity are increasingly being applied in MS. Conventional and emerging imaging techniques greatly inform our understanding of MS. These techniques are integral in diagnosis, in evaluating new treatments for MS, and for following patients in the clinical setting.

Progressive multiple sclerosis: The treatment gap

Most new treatments for multiple sclerosis are for patients with the relapsing–remitting form of the disease. Those with the more advanced, progressive type are being left behind.

Treatment of walking impairment in multiple sclerosis: an unmet need for a disease-specific disability

Introduction: Walking impairment is a clinical hallmark of multiple sclerosis (MS), a chronic neurologic disease characterized by axonal demyelination and dysfunction that results in progressive disability. Until recently, there were no therapies that specifically targeted the axonal dysfunction associated with walking impairment in MS.Areas covered: The purpose of this review is to discuss the unmet need for the treatment of walking impairment in MS patients and to evaluate how a new class of pharmacologic therapies, neurofunctional modifiers, potentially addresses this unmet need. Discussion is based on clinical experience and opinions supported by publications identified in the PubMed literature using the search terms ‘multiple sclerosis’ and ‘mobility OR walking’.Expert opinion: The development and approval of new treatments for MS show promise for improving adherence to therapy and increasing the potential for clinical effectiveness. Renewed emphasis on integrating strategies that target the underlying pathophysiology with those that address symptoms of concern to patients also has the potential to improve the lives of MS patients and their caregivers. The introduction of neurofunctional modifiers, such as dalfampridine for the improvement of walking impairment, may be of benefit by improving function, mobility and overall quality of life for MS patients.

The cost of multiple sclerosis in Norway

Health economic aspects have been increasingly important during introduction of new treatments for multiple sclerosis. As a partial response for Norway, a cost-of-illness study was carried out to estimate the yearly cost of the illness to society and relate costs and patients’ quality of life to illness severity. Estimated cost to society was Euro 439 million in 2002 exclusive of the cost of reduced quality of life. The cost per patient was close to Euro 65,000. Account taken of methodological differences, the results compare to results for Sweden, Norway’s closest neighboring country. The illness reduced patients’ quality of life with 0.26. More patients were early retired because of their MS in Norway than in any of nine other European countries comprised by a recent European study, illustrating a liberal practice in Norway. The Norwegian cost of unpaid assistance was almost identical to the Swedish cost that was the lowest found across the countries in the European study. When related to illness severity, the cost per patient increased, and the patients’ experienced quality of life decreased with increasing EDSS levels in line with what has been found for other countries. Cost-of-MS studies have been carried out for a number of countries. Together they contribute to our understanding of the economic consequences of multiple sclerosis and, if their results are related to illness severity, also provide valuable information for further economic analyses of treatment and medication. Our study adds to this.

SELF-DESTRUCTION STOPPERS

WITH A NEW screening process, researchers have found small molecules that specifi cally bind to the surface of a mouse’s autoreactive T cells, a kind of immune cell that attacks its host. The work could pave the way for new treatments for multiple sclerosis (MS) or other conditions. Most marketed drugs for treating autoimmune diseases such as MS nonselectively adjust immune system function, which can lead to flulike side effects. Searches for more selective agents have focused on finding out what triggers the autoreactive T cells, but these approaches have been slow to bear fruit, says Thomas Kodadek of Scripps Florida. Now, Kodadek and coworkers have developed a screen that doesn’t require that information. They begin with T-cell samples taken from mice with an MS-like condition. The team then isolates autoreactive T cells from the samples and uses them to search for specific binders in a library of synthetic peptoids, which are peptide mimics. The ...

How Does MRI Fit into the MS Diagnostic Picture

Two large clinical trials have demonstrated benefits of new treatments for multiple sclerosis (MS) when given after even a single symptomatic episode in patients with MRI-detected evidence of prior occult disease ( N Engl J Med 2000; 343:898, and Lancet 2001; 357:1576). As a result, the diagnostic emphasis has shifted away from the traditional concept of clinical dissemination in time and space, toward MRI-based assessment. To describe MRI criteria for MS, a panel of experts chaired by E.M. …

New treatments for multiple sclerosis.

New treatments for multiple sclerosis.

Improving Health Care Delivery for Persons with Multiple Sclerosis

Persons with multiple sclerosis (MS) have a close-to-normal life span and can look forward to a high level of consumption of health care services for an average of 40 to 50 years. As expensive new treatments for MS are developed and better rehabilitation techniques are implemented, lifetime health care costs for MS patients can be very great. This article discusses ways in which these costs can be managed.

MS Forum Satellite Symposium, New Treatments for Multiple Sclerosis A Review of Clinical Trials Results

MS Forum Satellite Symposium, New Treatments for Multiple Sclerosis A Review of Clinical Trials Results

New treatments for multiple sclerosis

The steady flow of potential new treatments for multiple sclerosis continues with data resulting from studies ranging in complexity from early pilot trials to phase three studies. While this is in itself encouraging, interpretation of the data presented, and in particular evaluation of the potential clinical usefulness of an agent, is often less than straightforward. Improved understanding of the immunopathogenesis of multiple sclerosis and better trial design incorporation more appropriate and responsive outcome measures should be grounds for continuing therapeutic optimism.

Telling your patient he/she has multiple sclerosis

It is difficult to tell a person that s/he has multiple sclerosis. The diagnosis is based on clinical findings and often cannot be made on first meeting. In many cases investigations do not help. When the diagnosis is made, the patient should be fully informed in the majority of cases. Guidelines have been developed for imparting the diagnosis. Early diagnosis will become increasingly important with the development of new treatments for multiple sclerosis.

New treatments for multiple sclerosis

Encouraging progress has been made in the development of treatments that reduce disease activity in multiple sclerosis. The relation between disability and such activity (as reflected in the relapse rate or the appearance of new lesions on magnetic resonance imaging) is complex, but recent evidence suggests that it may be possible to delay, though not yet abolish, the progress of irrecoverable neurological deficit. The results of three large randomised controlled trials in ambulant patients with little or moderate disability have been announced during the past 18 months. Only one has been fully reported in the medical literature,1 but two others were widely discussed at a joint meeting of the American Neurological Association and the Association of British Neurologists held last October. Because much uncertainty exists about the potential role of these very expensive treatments it is important that the present position is clearly understood. In the review that follows, the figures for the two recent reports have been derived from information provided by the sponsors of the trials2 3; the data on which the conclusions of these two studies are based have yet to be subjected to peer review. In a trial of interferon beta-1b 372 patients with relapsing and remitting disease were allocated to placebo or a low dose (1.6 MIU) or high dose (8 MIU) of the drug, which was given by subcutaneous injection on alternate days. After two years the relapse rate (the primary end point) was significantly lower in patients receiving the high dose than in those receiving placebo (1.27/year …

Magnetic resonance in monitoring the treatment of multiple sclerosis.

Magnetic resonance imaging (MRI) is increasingly being used as a measure of pathological disease activity in monitoring the efficacy of potential new treatments for multiple sclerosis. A major advantage of MRI over clinical monitoring is that it detects a large amount of subclinical disease activity. The two main approaches to MRI are detecting active lesions and measuring total lesion load. In relapsing-remitting and secondary-progressive multiple sclerosis, gadolinium enhancement increases the number of detectable active lesions and also probably correlates with pathological activity. Total brain-lesion load can be measured from computerized images, either by manual outlining of lesions or by more fully automated lesion-segmentation strategies. An important limitation of MRI monitoring is that conventional brain MRI abnormalities often show little or no relationship with clinical disability. One explanation for this may be pathological heterogeneity of lesions that all look the same on a conventional image. Other MR techniques are needed that specifically identify the pathological features most likely to result in disability, namely demyelination and axonal loss. Magnetization transfer imaging and proton MR spectroscopy are two techniques that show promise in this regard.