Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9BWK5 (MRI)
 85,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Corticosteroids, corticotropin, azathioprine, cyclophosphamide, and IFN-beta 1b have each had a substantial effect on the care of patients with multiple sclerosis and the design of subsequent clinical trials of experimental therapeutics for MS. The use of MRI scanning and more sensitive clinical outcome measures will possibly enable us to complete clinical trials in a fraction of the time required for earlier trials. The release of Betaseron, which favorably alters the attack rate in ambulatory patients with relapsing-remitting MS has brought a sense of renewed optimism to patients with MS, their families, and their care providers. New promising therapies for chronic progressive MS and biologic products possibly capable of enhancing the effects of IFN-beta 1b in patients with relapsing MS are setting the stage for additional important therapeutic advances in this disease.
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PMID:Role of steroids and immunosuppression and effects of interferon beta-1b in multiple sclerosis. 797 69

Interferon beta-1b (IFN beta-1b) (Betaseron) has been recently approved for treatment of multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS). The mechanism of action of IFN beta-1b is not understood, but its effect in reducing gadolinium enhanced MRI lesions suggest an effect at the blood brain barrier (BBB). Thus the objective of this study is to examine the effect of IFN beta-1b treatment of endothelial cells (EC) on lymphocyte-EC adhesion, and on the expression of the adhesion molecules (AM) ICAM-1, VCAM and E-selectin induced by IFN-gamma, TNF-alpha, or IL-1 beta. Primary cultures of human umbilical vein EC (HUVEC) were used which under basal conditions expressed low levels of ICAM-1 but not VCAM or E-selectin. IFN beta-1b (1-1000 IU/ml) had minimal effect on basal expression of AM on HUVEC, but AM could be substantially upregulated by IFN-gamma, IL-1 beta or TNF-alpha which was associated with a parallel increase in lymphocyte-EC adhesion. The effect of IFN beta-1b on AM expression induced by IFN-gamma, IL-1 beta or TNF-alpha was slightly additive, and was associated with a modest increase in lymphocyte-EC adhesion. In contrast TGF-beta, shown previously to downregulate lymphocyte-EC adhesion, inhibited this adhesion in our experiments. It is concluded that IFN-beta does not downregulate the inducible expression of ICAM-1, VCAM or E-selectin on HUVEC and does not inhibit the adhesion of lymphocytes to HUVEC. These findings have implications on the mechanism of action of IFN beta-1b in MS.
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PMID:The effect of interferon beta-1b on lymphocyte-endothelial cell adhesion. 898 22

Interferon beta 1b (Betaseron) was licensed by the U.S. Federal Food and Drug Administration in July 1993 as the first treatment to alter the natural history of multiple sclerosis (MS). The drug, injected subcutaneously every other day, reduced the frequency of relapses and the expansion of central white matter pathology as measured by MRI. Twelve previous interferon trials in MS, employing a variety of interferon preparations, doses and routes of administration, preceded this trial and provided the scientific foundation for its success. Beta interferon therapy probably inhibits gamma interferon to achieve its therapeutic effect. Future MS therapy may require combination treatment with multiple agents with complimentary immunologic effects.
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PMID:Role of interferons in demyelinating disease. 926 20

Interferon beta-Ib (Betaseron) has been shown in a randomized, double-blind, placebo-controlled study to reduce relapse rate, relapse severity and MRI progression in patients with relapsing-remitting MS. The recently published Betaseron extension trial and studies from the National Institutes of Health provide additional evidence suggesting an important treatment effect. The major new findings from these studies are reviewed in this paper. Other findings from these recent studies merit attention, however. Specifically, neutralizing antibody formation was seen in 38% of patients receiving high-dose Betaseron at 3 years. With the development of these antibodies, there was no longer clinical evidence that the drug remained effective. This observation must be considered carefully when initiating Betaseron therapy. The Betaseron trial suggests that MRI is an imperfect predictor of clinical disease activity. Of particular interest was the finding that patients receiving low-dose Betaseron developed 'confirmed treatment failure' sooner than placebo-treated patients, despite a clear treatment benefit on MRI-detected evidence of subclinical disease activity.
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PMID:Interferon beta-1b: latest published results, 1995. 934 6

Doctors Noseworthy and Summerfield have reviewed the results of placebo-controlled, double-masked, clinical trials of interferon beta-1b (IFNB-1b, Betaseron) and interferons beta-1a (IFNB-1a, Avonex,) in patients with relapsing multiple sclerosis (MS). IFNB-1b, administered subcutaneously every other day to ambulatory patients with relapsing-remitting MS, significantly reduces annual exacerbation rate and percentage change from baseline MRI T2-weighted total lesion area. There is also evidence that IFNB-1b reduces the number of new gadolinium-enhancing lesions in patients with relapsing-remitting MS. IFNB-1a (Avonex), administered intramuscularly every week to patients with relapsing MS, significantly reduces annual exacerbation rate, the number and volume of new focal gadolinium-enhanced T1-weighted lesions, and slows the accumulation of physical disability over time. However, questions remain regarding the efficacy of these treatments, the significance of neutralizing antibody formation, indications for therapy, adverse events, optimal dose, and route of administration. Design limitations of the Phase III trial of IFNB-1b have been reviewed elsewhere, and a critical review of the results of the Phase III trial of IFNB-1a should be undertaken after the publication of the clinical and imaging results of that study.
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PMID:Interferon beta treatment for multiple sclerosis: persisting questions. 934 8

Three interferon beta preparations (Betaseron, Avonex, and Rebif) have shown efficacy in the treatment of relapsing-remitting multiple sclerosis (MS). Attack frequency is reduced by 30% and major attacks to an even greater extent. Accumulating disease burden as measured by annual T2-weighted magnetic resonance imaging is markedly lessened, and disease activity as measured by serial gadolinium-enhanced MRI scanning is reduced by over 80%. A fourth preparation, Copaxone, a basic copolymer of four amino acids, lessens MS attack frequency by 30% and also lessens disease activity as measured by gadolinium-enhanced MRI. Betaseron lessens accumulation of disability in MS patients with secondary progressive disease regardless of the severity of disability at the time treatment is commenced. MS is now a treatable disease.
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PMID:Immunologic therapy of multiple sclerosis. 1007 79

Autoimmune diseases such as multiple sclerosis are characterized by complex genetic traits and pathomechanisms that translate into clinical heterogeneity. This wide heterogeneity of multiple sclerosis as well as different biological responses to immunomodulatory drugs can be expected to contribute to differential treatment responses. Strategies that dissect the relationship between the treatment response and the biological characteristics in individual patients are valuable not only as a clinical tool, but also in leading to a better understanding of the disease. Here we address the in vitro and ex vivo RNA expression profile under one approved therapy of multiple sclerosis, interferon-beta (IFN-beta, Betaseron), by cDNA microarrays and demonstrate that non-responder and responder phenotypes to IFN-beta as assessed by longitudinal gadolinium-enhanced MRI scans and clinical disease activity differ in their ex vivo gene expression profile. These findings will help to better elucidate the mechanism of action of IFN-beta in relation to different disease patterns and eventually lead to optimized therapy.
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PMID:Expression profiling identifies responder and non-responder phenotypes to interferon-beta in multiple sclerosis. 1276 62

Early therapeutic intervention with disease modifying agents in multiple sclerosis (MS) is recommended in an attempt to minimise damage to the central nervous system and improve clinical outcome. Interferon betas (IFN betas) are the most widely used approved therapies for MS at the present time. While optimal dosage and frequency of IFN administration is not fully known, evidence is growing that high-dose, high-frequency IFN beta may be the most effective regimen for controlling clinical activity and minimizing MRI lesion development for at least 1-2 years. Past experience demonstrates that commonly observed side-effects associated with IFN beta injections, such as flu-like symptoms and injection-site reactions, can be markedly reduced through a number of measures. Moreover, the incidence of these side-effects decreases with time. Taking these observations into account, it seems reasonable to consider increasing the maximum approved therapeutic dose of IFN beta-1b (Betaferon/Betaseron) in MS. It has recently been demonstrated that dose escalation of IFN beta-1b combined with pre-medication with ibuprofen enables doses as high as 500 microg every other day to be well tolerated. Further administration of IFN beta-1b (500 microg) in patients with hepatitis C revealed no safety or tolerability concerns, no unexpected or unusual symptoms and no relevant laboratory abnormalities during the 24-week treatment period. It is also noteworthy that the 500 microg dose produced a more marked increase in biological response markers (Mx protein) than that induced by the standard dose of IFN beta-1b, and that other studies have demonstrated similar effects on other such markers. Taken together, the available evidence provides a rationale for using an increased dose of IFN beta-1b in the treatment of MS. This will be investigated further in a new Phase III clinical trial (BEYOND).
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PMID:Advancing treatment with interferon beta-1b (Betaferon/Betaseron) in the next decade--thinking beyond the standard dose. 1471 97

Immunosuppressants have been proposed as disease-modifying treatments in multiple sclerosis (MS) for almost 40 years, but only one, mitoxantrone, has recently been approved, whereas beta-interferons and glatiramer acetate have been licensed since the mid-90s. Recent therapeutic trials of potent immunosuppressive agents such as Campath-1H, mitoxantrone and cyclophosphamide of MS patients with high relapse rates, rapid accumulation of disability and high degree of MRI activity, have resulted in strong suppression of clinical and MRI inflammatory activity, provided that profound and prolonged lymphopenia was achieved. Clinical experience during the past decades has amply demonstrated that some patients with MS respond to immunosuppressants. The odds ratios of relapsing-remitting MS patients to remain relapse-free after a 2-year period of treatment are similar for Betaseron, Avonex, Rebif, Copaxone, intravenous immunoglobulins or azathioprine compared to placebo. The risk of cancer induction is not significant for up to 10 years of daily usage of azathioprine. Currently available non-specific immunosuppressants are able to control inflammation and reduce relapses in MS, but cannot prevent neurodegeneration and the progression of irreversible disability; specific tools need to be developed for that purpose.
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PMID:Non-specific immunosuppressants in the treatment of multiple sclerosis. 1517 81

Multiple sclerosis (MS) is a complex, incurable disease. Treatment consists of lifelong disease and symptom management. FDA-approved therapies for relapsing MS include subcutaneous (SC) interferon beta-1b (IFNbeta1b, Betaseron), IM interferon-beta-1a (Avonex), SC interferon-beta-1a (Rebif), glatiramer acetate (Copaxone), and mitoxantrone (Novantrone), all of which are known as disease-modifying agents (DMAs). DMAs that can be initiated and continued on a long-term basis can be referred to as platform therapies. During periods of disease instability with increased disease activity, corticosteroids or immunosuppressive agents can be used in combination with appropriate DMA platform therapy to help control symptoms. To date, long-term comparative studies of DMAs are not available. However, based on the effects of these agents on disability progression, relapse rates, MRI outcomes, and neutralizing antibodies observed in phase III randomized clinical trials, IFNbeta1a products are the DMAs of choice for platform therapy for MS. Evidence indicates that IFNbeta1a may also be beneficial in the early stages of the disease. Research is ongoing to identify other appropriate add-on agents (e.g., antigen-specific therapies) to be used in combination with existing DMAs to effectively manage MS.
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PMID:Selecting a disease-modifying agent as platform therapy in the long-term management of multiple sclerosis. 1559 32


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