Numerous data in animal models and in human patients have shown the role of impaired cholesterol metabolism in neurodegenerative diseases, particularly in Huntington’s disease (HD) and Alzheimer's disease (AD).
CYP46A1 - a key enzyme that eliminates brain cholesterol in excess - is reduced in the brain of patients and mice models of these conditions. Through eliminating the excess of cholesterol, CYP46A1 activates the cholesterol biosynthesis pathway, whose intermediates compounds play major roles in fundamental processes such as intracellular transport, signaling and memory.
Our therapeutic strategy is to overexpress CYP46A1 in the regions of the brain affected by the disease through neuronal transduction with an Adeno Associated Virus (AAV) vector carrying the CYP46A1 gene.
This strategy allows us to restore cerebral cholesterol metabolism in the brain and slow down the progression of these diseases.
We evidenced in several mice model of HD and AD that overexpressing CYP46A1 corrects the disease.
We plan to be first in man in 2020 for HD and in 2021 for AD.
Brainvectis founder and CSO - Dr Nathalie Cartier-Lacave - has a deep knowledge of gene therapy to treat severe neurodegenerative diseases. Nathalie is principal investigator in two clinical trials using gene therapy to treat children affected by leukodystrophies (ALD, MLD).