Benjamin Dehay lauréat d’un ANR PRCI

Benjamin Dehay (IMN) has been awarded, as coordinator, PRCI 2025 funding from the ANR (Axis C.10 – Biomedical Innovation – CE18) for the project ‘TreatPD – An RNA to treat Parkinson’s disease’.

Involved researchers and laboratories

• Benjamin Dehay, French coordinator (IMN – UMR5293 CNRS, Univ. Bordeaux)
• Chantal Pichon, French partner (ART-ARNm – UMS55 Inserm, Univ. Orléans)
• Philippe Barthélémy, French partner (ARNA – U1212 Inserm, UMR 5320 CNRS, Univ. Bordeaux)
• Yvan Devaux, Luxembourgish coordinator (Luxembourg Institute of Health (LIH))

Project Summary and Impact

Parkinson’s disease (PD) is an age-related, progressive, neurodegenerative disease that is complex, heterogeneous, and deadly. The main symptoms are movement disorders (tremors and muscle rigidity), which affect patients daily. PD specifically affects the central nervous system and is characterized by a loss of dopamine production in the brain. Consequently, due to population ageing, the prevalence of PD is increasing and is associated with a high socio-economic burden. Actual therapy for PD targeting the restoration of dopamine levels can effectively relieve symptoms. However, it does not treat the disease’s root cause and cannot prevent its progression. PD is, therefore, still considered irreversible and incurable. Hence, there is an unmet clinical need for disease-modifying therapies for PD.

We identified an RNA molecule, arbitrarily named lncG1, that is dysregulated in PD patients. Our preliminary experiments show that lncG1 overexpression in cultured neurons stimulates the dopamine synthesis pathway and increases dopamine production. Based on these supporting data, we hypothesize that lncG1 may be used as a PD-modifying therapy. In the present project, we aim to develop a novel nanoparticle carrier of lncG1 that can cross the blood-brain barrier and target dopaminergic neurons in the brain.

The project involves five scientific tasks and three non-scientific tasks. Specifically, ART-ARNm will produce a synthetic lncG1. LnG1 will then be embedded into the carrier of nucleolipid nanoparticles by the ARNA lab to ensure its capacity to cross the blood-brain barrier and release into dopaminergic neurons. This carrier, NP-lncG1, will be tested in murine models of PD by IMN to check in vivo its capacity to cross the blood-brain barrier and to evaluate its effect on dopaminergic neurons. These murine models will also allow the investigation of different administration routes and the tissue distribution of exogenously administered lncG1.

The impacts of this project are as follows: a) Societal impact: reduce psychological impact by bringing hope to PD patients, their families, and caregivers by developing a novel clinically applicable disease-modifying therapy, reducing symptoms, and improving quality of life and life expectancy; b) Economic impact: reduction of healthcare costs through a modification of the disease trajectory; c) Scientific impact: increased knowledge of the role of RNA molecules in PD development. To ensure these impacts are reached and end-users accept the solution provided by this project, the main stakeholders (neurologists, patients) are involved in the project at an early stage. They will greatly participate in the dissemination and adoption of project results.

Relevance of the partnership

Complementary expertise from four partners, three in France and one in Luxembourg, is necessary to develop and test the nanocarrier. Thus, the TreatPD project builds upon the expertise of French partners in RNA production (Technology research accelerator ARM messager, ART-ARNm, INSERM Paris), nanoparticles (Nucleic acid, natural and artificial regulation, ARNA, Bordeaux University), and in vivo models of PD (Institute of neurodegenerative diseases, IMN, Bordeaux University), with a Luxembourgish partner with expertise in RNA and has identified lncG1 (Luxembourg Institute of Health, LIH). In parallel, LIH will develop in silico and in vitro investigations to fully characterize the molecular mechanism of action of lncG1, validate its capacity to stimulate the dopamine synthesis pathway, and identify potential side effects. Through a partnership with a spin-off of the University of Luxembourg, LIH will further investigate the effects of NP-lncG1 in human brain organoids, including dopaminergic neuron survival, dopamine production, and other pathways identified during this project. Overall, the work plan beyond the TreatPD project is designed to develop and extensively validate NPlncG1, a nanoparticle carrier of neuroprotective lncG1.