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.
