Effect of helminthic therapy on inflammaging, neuroinflammation and neurodegenerative diseases in mouse models
Pr Christophe Magnan
Université Paris Cité, CNRS UMR 8251
Google Scholar Christophe Magnan
Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies, Huntington’s disease, amyotrophic lateral sclerosis (also known as Charcot’s disease), frontotemporal dementia and Creutzfeldt-Jakob disease affect nearly 1.5 million people in France, or about 2% of the French population. Several studies show a link between inflammation, neuroinflammation and these diseases. Other studies of Amazonian hunter-gatherer populations, naturally exposed to intestinal worms (helminths), show one of the lowest rates of these diseases in the world (1), as well as a protective effect of helminths in individuals with a genetic predisposition to Alzheimer’s disease (2).
Chronic low-grade inflammation, which increases with age (“inflammaging”), is a key factor linking metabolic disorders (metabolic syndrome, obesity, type 2 diabetes) to neurodegenerative diseases. Innovative approaches to modulate the immune system are therefore needed. Helminthic therapy is based on the immunomodulatory properties of helminths, worms that have co-evolved with our species for millions of years. It represents a promising strategy that remains little explored in the context of neuroinflammation associated with metabolic disorders and the onset of neurodegenerative diseases.
This first project aims to assess, over 24 months, the effect of helminthic therapy on neuroinflammation and cognitive decline in standard and pathological mouse models. We will compare, over time, control mice with mice fed a high-calorie diet that induces obesity and diabetes, with or without exposure to helminths.
We will analyze brain inflammation in regions of interest involved in cognition and neurodegenerative diseases (hippocampus, cortex, olfactory bulb) using complementary approaches: histology and immunohistochemistry (microglial and astrocytic activation), in situ hybridization, single-cell transcriptomics (single-cell RNA-seq), and targeted molecular analyses. These approaches will allow us to characterize in detail the inflammatory signatures and the cell populations involved.
In parallel, we will assess the functional consequences through a battery of behavioral tests measuring memory (maze, object recognition) and olfactory function, the latter being an early marker of neurodegenerative diseases. Finally, we will collect tissues and plasma to build a biobank for future analyses (identification of biomarkers, active metabolites, etc.).
This program will provide essential mechanistic data on the immunomodulatory role of helminths along the gut-brain axis and could pave the way for new therapeutic strategies to prevent or slow neurodegenerative pathologies associated with metabolic disorders.
In addition, we also wish to measure the effect of helminths in animal models of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies, Huntington’s disease, frontotemporal dementia and amyotrophic lateral sclerosis. These projects will depend on the amount of funding obtained and on the relevance of the models.
The minimum funding required is €200,000 over 2 years, to cover the purchase and maintenance of animal models, omics and histological analyses, and behavioral tests. Additional funding will also make it possible to launch epidemiological and socio-medical studies and clinical studies in cooperation with other academic teams.
(1) Gatz M et al. Prevalence of dementia and mild cognitive impairment in indigenous Bolivian forager-horticulturalists. Alzheimers Dement. 2023 Jan;19(1):44-55. doi: 10.1002/alz.12626. Epub 2022 Mar 9. PMID: 35262289; PMCID: PMC9458772.
(2) Trumble BC et al. Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden. FASEB J. 2017 Apr;31(4):1508-1515. doi: 10.1096/fj.201601084R. Epub 2016 Dec 28. PMID: 28031319; PMCID: PMC5349792.
About the BFA
The Unit of Functional and Adaptive Biology (BFA, UMR 8251), directed by Prof. Christophe Magnan, is a joint research unit of Université Paris Cité and the CNRS. It is located on the Grands Moulins campus (Paris 13th arrondissement), within the Life Sciences Division of the Faculty of Sciences.
Recognized for its work in integrative biology, the unit studies the biological mechanisms by which the body adapts to environmental or internal disturbances (endocrine, metabolic, genetic), in both physiological and pathological contexts. Its research, which ranges from in silico to preclinical and clinical approaches, addresses major public health issues: the impact of the environment (nutrients, xenobiotics) on the emergence of type 2 diabetes, obesity, fertility disorders, neurodegenerative diseases and ageing. Bringing together bioinformaticians, chemists, biochemists, physiologists and clinicians within a single unit is a unique asset in the local and national scientific ecosystem.
The unit has around 150 people: about fifty permanent researchers, teacher-researchers and clinicians, 25 technical, engineering and administrative staff, as well as, each year, between 30 and 40 non-permanent staff (PhD students, postdoctoral researchers, contract staff) and about fifty trainees. It is organized into 7 teams, including one INSERM-affiliated team (ERL).