title: Differential targeting of immune-cells by Pixantrone in experimental myasthenia gravis.
abstract: Pixantrone was shown to reduce the severity of clinical manifestation in experimental myasthenia gravis. In the present work we further studied its therapeutic effect. Our results demonstrate that a single administration suppressed AChR-specific immune-responses in primed rats. However, clinical symptoms could be improved only by repeated drug administrations (q7dx6 protocol-8.12 mg/kg); this treatment allowed stable serum drug levels for at least 7 days, as assessed by a functional T-cell bioassay. Pixantrone exerted strong in vitro inhibitory effect only on proliferating T-cells without impairing dendritic cell differentiation and B-cell viability. Our data further demonstrate that Pixantrone is a promising immunosuppressant drug that should be investigated in myasthenia gravis.
authors.affiliation: Preclinical Neuroimmunology Laboratory, Neurology IV, Neurological Institute Carlo Besta, Milan, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Marolda
authors.forename: Chiara
authors.initials: C
authors.lastname: Ruocco
authors.forename: Chiara
authors.initials: C
authors.lastname: Cordiglieri
authors.forename: Chiara
authors.initials: C
authors.lastname: Toscani
authors.forename: Carlo
authors.initials: C
authors.lastname: Antozzi
authors.forename: Renato
authors.initials: R
authors.lastname: Mantegazza
authors.forename: Fulvio
authors.initials: F
authors.lastname: Baggi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D007546:Isoquinolines / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology*; D023461:Myeloid Progenitor Cells / Q000187:drug effects / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D060888:Real-Time Polymerase Chain Reaction; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology*
chemical_list: D007546:Isoquinolines; D059005:Topoisomerase II Inhibitors; C086548:pixantrone