Prion diseases are rare, progressive, and incurable neurological disorders that naturally afflict both humans and animals, with the former including Creutzfeldt−Jakob disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS), and fatal familial insomnia (FFI).
Decades of research have determined that these disorders share a common molecular mechanism: the conversion of the cellular prion protein (PrPC) into an infectious form (PrP scrapie, PrPSc) that accumulates in the brain affected individuals. Notably, a great deal of evidence suggests that PrPC has a critical role in supporting PrPSc propagation and transducing its neurotoxicity.
For the past five years, we have employed a previously developed highly robust and quick assay to search for compounds capable of suppressing PrPC-mediated toxicity. Thanks to this method, called drug-based cell assay (DBCA), we developed a class of drug-like molecules capable of counteracting prion toxicity. In particular, the most promising derivative (Mol101) showed potent activity in cell and mouse brain slice models of prion diseases.
In light of these promising results, our project aims at evaluating the therapeutic efficacy of Mol101 in a new mouse model for inherited CJD. Our study will be instrumental in reaching a reliable conclusion regarding the possible translation of these therapeutics in prion disease patients.
About the Researcher:
Maria Letizia Barreca, PhD
Department of Pharmaceutical Sciences (DPS), University of Perugia-Italy
Prof. Barreca has 20+ years of experience in the field of medicinal chemistry and rational drug discovery, with particular expertise in infectious diseases, including prion diseases.
She started her carrier at the University of Messina (Italy), where she founded a research laboratory in the field of computational chemistry applied to drug discovery. In 2000-2001, Prof. Barreca was Visiting Scientist at the University of Houston (Texas, USA), and in 2007 she moved to the Department of Pharmaceutical Sciences at the University of Perugia (Italy), where she set up the I2D Lab (In silico Drug Discovery Laboratory) and is now Associate Professor.
Prof. Barreca has successfully collaborated on several multidisciplinary projects focused on the rational identification and development of bioactive small molecules.
She is author of 97 papers, and co-inventor of 3 patents relating to novel pharmacological agents for neurodegenerative diseases.
Prof. Barreca has received awards and acknowledgments for her scientific activity, including the "Farmindustria Prize for Pharmaceutical Research".
She is a member of the Editorial Advisory Board for ACS Medicinal Chemistry Letters and co-founder of the innovative Start-up Sibylla Biotech S.R.L (www.sibyllabiotech.it).
- The Fred Glavan/Lee Gallagher Family Memorial Grant, contributed by the Glavan and Gallagher Families
- The Robert Dodd Memorial Research Grant, contributed by Kathleen Dodd and Family
- The Chuck Fear Memorial Research Grant, contributed by Pamela Fear and Family
- The Linda L. Sullivan Memorial Grant, contributed by the Sullivan Family
- The Donna Tepe Memorial Grant, contributed by Jeff Tepe and Family