H2020Индивидуална стипендия2019–2021

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

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-10-01 → 2021-10-31
Финансиране от ЕС: 162 806 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Токсичните метали (като олово и живак) и протеините от топлинен шок се анализират като рискови фактори за развитие на амиотрофична странична склероза. Това помага да се разбере как околната среда и генетиката влияят върху това фатално невродегенеративно заболяване.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

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

Amyotrophic Lateral Sclerosis (ALS) is a terminal neurodegenerative condition of largely unknown aetiology with an incidence in across Europe of 1 to 3 per 100,000 people and a lifetime risk of approximately 1:300. ALS is invariably fatal with a median survival of approximately 3 years, although a subset of patients have longer survival. ALS typically presents with a history of progressive weakness and the presence of mixed upper and clinically typified by onset muscle wasting, however it is increasingly recognized to also include cognitive and behavioural deficits in some cases. Research of ALS, as the most prevalent motor neurone disease (MND), is prioritized in the EU’s Joint Programme – Neurodegenerative Disease Research(JPND). The cause of ALS remains largely unknown, with the exception of the 10-15% of cases known to have genetic causes. Recent theory suggests that genetic pre-disposition combined with environmental exposures over time result in molecular changes in a stepwise process. Exposure to toxic metals has been frequently suggested as a risk factor for ALS in epidemiological studies and studies of occupational exposure. Toxic metals can affect a wide range of biological processes of relevance in neurodegeneration, and several toxic metals that are of interest in ALS, (cadmium, chromium, lead and mercury), are also listed as priority substances for monitoring and health related research studies by the Human Biomonitoring for Europe (HBM4EU) project. Additionally, toxic metals are known to be an exogenous trigger of the heat shock response, and serum heat shock proteins (HSP’s) have been reported to be elevated in ALS patients. Longitudinal trends of metals and HSP concentrations are likely an important unrecognized factor, and the dynamic nature of toxic metal exposure has been rarely considered in ALS studies. However, to date, data from longitudinal sampling of toxic metal biomarkers in ALS patients, and in healthy individuals, is lacking. The aim of the MetALS study has been to collect single time point as well as longitudinal blood and urine samples from ALS patients and control participants for the purpose of lab measurement of toxic metals and potential ALS biomarkers such as creatinine and heat shock proteins. Subsequent statistical modelling is to be performed to determine if longitudinal trends differ in patients vs controls, to determine the prognostic importance if any of toxic metal concentrations, and to explore longitudinal heat shock proteins concentrations as biomarkers of progression in ALS.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN · PlaneggКоординаторГермания