SUJET DE STAGE N° 5
Master 2 R et P : Spécialité MRESTE
Méthodes de Recherche en Environnement - Santé – Toxicologie - Ecotoxicologie
Mention ISM, Ingénieries pour la Santé et le Médicament
Responsable : Pr Anne MAITRE : TIMC-EPSP, UJF/UFR Médecine, CHU Grenoble
Référent Toxicologie et Modélisation : Dominique BICOUT : TIMC-EPSP, UJF/VETAGROSUP Lyon
Référent Ecotoxicologie : Muriel RAVETON : LECA-P3E, UJF/UFR Biologie
SUJET DE STAGE N° 5
Research team and laboratory: EPSP team, TIMC laboratory (UMR 5525), UJF
Universitary supervision: Vincent Bonneterre / Dominique Bicout ([email protected])
For information, a neurologist, Dr Emmeline Lagrange is associated to the project.
Applicant: must have a strong interest in environmental health determinants and Geographic Information
ALS neurodegenerative disease and selenium content in drinking water : investigation of spatial correlations
Disease: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease of the motor system (upper and
lower motoneurones), relentlessly progressive and fatal.
Behind this odd name, “Amyotrophic” refers to the main clinical feature of muscles wasting leading to
progressive paralysis (limbs, speech, swallowing and respiration), and “lateral sclerosis” to the pathological
examination of spinal cord of autopsied patients. Overall population-based lifetime risk of ALS is 1:400 for
women and 1:350 for men. With more classical epidemiological indicators, the incidence is 2.2/ 100 000
person-year in Europe, the peak age about 60. The median survival of 30 months only. Hundred and sixty
years after its description by Charcot, the treatment remains mainly supportive / palliative…
Etiology: the disease still of unknown etiology for 90-95% of the cases that are not familial. Indeed, there is
still controversy about the potential behavioural, occupational and environmental risk factors that have been
studied (Physical activity, Gulf war veterans, selenium in drinking water, heavy metals, « Farming » and «
pesticides », electromagnetic fields, history of electrical shocks, neurotoxins including the cyanotoxin BMAA,
and infectious agents).
Expertise of supervisors: We belong to a consortium which realized (2012) the wider incidence study on ALS
in France, as part of a research project funded by French Research Agency. Our cases were geolocalised and
we were able to identify geographic clusters of ALS patients. We made the hypothesis that clusters could help
to shade the light on places where ALS-related environmental factors, if they exist, could be more easily
brought to the fore. We are currently testing the BMAA hypothesis, and will now test the selenium one
OBJECTIVE. This master’s main objective is to test, if there is a spatial correlation between patient location
and selenium concentrations in drinking water, as this has been described once in a nearby region of Italy.
Secondary objectives are to duplicate the analysis with other trace metals which concentrations are also
Population: 649 ALS cases (2003-2011) from a French area covering 3.1 millions inhabitants (administrative
districts).The file with patients geolocalisation is available.
Exposures: Selenium and other trace metals content in drinking water for each water distribution unit (SISEEAUX database).
Methods and software: Use of geostatistical tools (ArcGis V9 or V10)
A submission of the results in an international scientific journal is expected in June 2014.
Secrétariat pédagogique : [email protected]
UFR de Médecine – Domaine de la Merci – 38706 La Tronche cedex – France - Tél : (0)184.108.40.206.01 – Fax : (0)220.127.116.11.02
KEY WORDS : Geoepidemiology, Ecological study, Selenium, Neurodegenerative disease
Data handling and analyses
Some references :
About Disease: Kiernan et al. Amyotrophic Lateral Sclerosis. Lancet, 2011; 377:942-955
About suspected risk factors, especially Selenium: Vinceti M, et al. Are environmental exposures to
selenium, heavy metals, and pesticides risk factors for amyotrophic lateral sclerosis? Rev Environ
About ALS and Metal hypothesis more generally: Garruto, Yanagihara, Contributions of isolated Pacific
populations to understanding neurodegenerative diseases. Folia Neuropathologica 2009;47(2)149-170
About Selenium content in drinking water in France: ANSES note : « Avis relatif à l’évaluation des
risque sanitaires liés aux dépassement de la limite de qualité du sélénium dans les eaux destinées à la
consommation humaine”. Octobre 2012. Saisine n° 2011-SA-0220