Biomedical subjects

Siobhan M Leary

Publications and source records attributed to Siobhan M Leary.

5 recordsLinked to original sources

PubMed2005

Primary progressive multiple sclerosis : current and future treatment options.

Approximately 10% of patients with multiple sclerosis (MS) run a primary progressive course characterised by an accumulation of neurological deficits without relapse or remission. Designing therapeutic trials in primary progressive MS (PPMS) has presented several problems. Patient recruitment may be difficult because of the relative rarity of PPMS and historically has been hindered by the lack of specific diagnostic criteria. There has been a limited choice of validated outcome measures, although, in recent studies, the MS functional composite measure and magnetic resonance imaging measures of lesion load and atrophy have been widely used. Despite these problems, several trials have been designed specifically for PPMS, including exploratory randomised controlled trials of interferon-beta-1a and interferon-beta-1b and mitoxantrone, a phase III trial of glatiramer acetate, and an open-label study of riluzole. Patients with PPMS have also been included in randomised controlled trials of azathioprine, methotrexate, cladribine, intravenous immunoglobulin and cyclophosphamide, and open-label studies of haematopoietic stem cell transplantation and pirfenidone in progressive MS. However, no treatment has been proven definitively to modify the course of the disease. Looking to the future, therapeutic agents should aim to target the underlying pathogenic mechanisms in PPMS. As a result of the relative lack of inflammation in PPMS, neuroprotective agents that target neuronal loss directly, rather than inflammation, may be more worthwhile. However, further investigation into the pathogenic mechanisms in PPMS is required to guide the development of future therapeutic agents.

Disease Progression↗

PubMed2004

Serum S100B in primary progressive multiple sclerosis patients treated with interferon-beta-1a.

S100B belongs to a family of calcium-binding proteins implicated in intracellular and extracellular regulatory activities. This study of serum S100B in primary progressive multiple sclerosis (PPMS) is based on data obtained from a randomized, controlled trial of Interferon beta-1a in subjects with PPMS. The key questions were whether S100B levels were associated with either disability or MRI findings in primary progressive MS and whether Interferon beta-1a has an effect on their S100B levels. Serial serum S100B levels were measured using an ELISA method. The results demonstrated that serum S100B is not related to either disease progression or MRI findings in subjects with primary progressive MS given Interferon beta-1a. Furthermore there is no correlation between S100B levels and the primary and secondary outcome measures.

Adult↗

PubMed2004

Overview of London trial of intramuscular interferon-beta Ia in primary-progressive multiple sclerosis.

This short monograph describes the rationale, design and outcome of a pilot study of beta interferon in patients with primary progressive MS. A total of 50 patients were studied for 2 years using a randomized, double-blinded, placebo-controlled design. There was an emphasis on using MRI measures to evaluate outcome. The study showed that with the numbers studied, useful data could be obtained on safety and on efficacy on certain MRI measures. A larger study would be required to evaluate treatment on disability in this patient cohort and further work is needed to elucidate the relationship between quantitative MR and clinical measures over the longer term.

Adjuvants, Immunologic↗

PubMed2003

Interferon beta-1a in primary progressive multiple sclerosis.

There is currently no disease-modifying treatment proven to be of efficacy in primary progressive multiple sclerosis (PPMS). However, a number of therapeutic trials have recently been specifically designed for this group. These include a randomised controlled trial of interferon beta-1a which is discussed here. It is hoped that therapeutics in primary progressive multiple sclerosis will continue to expand and effective therapeutic agents will be developed.

Adjuvants, Immunologic↗

PubMed2003

Serum gelatinase B/MMP-9 in primary progressive multiple sclerosis patients treated with interferon-beta-1a.

BACKGROUND: Interferon- beta (IFNbeta) acts by a variety of mechanisms in relapsing-remitting multiple sclerosis (MS). One of these is a cellular down-regulation of gelatinase B or matrix metalloproteinase-9 (MMP-9), which is known from biochemical, biological and immunohistochemical evidences to play a disease-promoting role in MS. AIMS: a) To investigate the influence of IFNbeta-1a (30 or 60 micro g I. M./week) on serum MMP-9 levels in patients with primary progressive MS (PPMS). b) To correlate serum MMP-9 levels with clinical and magnetic resonance imaging (MRI) findings. METHODS: Serial blood samples were collected every 3 months from 49 patients participating in a phase II trial of IFNbeta-1a in PPMS. Serum MMP-9 was quantified by ELISA and correlations with clinical (EDSS) as well as MRI findings (brain and spinal cord atrophy, ventricular volume, T1 and T2 lesion load) were calculated. RESULTS: No significant differences were found between serial serum MMP-9 levels in IFNbeta-treated versus placebo-treated patients. MMP-9 levels did not differ between patients who progressed or did not progress during the study interval. Although mean absolute serum MMP-9 levels over the study period correlated with an increase in T2 lesion load (relative T2 change: r=0.51, p<0.001; absolute T2 change: r=0.30, p=0.038), absolute increase in brain ventricular volume (r=0.29, p=0.05) and increased brain atrophy (r=0.35, p=0.02), only the correlation with T2 lesion load was sustained throughout the study period. No correlations were found between MMP-9 levels and relative changes in ventricular volume or with relative/absolute changes in T1 lesion load and in spinal cord atrophy. None of the MRI measures correlated with MMP-9 changes between baseline levels and those on treatment. CONCLUSION: Although some evidence suggests a down-regulating effect of IFNbeta on MMP-9, this was not confirmed for a once weekly intramuscular dose of IFNbeta-1a in patients with PPMS. The sustained correlation between serum MMP-9 and changes in T2 volumes, and the lack of correlation with clinical or MRI measures of disease progression may suggest that MMP-9 is more directly related to non-specific central nervous system damage than to axonal loss.

Adult↗