Profile : A master degree in neuroscience with high rating is requested.
Project : Parkinson’s disease (PD) is a neurodegenerative disease that affects about 200,000 people in France. Due to the ageing of the population and the improvement in life expectancy, the incidence of the disease is increasing. PD is related to the loss of dopaminergic neurons (DA) from Substantia Nigra associated with abnormal alpha-synuclein deposits. One of the experimental therapeutic approaches in this pathology consists in grafting DA neurons from the fetal ventral mesencephalon to the striatum. In Parkinson’s patients, clinical trials of intrastriatal transplantation of DA neurons have led to some clinical improvements but have not yet reached a level that would justify the routine use of this approach. This is mainly due to 1) the limited number of cells to be transplanted, as well as difficult standardization and ethical problems in the use of human fetal neurons, 2) limited therapeutic efficacy, partly related to the ectopic position of the grafts. In some patients, after autopsy, 10 to 22 years after transplantation, some of transplanted neurons contained aggregates of α -synuclein, similar to those observed in the host brain. Our hypothesis is that the ectopic site of the graft exposes the transplanted neurons to a microenvironment that is not favorable (deficit in neurotrophic factors, absence of specific innervations) making them more vulnerable to the pathological process such as the transfer of α-synuclein from the host to the graft. In this project, we propose to study the possibility of transporting the aggregates of α-synuclein from the host to the new dopaminergic neurons grafted either homotopically (at the level of substantia nigra) or ectopically (at the level of striatum).
Application : Please send CV and 2 references to Pr. Afsaneh Gaillard (Afsaneh.firstname.lastname@example.org)
Deadline : 12th of April