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Conference by Adrien Meguerditchian

Published on March 28, 2017



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 Transversal projects 

Cell replacement therapy for early Parkinsonís disease

 

The transversal project of the Stem-cell and Brain Research Institute aims at evaluating the efficiency of early cell grafting in the early stages in a pre-clinical model of Parkinson’s disease. The project is implemented using precise motor, cognitive, and circadian assessments of the early stages of the disease, as well as the derivation and characterisation of appropriately defined cell lines for grafting.

Behavioural dysfunctions in Parkinson’s disease are initiated during the so-called presymptomatic period (i.e. before clinical characterisation). The compensatory mechanisms and potentially hidden deficits that characterize this early period remain largely unknown. Yet during this period the brain is undergoing major changes as a direct consequence of the progressive dopaminergic lesion and as a consequence of compensations.

One hypothesis is that early action on the disease will improve the efficacy of replacement therapy. Cell therapy is one major alternative to overcome the dopamine cell loss observed in Parkinson’s disease. Several tests have been made in animals and humans and the outcome appears to depend on at least three major parameters: i) the nature/specificity of the cells that are transplanted, ii) the site of grafting, and iii) the stage of the disease or the level of dopaminergic alteration at the time of grafting.

The transversal project involves all five teams of the institute:

  • The genetic derivation of labeled ES cell lines for preclinical cell therapy in neurodegenerative diseases (Savatier/Dehay)
  • The generation of astrocytes from ES cells to be co-grafted with dopaminergic precursors in the striatum and SN of parkinsonian models (Dehay)
  • The identification of neurodegenerative processes (Procyk/Kennedy Leviel)
  • The behavioural and neurophysiological correlates of the consequences of slow evolving lesions on executive functions (Procyk)
  • The evaluation of chronobiological markers during neurodegeneration using chronic neurophysiology and continuous multi-dimensional behaviour monitoring (Cooper)


  • Dr. Howard Cooper

    The research aims of Neurobiological Rhythms and Sleep are focused on the molecular, cellular and behavioral mechanisms of the circadian timing system and the consequences of aging and neurodegenerative disease.Our approaches strive to understand the mechanisms of synchronization of circadian rhythms by lignt, the molecular and physiological mechanisms of the endogenous circadian oscillators, and the regulation of output behavioral and physiological rhythms. The coding of photic information ...

    Colette Dehay

    Team leader


    Henry Kennedy

    SBRI investigates the development, function and repair of neuronal circuits involved in cognition, motor control and biological rhythms and researches the structural foundations of computation in the cortex. We seek to develop embryonic stem cell based therapies so as to reverse the effects of brain lesions leading to the motor and cognitive deficits found in neurological disease including Parkinson's.


    Florence Wianny

    My research interests include neural stem cells derived from Embryonic Stem cells in the non-human primate, the study of their self-renewal, and their differential potential.


    Selected Publications of Team members :
    Fifel K, Vezoli J, Dzahini K, Claustrat B, Leviel V, Kennedy H, Procyk E, Dkhissi-Benyahya O, Gronfier C, Cooper HM (2014) Alteration of daily and circadian rhytms following dopamine depletion in MPTP treated Non-Human Primates. PLoS One, 2014, 9(1):e86240
    Vezoli J, Dzahini K, Costes N, Wilson CR, Fifel K, Cooper HM, Kennedy H, Procyk E (2014) Increased DAT binding in the early stage of the dopaminergic lesion: a longitudinal [11C]PE2I binding study in the MPTP-monkey. Neuroimage 102:249-261
    Vezoli J, Fifel K, Leviel V, Dehay C, Kennedy H, Cooper HM, Gronfier C, Procyk E (2011) Early Presymptomatic and Long-Term Changes of Rest Activity Cycles and Cognitive Behavior in a MPTP-Monkey Model of Parkinsonís Disease. PLoS One, 2011, 6(8):e23952 download