DERREUMAUX Philippert
LBT Paris
France
A new Generation of Drugs for ALzheimers disease based on in vitro and in silico experiments of beta-amyloid oligomers and in vivo tests
ANR
584,927
01/01/2013
4.0
Alzheimer's disease & other dementias
GRAL: Generation of efficient drugs against Alzheimer’s disease
Alzheimer’s disease is affecting more than 24 million people worlwide and represents a 1000 billion dollars cost to our society. Thus far, no disease-modifying treatments exist.
A scientific challenge: determination of the first 3D structures of the amyloid-beta protein complexed by inhibitors to discover efficient drugs
The GRAL project, which integrates different and complementary expertises from chemistry, biophysics, structural biology, computer simulations, in silico design and screening of compounds to transgenic flies and mice, aims at discovering efficient therapeitic agents against Alzheimer’s disease.
State of the art in vitro, in silico and in vivo methods
Low-resolution experimental methods used: DLS, SEC, AUC, TEM, ESI-MI, Spectroscopies (CD, FTIR, Fluorescence).
Insights into atomic information from NMR, and spin labels followed by EPR.
Multi-scale computer simulations (all-atom, coarse grained OPEP)
Discovery of very efficient drugs validated by tests on transgenic flies and mice.