title: Monitoring disease evolution and treatment response in lysosomal disorders by the peripheral benzodiazepine receptor ligand PK11195.
abstract: Microglia activation and neuroinflammation play a pivotal role in the pathogenesis of lysosomal storage disorders (LSD) affecting the central nervous system (CNS), which are amenable to treatment by hematopoietic stem cell transplantation (HSCT). HSCT efficacy relies on replacing the intra- and extra-vascular hematopoietic cell compartments, including CNS microglia, with a cell population expressing the functional enzyme. Non-invasive and quantitative assessment of microglia activation and of its reduction upon HSCT might allow for evaluation of disease evolution and response to treatment in LSD. We here demonstrate that microglia activation can be quantified ex vivo and in vivo by PET using the peripheral benzodiazepine receptor ligand PK11195 in two models of LSD. Furthermore, we show a differential PBR binding following microglia replacement by donor cells in mice undergoing HSCT. Our data indicates that PBR ligands constitute valuable tools for monitoring the evolution and the response to treatment of LSD with CNS involvement, and enable us to evaluate whether the turnover between endogenous and donor microglia following HSCT could be adequate enough to delay disease progression.
authors.affiliation: San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Visigalli
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Moresco
authors.forename: Sara
authors.initials: S
authors.lastname: Belloli
authors.forename: Letterio S
authors.initials: LS
authors.lastname: Politi
authors.forename: Angela
authors.initials: A
authors.lastname: Gritti
authors.forename: Daniela
authors.initials: D
authors.lastname: Ungaro
authors.forename: Mario
authors.initials: M
authors.lastname: Matarrese
authors.forename: Elia
authors.initials: E
authors.lastname: Turolla
authors.forename: Andrea
authors.initials: A
authors.lastname: Falini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Scotti
authors.forename: Luigi
authors.initials: L
authors.lastname: Naldini
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Fazio
authors.forename: Alessandra
authors.initials: A
authors.lastname: Biffi