PREPARK

BACKGROUND

Parkinson's disease (PD) is an incurable neurodegenerative disorder that progresses silently for decades. By the time it becomes clinically visible, notably through the onset of characteristic motor symptoms (akinesia, rigidity, resting tremors), brain damage is already irreversible. Approximately 70% of dopaminergic neurons in the substantia nigra pars compacta are destroyed by this stage, rendering any attempts at curative treatment or even slowing down degeneration ineffective. Furthermore, current diagnostic methods lack reliability in the early stages, with confirmation often delayed by several years after the appearance of motor symptoms. This diagnostic odyssey is compounded by a lack of specificity regarding other Parkinsonian syndromes.

To address these limitations, the GIN has established an approach combining animal models and newly diagnosed (de novo) patient cohorts. This strategy led to the discovery and patenting of a blood biomarker composed of six metabolites (pyruvate, valine, creatine, betaine, acetoacetate, and β-hydroxybutyrate). This biomarker distinguishes de novo Parkinsonian patients from healthy subjects with an 83% accuracy and also anticipates the disease in animals during the prodromal phase (patent FR2011817; Mallet et al., 2022). The current objective is to advance this biomarker toward clinical application by validating its specificity and early detection capability.

GOING FURTHER WITH THE SUPPORT OF LabEx CerCoG

Two major directions are now being pursued to confirm the clinical value of the identified biomarker. The first, the specificity axis, aims to determine whether this biomarker is specific to PD or if it is present in other neurodegenerative diseases. Analyses will be performed on 120 blood samples from patients with Alzheimer's disease, multiple system atrophy (MSA), and progressive supranuclear palsy (PSP), utilizing a NIH biobank.

The second, the early-detection axis, evaluates the biomarker's ability to detect the disease at a prodromal stage. To this end, samples from the ICEBERG cohort (Prof. M. Vidailhet), collected over five years from patients with rapid eye movement sleep behavior disorder (an early indicator of PD with an 80% phenoconversion rate), will be analyzed. This work will cover 450 samples, including healthy individuals and patients who have progressed to PD.

Metabolomic analyses will be carried out on the IRMaGe platform using nuclear magnetic resonance, following the protocol already validated in previous studies. Operational funding is secured, but support is needed to strengthen human resources. LabEx CerCoG funding would allow the recruitment of a research engineer for 2.5 months to perform the analyses, process, and exploit the data. The contract is scheduled to start on September 1, 2025, to ensure optimal access to the platform.

This support represents a decisive step in advancing this interdisciplinary project at the interface of chemistry and diagnostic medicine. It will help move toward clinical application of the biomarker by consolidating its specificity and early detection capability, and will contribute to the valorization of the research initiated with SATT Linksium, which is currently in the pre-maturation phase.