PI: Cristina Agresti and Marco Salvetti
INSTITUTE Italian National Institute of Health
ADDRESS Viale Regina Elena n. 299, Roma
Agresti, Salvetti, Abbracchio, Eberini and Olla represent the Italian groups involved in the drug discovery. Salvettiat ats Sant’ Andrea Hospital has a long lasting expertise in development of new therapies for neurodegenerative diseases, thanks to drug repurposing approach and no-profit phase II clinical trials. DiSFeB at UNIMI (Eberini) is a leading research structure in Italy, with over 100 publications/year and a documented expertise in the mechanism of action, pharmacology and toxicology of drugs, and in the set up of new therapies, with a strong focus on neurodegenerative diseases. The Department of Cell Biology and Neuroscience at ISS (Agresti, Olla) has been engaged in research on nervous system disorders and MS for many years. The Institute of genetics and biomedical research at IRGB-CNR (Olla) supports Drug Discovery and Development projects in screen to hit, hit to lead and lead optimization phases by applying structure and ligand based drug design, molecular dynamics, QSPR (quantitative structure pharmacokinetic relationship) and ADME-Toxicological optimization.
The Study design take advantage of the collaboration of: i) Salvetti’s group, who has pioneered and pursued the repurposing approach in MS and other neurological diseases and has experience in large database creation and management, including data on gene-target interactions and relevance assessment; ii) Abbracchio’s group at DiSFeB, who has expertise in the stem cell properties of glial cells after CNS damage and on the development of neuro-regenerative therapies. Work of the group unveiling GPR17 as an OPC regulator has lead the National Multiple Sclerosis Society USA to propose GPR17 as a Model Receptor for novel remyelinating therapies. The group has proposed the repurposing of the drug montelukast in CNS disorders characterized by cognitive decline; iii) Ivano Eberini’ group at DiSFeB, with long-standing expertise in computational biochemistry and system biology applied to the dynamic behaviour of proteins and to the interaction of drugs/xenobiotics with macromolecules. This group routinely applies in silico approaches for predicting ADME parameters, computing kinetic constants, identifying physically significant descriptors and pharmaceutical properties, and uses QSAR models to estimate ADME; iv) Agresti’s group, with long lasting expertise in OPCs in CNS pathophysiology, transcriptome and protein-protein interaction analysis. The Group has validated a multiple-step in vitro/ex vivo screening assay on rodent OPC/cerebellar slices to discover novel drug candidates for diseases with poorly understood pathophysiology. This group collaborates with v) Stefania Olla at IRGB-CNR, a computational chemist with industrial and academic expertise in supporting drug discovery via virtual screening technologies and optimization of compounds through molecular modeling approaches.
lysolecithin-demyelinated cerebellar slices