Alexis Elbaz: Fighting Parkinson’s disease head on

Alexis Elbaz is a neurologist and Inserm research director. His goal? For Parkinson’s to be a thing of the past. Through the discovery of risk factors or protective factors, his research provides data to envisage the prevention of a disease whose prevalence is increasing with population ageing.

In France, Alexis Elbaz is a key figure in Parkinson’s disease research. His many studies contribute to informing the international community about its risk factors, its environmental and genetic links, and its inexorable progression with population ageing. Parkinson’s is the second most common neurodegenerative disease after Alzheimer’s and affects around 170 000 people in France.

A neurologist at Pitié-Salpêtrière hospital in Paris and Inserm research director in Villejuif, Elbaz spent his childhood in Spain before moving to France in 1984 to begin his medical studies. It was at that point, when doing an internship in neurology, that it all clicked into place. ‘I was totally passionate about the discipline. The brain continues to remain very mysterious and we still have much to learn about how it works. And the field is also very vast with many sub-specialities, such as abnormal movements, multiple sclerosis and dementia,’ he describes. So he chose to do his residency in this field. But this was not enough – Elbaz decided to combine it with a degree in statistics. ‘I very quickly became interested in research, and particularly wanted to work on epidemiology in neurology,’ he explains. And so that became the subject of his thesis.

He then went on to specialise in Parkinson’s disease and began to receive patients suffering from abnormal movements at Paris’ Saint-Antoine hospital in 1998, followed by Pitié-Salpêtrière hospital from 2007. ‘I find this pathology particularly interesting because of the clinical dimension given to patient diagnosis and monitoring. The clinical examination is extremely refined in describing the manifestations of the disease, which vary widely from one person to another. And the interactions with the patients sealed the deal for me because of the same question that comes up again and again: Why am I suffering from this disease? What explanation can I give? From that point on, my goal was to give them answers.’

A duty to provide answers

Following a post-doc in the USA, Elbaz successfully passed the competitive examination to become an Inserm staff scientist in 2001, and then became research director in 2009. He began his work in the unit of Epidemiological Research in Neurology and Psychopathology, which was later renamed Neuroepidemiology. In 2012, he joined the Centre for Research in Epidemiology and Population Health in Villejuif, where he continues to work as a co-leader of the Exposome, Inheritance, Cancer and Health team. With over twenty years of research to his credit, the neurologist has already published major findings. For example, he established a link between exposure to pesticides and the risk of developing Parkinson’s disease in farmers. ‘This contributed to the recognition of this pathology as an occupational disease in the individuals concerned, entitling them to compensation. France pioneered this approach in 2012,’ he recalls. He established another link between place of residence and the risk of developing the disease (in french). ‘Using the National Health Data System (SNDS) database, and in partnership with Santé publique France, we showed that people living in highly agricultural areas, particularly winegrowing areas, are at higher risk than others,’ he explains.

Another source of data for his research is the E3N cohort (in french), an epidemiological study of women from France’s National Education System of which he is the scientific co-leader. ‘Around 100 000 women were enrolled in 1990 and have been monitored ever since, and with, more recently, the recruitment of their spouses, children and soon-to-be grandchildren. This very long follow-up is fundamental for us. It’s the only way to effectively search for risk factors preceding the onset of the disease, which is very progressive, with several years elapsing between the start of neurodegeneration and diagnosis,’ he clarifies. Thanks to this cohort, Elbaz has established a link between women’s physical activity level in mid-life and the subsequent reduction in Parkinson’s risk (in french). In parallel, he expanded his field of research in the past few years by studying motor performance during ageing in the general population and the factors likely to explain how they differ among individuals.

A prize and new perspectives

Recently, this rich career was crowned by the Éliane and Gérard-Pauthier Foundation Prize, under the aegis of Fondation de France. An invitation to pursue the new research in progress. ‘There is currently no preventive treatment. In our attempts to identify possible avenues, we’re analysing the SNDS database and E3N cohort for treatments taken in different indications that would be associated with a reduced risk of developing Parkinson’s later on. This would seem to be the case for some statins, used to treat high cholesterol,’ he explains. His team is also looking for epigenetic signatures that predict the risk of developing the disease. These chemical marks on DNA do not modify its sequence but alter gene expression and can be passed down through the generations.

‘The objective of all my research is prevention, summarises Elbaz. By identifying factors associated with the disease, I hope to contribute to the implementation of preventive measures to try to slow the expected increase in the number of cases. Between 2010 and 2030, due to population ageing, prevalence will increase by 60% and we’ll also have to manage more advanced and difficult-to-treat forms due to the longer life expectancy of patients. I’m hopeful that we’ll succeed, because the scientific community is undergoing a paradigm shift from a certain inevitability to a desire to prevent disease. In the US, for example, the Senate passed the National Plan to End Parkinson’s Act to develop prevention projects and improve treatment. Our research is part of this trend with, I hope, a tangible benefit for patients in the years to come,’ he concludes.