Challenge of progressive multiple sclerosis therapy

Thompson, Alan J.

doi:10.1097/wco.0000000000000453

Cited by 22 publications

(18 citation statements)

References 27 publications

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“…This is the first unequivocal confirmation that aluminium is increased in brain tissue in MS (Mold et al 2018b) and it further supports the contention that the body burden of aluminium is elevated in MS compared to individuals without MS (Exley et al 2006;Jones et al 2017). The data do not prove a role for aluminium in MS, but a higher content of a neurotoxin and powerful pro-oxidant (Verstraeten et al 1997;Exley 2004) in brain tissue in MS cannot be discarded as a putative aetiological factor in a disease with both genetic and environmental components (Thompson 2017). The results also have translational aspects in that they support previous research in which silicon-rich mineral waters were suggested as potential long-term therapies in treating MS (Jones et al 2017).…”

Section: Discussionsupporting

confidence: 65%

Aluminium in Brain Tissue in Non-neurodegenerative/Non-neurodevelopmental Disease: A Comparison with Multiple Sclerosis

et al. 2020

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Human exposure to aluminium is a burgeoning issue. The brain is a sink for systemically available aluminium and a putative target of neurotoxicity. An increasing number of studies continue to confirm the presence of aluminium in human brain tissue though primarily in relation to donors who have died of a neurodegenerative or neurodevelopmental disorder. Herein, we have measured aluminium in brain tissue in donors who died of a specific disease or condition though without showing any neurodegeneration. The donors were diagnosed as not suffering from multiple sclerosis. Herein, these novel data are compared with recent data on aluminium in brain tissue in multiple sclerosis. Brain tissues from all four lobes were obtained from the Multiple Sclerosis Society Tissue Bank. Tissues were digested using microwave-assisted acid digestion and their aluminium content was measured by transversely heated graphite furnace atomic absorption spectrometry. Both are established methods in our laboratory. Detailed statistical analyses were used to compare new data with recent data for multiple sclerosis. Aluminium was found in brain tissue in each donor with a high proportion of measurements (189/291) being below 1.00 μg/g dry weight. The data for all cases (median and IQR) were 0.74 (0.48-1.28), 1.23 (0.62-1.63), 0.84 (0.45-1.14) and 1.01 (0.62-1.65) μg/g dry weight for occipital, parietal, temporal and frontal lobes, respectively. There was a statistically significant positive correlation between aluminium content of brain tissue and the age of donor. Comparison of data for this non-multiple sclerosis group with brain aluminium data for donors dying with a diagnosis of multiple sclerosis showed that the latter had a statistically significant higher content of brain aluminium. The data reinforce a previous conclusion that the aluminium content of brain tissue in multiple sclerosis is elevated and support the suggestion that human exposure to aluminium may have a role to play in the aetiology of multiple sclerosis. Keywords Human exposure to aluminium • Aluminium in brain tissue • Aluminium in multiple sclerosis • Aluminium and neurodegenerative disease • Aluminium and neurodevelopmental disease Electronic supplementary material The online version of this article (

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Section: Discussionsupporting

confidence: 65%

Aluminium in Brain Tissue in Non-neurodegenerative/Non-neurodevelopmental Disease: A Comparison with Multiple Sclerosis

et al. 2020

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“…(2) The disease affects about 120,000 people in the United Kingdom (UK) with an incidence that appears to be increasing by approximately 2.5% per annum (4). There is a notably significant societal and global burden of £3bn/year (3) In order to comprehensively map the prevalence and characteristics of MS across the UK, the MS Society commissioned Swansea University Medical School, home to the Secure Anonymous Information Linkage (SAIL) Databank (4), to develop the UK Multiple Sclerosis Register (UKMSR). The SAIL databank is a safe haven for billions of person-based records combined with a complete data linkage and an analysis toolset.…”

Section: Introductionmentioning

confidence: 99%

Validating the portal population of the United Kingdom Multiple Sclerosis Register

Middleton

Rodgers

Chataway

et al. 2018

Multiple Sclerosis and Related Disorders

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The UK Multiple Sclerosis Register (UKMSR) is a large cohort study designed to capture 'real world' information about living with multiple sclerosis (MS) in the UK from diverse sources. The primary source of data is directly from people with Multiple Sclerosis (pwMS) captured by longitudinal questionnaires via an internet portal. This population's diagnosis of MS is self-reported and therefore unverified. The second data source is clinical data which is captured from MS Specialist Treatment centres across the UK. This includes a clinically confirmed diagnosis of MS (by Macdonald criteria) for consented patients. A proportion of the internet population have also been consented at their hospital making comparisons possible. This dataset is called the 'linked dataset'. The purpose of this paper is to examine the characteristics of the three datasets: the self-reported portal data, clinical data and linked data, in order to assess the validity of the self-reported portal data. The internet (n = 11,021) and clinical (n = 3,003) populations were studied for key shared characteristics. We found them to be closely matched for mean age at diagnosis (clinical = 37.39, portal = 39.28) and gender ratio (female %, portal = 73.1, clinical = 75.2). The Two Sample Kolmogorov-Smirnov test was for the continuous variables to examine is they were drawn from the same distribution. The null hypothesis was rejected only for age at diagnosis (D = 0.078, p < 0.01). The populations therefore, were drawn from different distributions, as there are more patients with relapsing disease in the clinical cohort. In all other analyses performed, the populations were shown to be drawn from the same distribution. Our analysis has shown that the UKMSR portal population is highly analogous to the entirely clinical (validated) population. This supports the validity of the self-reported diagnosis and therefore that the portal population can be utilised as a viable and valid cohort of people with Multiple Sclerosis for study.

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“…Despite some progress, advances in understanding the pathogenesis of MS remain frustratingly slow [1]. Effective treatments for MS are rare [2,3]. The consensus remains that MS is likely to involve both genetic and environmental factors acting either in isolation or together in various disease phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Aluminium in Brain Tissue in Multiple Sclerosis

Mold

Chmielecka

Rodriguez

et al. 2018

IJERPH

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Multiple sclerosis (MS) is a devastating and debilitating neurodegenerative disease of unknown cause. A consensus suggests the involvement of both genetic and environmental factors of which the latter may involve human exposure to aluminium. There are no data on the content and distribution of aluminium in human brain tissue in MS. The aluminium content of brain tissue from 14 donors with a diagnosis of MS was determined by transversely heated graphite furnace atomic absorption spectrometry. The location of aluminium in the brain tissue of two donors was investigated by aluminium-specific fluorescence microscopy. The aluminium content of brain tissue in MS was universally high with many tissues bearing concentrations in excess of 10 μg/g dry wt. (10 ppm) and some exceeding 50 ppm. There were no statistically significant relationships between brain lobes, donor age or donor gender. Aluminium-specific fluorescence successfully identified aluminium in brain tissue in both intracellular and extracellular locations. The association of aluminium with corpora amylacea suggests a role for aluminium in neurodegeneration in MS.

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Challenge of progressive multiple sclerosis therapy

Abstract: Raising the profile of progressive MS has resulted in the first effective treatments with the promise of more to come.

Cited by 22 publications

References 27 publications

Aluminium in Brain Tissue in Non-neurodegenerative/Non-neurodevelopmental Disease: A Comparison with Multiple Sclerosis

Aluminium in Brain Tissue in Non-neurodegenerative/Non-neurodevelopmental Disease: A Comparison with Multiple Sclerosis

Validating the portal population of the United Kingdom Multiple Sclerosis Register

Aluminium in Brain Tissue in Multiple Sclerosis

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