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MetALS SIGNED

Investigating the pharmacokinetic properties of toxic metals and heat shock proteins as risk factors in Amyotrophic Lateral Sclerosis

Total Cost €

EC-Contrib. €

Partnership

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MetALS project word cloud

Explore the words cloud of the MetALS project. It provides you a very rough idea of what is the project "MetALS" about.

307 kinetics 87 metals chromium altered 105 compare background urine liver power metabolism selenium despite ordinary additionally longitudinal construct elimination aluminium odds heat metal controls ratio primarily confirm first sclerosis cohort trend differential statistical hg hsp recruitment function amyotrophic exposure enrolees kidney 15 calculations manganese model correlations confounding combined shock risk zinc models enquiries insights indicate prospective biomarkers methodology fresh meta baseline variables refute inorganic 90 progresses multivariable disease modelled triggered multiple generate toxic prospectively monthly detect turnover protein regression copper bayesian samples bone differences exposures lateral mixed als cadmium repeat employ blood equations measured logistic

Project "MetALS" data sheet

The following table provides information about the project.

Coordinator	LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN Organization address address: GESCHWISTER SCHOLL PLATZ 1 city: MUENCHEN postcode: 80539 website: www.uni-muenchen.de contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Germany [DE]
Total cost	162˙806 €
EC max contribution	162˙806 € (100%)
Programme	1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
Code Call	H2020-MSCA-IF-2018
Funding Scheme	MSCA-IF-EF-ST
Starting year	2019
Duration (year-month-day)	from 2019-10-01 to 2021-09-30

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN Organization address address: GESCHWISTER SCHOLL PLATZ 1 city: MUENCHEN postcode: 80539 website: www.uni-muenchen.de contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	DE (MUENCHEN)	coordinator	162˙806.00

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Project objective

Background: Exposure to toxic metals are proposed as risk factors for amyotrophic lateral sclerosis (ALS). Despite this, evidence remains mixed, with only evidence for lead exposure supported by recent meta-analysis. Many studies neglected that biomarkers may be affected by kidney and liver function. Additionally, the heat shock protein (HSP) response is triggered by toxic metal exposures, and there is evidence for altered HSP metabolism in ALS. Methods: Using available samples (105 ALS cases, 307 controls), blood HSP’s and toxic metal exposures will be measured primarily in urine (inorganic Hg, lead, chromium, aluminium, selenium, zinc, cadmium, copper and manganese). Confounding variables such as kidney and liver function, and bone turnover will be measured. In addition, prospective recruitment of a further 100 cases and 100 controls will be carried out. For prospectively enrolees, repeat blood and urine samples will be taken three-monthly. Statistical analysis: Multivariable logistic regression will be used to compare HSP’s at baseline, while Bayesian models will be used to model correlations between HSP’s and multiple toxic metals. Longitudinal trends will be modelled using Bayesian mixed effects models. Ordinary differential equations will be used to construct elimination kinetics models. Power calculations indicate 90% power to detect an odds ratio of 2.0 at baseline, and 87% to detect longitudinal differences in trend of 15% or more between cases and controls. Impact: MetALS will employ new methodology to generate fresh insights into the role of toxic metals in ALS. MetALS will confirm or refute the finding of HSP’s as biomarkers in ALS, and provide the first insights into longitudinal behaviour of HSP’s as the disease progresses. MetALS will also provide the first combined study of both HSP’s and toxic metal exposure in an ALS cohort. These novel enquiries are expected to provide fresh insights into HSP’s and toxic metal metabolism in ALS.

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