*THÉRÈSE DI PAOLO

Catecholamine-Regulated Protein 40 (CRP40) as a New Candidate Biomarker for Early Diagnosis of Parkinson’s Disease

Challenge: Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder afflicting 1 to 2% of the population over 65 years of age and for which there is neither a reliable diagnostic test nor cure. Since catecholamine-regulated protein 40 (CRP40) may be involved in regulation of dopamine in the brain, it represents a potential biomarker for early diagnosis of Parkinson’s disease. However, it requires validation in preclinical animal models and in human subjects.

Solution: The goal of this project was to validate if CRP40 expression represents a biomarker for early diagnosis of PD. The team designed assays to analyze CRP40 mRNA (RT-PCR) and protein expression (ELISA) in the blood of PD patients. The investigators also measured drug treatment effects with l-DOPA (the gold standard treatment for PD) and pramipexole (an agonist of dopamine) in Parkinsonian monkeys and in blood of patients affected by the disease. Longitudinal studies on PD patients and different groups of controls (healthy individuals or suffering from other neurodegenerative diseases) were performed in Quebec and Ontario.

Achievements/Impact: Thirty patients were successfully recruited for each of PD, dementia, stroke, respectively. Thirty newly diagnosed, drug-naïve PD patients and age and gender matched healthy controls were also recruited in each province. Unfortunately, CRP40 mRNA level measurements were inconsistent and sometimes too low to be measured in some patients and controls. In contrast, the ELISA assay could detect CRP40 protein expression in human platelets. Although the assay could differentiate healthy individuals (higher CRP40 levels) from sick patients, it could not distinguish specific pathologies since all PD patients, stroke victims and Alzheimer’s disease patients showed reduced CRP40 protein levels. More work is thus necessary to support the diagnostic utility of the test in a clinical environment.

Principal Investigators:

Thérèse Di Paolo
Université Laval

Ram Mishra
McMaster University

Co-investigators

Joseph Gabriele
CRP40 Inc/Ontario

Pierre Blanchet
Centre hospitalier de l’Université de Montréal

Completed Project
$750,000 / 3 years
Supported by CQDM through:
• AstraZeneca
• Merck
• Pfizer
• MESI
• RCE-E