Team “Gene Therapy” - Institut du Cerveau

Scientific Teams

Team “Gene Therapy”

Presentation

Gene therapy Main domain: Clinical & translational neurosciences Subdomain : Molecular & cellular neuroscience Nathalie CARTIER’s team develops gene therapy strategies for severe neurodegenerative diseases including Huntington's disease, Spinocerebellar ataxias, Alzheimer's disease and genetic leukodystrophies. Research includes proof of concept in animal models and translational steps to clinical applications. The team aims to propose a phase I/II therapeutic trial in 2020 for Huntington disease. The team will also develop tools for the delivery of therapeutic molecules in the brain (use of microglia, optimization of AAV for intravenous administration, optogenerapy for time-controlled delivery).

Major publications

Nóbrega C, Mendonça L, Marcelo A, Lamazière A, Tomé S, Despres G, Matos CA, Mechmet F, Langui D, den Dunnen W, de Almeida LP, Cartier N, Alves S. Restoring brain cholesterol turnover improves autophagy and has therapeutic potential in mouse models of spinocerebellar ataxia. Acta Neuropathol. 2019 Nov;138(5):837-858.
Boussicault L.*, Alves S.*, Lamazière A., Planques A., Heck N., Moumné L., Despres G., Bolte S., -Hue A., Pagès C., Galvan L., Piguet F., Aubourg P., Cartier N.*, Caboche J.* and Betuing S.*. Cyp46-A1, the rate-limiting enzyme for cholesterol degradation, is neuroprotective in Huntington’s Disease. Brain 2016 Mar;139(Pt 3):953-70.
Fol R., Braudeau J., Ludewig S., Abel T., Weyer S.W., Roederer J.P., Brod F., Audrain M, Bemelmans A.P., Buchholz C.J., Korte M., Cartier N.*#, Müller U.C.*#. Viral gene transfer of APPs rescues synaptic failure in an Alzheimers disease mouse model. Acta Neuropathol. 2015 Nov 4.
Burlot M.A., Braudeau J., Michaelsen-Preusse K., Potier B., Ayciriex S., Varin J, Gautier B., Djelti F., Audrain M., Dauphinot L., Fernandez-Gomez F.J., Laprévote O., Bièche I., Auzeil N., Potier M.C., Dutar P., Korte M., Buée L., Blum D., Cartier N. Cholesterol24-hydroxylase defect is implicated in memory impairments of Alzheimer-like Tau pathology. Hum Mol Genet. 2015: 24: 5965-76.
Djelti F., Braudeau J., Hudry E., Dhenain M., Varin J., Bièche I., Marquer C., Chali F., S Ayciriex, Auzeil N., Alves S., Langui D., Potier M.C., Laprevote O., Vidaud M., Duyckaerts C., Miles R., Aubourg P.*, Cartier N.* Cholesterol-24-hydroxylase (CYP46a1) inhibition and accumulation of neuronal cholesterol in hippocampus leads to amyloid production, neurodegeneration and paves the way for Alzheimer’s disease. Brain 2015: 138: 2383-98.