Relapse Rate In Multiple Sclerosis Research Articles

A review of the natural history and epidemiology of multiple sclerosis: implications for resource allocation and health economic models.

A review of the natural history and epidemiology of multiple sclerosis: implications for resource allocation and health economic models.

Ovine IFN-tau modulates the expression of MHC antigens on murine cerebrovascular endothelial cells and inhibits replication of Theiler's virus.

Interferon-beta (IFN-beta) has been used successfully to treat patients with relapsing-remitting multiple sclerosis (MS). IFN-tau is a new class of type I IFN that is secreted by the trophoblast and is the signal for maternal recognition of pregnancy in sheep. IFN-tau has potent immunosuppressive and antiviral activities similar to other type I IFN but is less cytotoxic than IFN-alpha/beta. The current investigation concerns the effect of recombinant ovine IFN-tau (rOvIFN-tau) on the modulation of MHC class I and II expression on cloned mouse cerebrovascular endothelial (CVE) cells. IFN-tau induced tyrosine phosphorylation of Stat1 and upregulated the expression of MHC class I on CVE. One proposed action by which type I IFN reduce the relapse rate in MS is via interference with IFN-gamma-induced MHC class II expression. IFN-tau was shown to downregulate IFN-gamma-induced MHC class II expression on CVE and, hence, may be of potential therapeutic value in downregulating inflammation in the central nervous system (CNS). IFN-tau did not upregulate the expression of MHC class II on CVE. IFN-tau also inhibited the replication of Theiler's virus in CVE. These in vitro results suggest that IFN-tau may be of therapeutic value in the treatment of virus-induced demyelinating disease.

Systemic disease and neuro-ophthalmology: annual update 2000 (Part I).

Multiple sclerosis (MS) is a common demyelinating disease of the central nervous system (1–86), with substantial long-term neurologic consequences (1,4,9,25,34, 52,54,55,57,60,63,65). After 10 years with MS, 50% of patients are unable to perform household and occupational responsibilities; after 15 to 20 years, 50% are unable to walk without assistance; after 25 years, 50% are unable to ambulate. The average annual cost of MS in the United States is greater than 6.8 billion dollars (1). There are three main subtypes of the disease: relapsing remitting (RR), secondary progressive (SP), and primary progressive (PP). This update reviews the current status of MS therapy (1–86). We have chosen to focus on the new and emerging immunomodulatory therapies for disease relapses and the treatments to prevent disease progression. We do not review the treatments for common MS-related sensory and motor symptoms, fatigue, or depression (35).

Copolymer 1 acts against the immunodominant epitope 82-100 of myelin basic protein by T cell receptor antagonism in addition to major histocompatibility complex blocking.

The synthetic random amino acid copolymer Copolymer 1 (Cop 1, Copaxone, glatiramer acetate) suppresses experimental autoimmune encephalomyelitis, slows the progression of disability, and reduces relapse rate in multiple sclerosis (MS). Cop 1 binds to various class II major histocompatibility complex (MHC) molecules and inhibits the T cell responses to several myelin antigens. In this study we attempted to find out whether, in addition to MHC blocking, Cop 1, which is immunologically cross-reactive with myelin basic protein (MBP), inhibits the response to this autoantigen by T cell receptor (TCR) antagonism. Two experimental systems, "prepulse assay" and "split APC assay," were used to discriminate between competition for MHC molecules and TCR antagonism. The results in both systems using T cell lines/clones from mouse and human origin indicated that Cop 1 is a TCR antagonist of the 82-100 epitope of MBP. In contrast to the broad specificity of the MHC blocking induced by Cop 1, its TCR antagonistic activity was restricted to the 82-100 determinant of MBP and could not be demonstrated for proteolipid protein peptide or even for other MBP epitopes. Yet, it was shown for all the MBP 82-100-specific T cell lines/clones tested that were derived from mice as well as from an MS patient. The ability of Cop 1 to act as altered peptide and induce TCR antagonistic effect on the MBP p82-100 immunodominant determinant response elucidates further the mechanism of Cop 1 therapeutic activity in experimental autoimmune encephalomyelitis and MS.

Complex immunoregulatory events during pregnancy may explain reduced relapse rate in multiple sclerosis

Complex immunoregulatory events during pregnancy may explain reduced relapse rate in multiple sclerosis

New treatments and azathioprine in multiple sclerosis

Several new drug treatments to reduce the relapse rate in multiple sclerosis (MS) have recently emerged. 1 Johnson KP Brooks BR Cohen JA et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicentre, double-blind, placebo-controlled trial. Neurology. 1995; 45: 1268-1276 Crossref PubMed Scopus (1776) Google Scholar , 2 Jacobs LD Cookfair DL Rudick RA et al. Imtramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol. 1996; 39(3): 285-294 Crossref Scopus (2358) Google Scholar , 3 The IFNB Multiple Sclerosis Study GroupInterferon beta-1b is effective in relapsing-remitting multiple sclerosis. Clinical results of a multicenter, randomised, double-blind, placebo-controlled trial. Neurology. 1993; 43: 655-661 Crossref PubMed Google Scholar , 4 Fazekas F Deisenhammer F Strasser-Fuchs S Nahler G Mamoli M for the Austrian Immunoglobulin in Multiple Sclerosis Study GroupRandomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Lancet. 1997; 349: 589-593 Summary Full Text Full Text PDF PubMed Scopus (386) Google Scholar These drugs are expensive, have to be given by injection, their long-term side-effects are not yet known, and definite evidence of a clear effect on progression of disability is lacking. The use of magnetic resonance imaging (MRI) to study disease activity in recent trials may have been important in the licensing of new drugs. The pharmaceutical industry has also strongly promoted relapse-reduction as an important treatment outcome in MS.

The historical development of interferons as multiple sclerosis therapies.

Human interferon (IFN) beta is the first therapeutic agent to convincingly reduce the multiple sclerosis relapse rate and retard disability. To achieve this significant treatment advance over 15 years of preliminary work was necessary, encompassing over 15 controlled trials which employed each of the three human interferons. Important insights into the pathogenesis of multiple sclerosis (MS) were gained, especially from the findings of the single IFN-gamma trial. This short history describes the unfolding of our current understanding of the place for IFNs in the management of MS. The contribution of the patients who have participated is recognized and their courage acknowledged. The final role for IFN treatment of MS is unclear, but future studies will be required to define the best IFN, optimal dose, and route of administration and patient selection for long-term management of MS.

Azathioprine reduces relapse rates in multiple sclerosis

Azathioprine reduces relapse rates in multiple sclerosis

Pregnancy and Multiple Sclerosis

The effect of pregnancy on the relapse rate of multiple sclerosis has been investigated. Obstetric and relapse histories of 52 women with clinically definite multiple sclerosis were obtained; there were 101 pregnancies of which 85 were at risk of a multiple sclerosis relapse. By comparing the number of relapses in the pregnancy period (9 months of pregnancy and 6 months immediately post partum) with the number in non-pregnancy periods for the same women, no increased risk of relapse during the pregnancy period was demonstrated. However, of the relapses that did occur during the pregnancy period, there was a significant reduction in the number of relapses in the first and second trimesters.

Pregnancy and multiple sclerosis.

The effect of pregnancy on the relapse rate of multiple sclerosis has been investigated. Obstetric and relapse histories of 52 women with clinically definite multiple sclerosis were obtained; there were 101 pregnancies of which 85 were at risk of a multiple sclerosis relapse. By comparing the number of relapses in the pregnancy period (9 months of pregnancy and 6 months immediately post partum) with the number in non-pregnancy periods for the same women, no increased risk of relapse during the pregnancy period was demonstrated. However, of the relapses that did occur during the pregnancy period, there was a significant reduction in the number of relapses in the first and second trimesters.