Pixantrone (BBR2778) reduces the severity of experimental allergic encephalomyelitis.
Pixantrone is less cardiotoxic and is similarly effective to mitoxantrone (MTX) as an antineoplastic drug. In our study, pixantrone reduced the severity of acute and decreased the relapse rate of chronic relapsing experimental allergic encephalomyelitis (EAE) in rats. A marked and long-lasting decrease in CD3+, CD4+, CD8+ and CD45RA+ blood cells and reduced anti-MBP titers were observed with both pixantrone and MTX. In vitro mitogen- and antigen-induced T-cell proliferation tests of human and rodents cells evidenced that pixantrone was effective at concentrations which can be effectively obtained after i.v. administration in humans. Cardiotoxicity was present only in MTX-treated rats. The effectiveness and the favorable safety profile makes pixantrone a most promising immunosuppressant agent for clinical use in multiple sclerosis (MS).
Cavaletti
G
G
Department of Neuroscience and Biomedical Technologies, University of Milan Bicocca, and Department of Neurology, S. Gerardo Hospital, Monza, Italy. guido.cavaletti@unimib.it
Cavalletti
E
E
Crippa
L
L
Di Luccio
E
E
Oggioni
N
N
Mazzanti
B
B
Biagioli
T
T
Sala
F
F
Sala
V
V
Frigo
M
M
Rota
S
S
Tagliabue
E
E
Stanzani
L
L
Galbiati
S
S
Rigolio
R
R
Zoia
C
C
Tredici
G
G
Perseghin
P
P
Dassi
M
M
Riccio
P
P
Lolli
F
F
D000208:Acute Disease; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002908:Chronic Disease; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007546:Isoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D018655:Lymphocyte Count; D008942:Mitoxantrone / Q000009:adverse effects / Q000627:therapeutic use; D051381:Rats; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D007166:Immunosuppressive Agents; D007546:Isoquinolines; D008942:Mitoxantrone; C086548:pixantrone