Monitoring disease evolution and treatment response in lysosomal disorders by the peripheral benzodiazepine receptor ligand PK11195

Ilaria Visigalli, Rosa Maria Moresco, Sara Belloli, Letterio S. Politi, Angela Gritti, Daniela Ungaro, Mario Matarrese, Elia Turolla, Andrea Falini, Giuseppe Scotti, Luigi Naldini, Ferruccio Fazio, Alessandra Biffi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)51-62
Number of pages12
JournalNeurobiology of Disease
Volume34
Issue number1
DOIs
Publication statusPublished - Apr 2009

Keywords

  • Hematopoietic stem cell transplantation
  • Lysosomal storage disorders
  • Microglia
  • Neuroinflammation
  • Peripheral benzodiazepine receptor ligands
  • Positron emission tomography

ASJC Scopus subject areas

  • Neurology

Fingerprint Dive into the research topics of 'Monitoring disease evolution and treatment response in lysosomal disorders by the peripheral benzodiazepine receptor ligand PK11195'. Together they form a unique fingerprint.

  • Cite this