Venue : Centre Broca Nouvelle-Aquitaine
“Development of preclinical diagnosis of neurodegenerative diseases – illusion or reality?”
Prof. Michael UGRUMOV
Institute of Developmental Biology of Russian Academy of Sciences,
Moscow, Russia
Abstract
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.
Professor Michael Ugrumov,
MD, PhD, Head of Laboratory of Neural and Neuroendocrine Regulations at the Institute of Developmental Biology of Russian Academy of Sciences (RAS),
Professor of Department of Psychology at the National Research University “Higher School of Economics” (Moscow),
Vice-President of the Russian Society for Physiology,
President of the Russian Society for Neurochemistry, former adviser to the President of RAS and the Ministry of Education and Science of RF , coordinator of the program of the Presidium of RAS on Brain Research.
Ugrumov graduated from the University Medical School (Moscow), got PhD at the Institute of Evolutionary Physiology and Biochemistry RAS (St. Petersburg) and Professorship at the Institute of Developmental Biology and the University Medical School (Moscow). Ugrumov is a member of RAS, European Academy of Science and Arts, Serbian Academy of Sciences and Arts, French National Academy of Pharmacy and nominated as a visiting Professor at Tokushima University Medical School (Japan), SUNY Upstate Medical University (Syracuse, USA), University P. et M. Curie (Paris, France), University Medical School of Ulm (Germany). Ugrumov was awarded the Prize of the American Society of Experimental Biologists, the Order of Merit for France, the Orbeli Prize and Sechenov Prize of RAS.
Main interests: Developmental Neurobiology, Neuroendocrinology, Neurodegenerative Diseases.