Détails de la réservation
- Le : 31 October 2019
- De : 14 h 00
- à : 15 h 00
- Salle : Amphi Broca Nouvelle - Aquitaine
Détails de l'évènement
Prof. Michael UGRUMOV
Institute of Developmental Biology RAS, Moscow, Russia
"Development of preclinical diagnosis of Parkinson’s disease – illusion or reality?"
Numerous attempts to develop a preclinical diagnosis of Parkinson's disease (PD) by searching biomarkers as prodromal premotor symptoms and changes in biological fluids (CSF, blood, etc.) are not fully successful. A drawback of this methodology is the search for biomarkers in body fluids in PD patients at the clinical stage without guarantees that they are characteristic for preclinical stage. Indeed, all biomarkers detected so far are non-specific. We propose to upgrade this methodology, using only markers found both in patients and animals at modeling clinical (symptomatic) and preclinical (presymptomatic) stages of PD. Detection of the same marker in patients and symptomatic animals is believed to indicate adequate reproduction of pathogenesis along this metabolic pathway, and detection of this marker in presymptomatic animals proves its specificity for preclinical stage. We showed that 50% and 20% of the markers found in blood of patients were characteristic of MPTP-treated symptomatic and presymptomatic mice, respectively. Besides, we propose a fundamentally different approach to early diagnosis of PD - a provocative test that has been successfully used for decades in internal medicine. We showed that the systemic administration of α-methyl-p-tyrosine, a reversible inhibitor of dopamine synthesis (provocative agent), to MPTP-treated mice at presymptomatic stage results in a reversible decrease in dopamine level in the striatum up to the threshold (30%), followed by short-term motor disorders. In controls, although the dopamine level decreases under α-methyl-p-tyrosine administration, it does not reach the threshold level and, therefore, is not accompanied by motor disorders. Thus, we developed a new complex methodology for the development of preclinical diagnosis of PD.
- Nom : Erwan Bezard