PREPARK

BACKGROUND

Parkinson's disease (PD) is an incurable neurodegenerative disorder that progresses silently for decades. By the time it becomes clinically apparent—notably through the onset of characteristic motor symptoms (akinesia, rigidity, resting tremors)—brain damage is already irreversible. By this point, approximately 70% of the dopaminergic neurons in the substantia nigra pars compacta have been destroyed, rendering any attempt at a curative treatment or even slowing the degeneration ineffective. Furthermore, current diagnostic methods lack reliability in the early stages, with confirmation often delayed by several years after the onset of motor symptoms. This diagnostic uncertainty is exacerbated by the lack of specificity compared to other parkinsonian syndromes.

In light of these limitations, the GIN has implemented an approach combining animal models and cohorts of newly diagnosed (de novo) patients. This strategy has led to the discovery and filing of a patent for a blood biomarker composed of six metabolites (pyruvate, valine, creatine, betaine, acetoacetate, and β-hydroxybutyrate). This biomarker can distinguish de novo Parkinson’s patients from healthy subjects with 83% accuracy and also predicts the disease in animals during the prodromal phase (patent FR2011817; Mallet et al., 2022). The current goal is to advance this biomarker toward clinical application by validating its specificity and early detection capability.

GOING THE EXTRA MILE WITH THE SUPPORT OF LABEX CerCoG

Two major lines of research are now underway to confirm the clinical value of the identified biomarker. The first, the specificity study, aims to determine whether this biomarker is specific to PD or whether it is also found in other neurodegenerative diseases. Analyses will be conducted on 120 blood samples from patients with Alzheimer’s disease, multiple system atrophy (MSA), and progressive supranuclear palsy (PSP), using a biobank from the NIH.

The second, the early detection axis, assesses 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 REM sleep disorders (an early indicator of PD with an 80% rate of phenoconversion), will be analyzed. This study will involve 450 samples, including healthy individuals and patients who have progressed to PD.

Metabolomic analyses will be conducted on the IRMaGe platform using nuclear magnetic resonance, following the protocol already validated in previous studies. Funding for operations is secured, but support is needed to strengthen human resources. Funding from LabEx CerCoG the recruitment of a research engineer for 2.5 months to perform the analyses and process and interpret the data. The contract is scheduled to begin on September 1, 2025, to ensure optimal access to the platform.

This support represents a decisive step forward for this interdisciplinary project at the intersection of chemistry and diagnostic medicine. It will enable progress toward the clinical application of the biomarker by strengthening its specificity and early detection capabilities, and will contribute to the commercialization of the research initiated with the spin-off company Linksium, which is currently in the pre-maturation phase.