Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitoxantrone is one of the few FDA-approved drugs available to treat rapidly progressing forms of multiple sclerosis; however, its utilization is compromised by a cardiotoxic potential and the risk of mitoxantrone-induced leukemia. BBR3378, a novel aza-anthrapyrazole, is structurally similar to mitoxantrone, but lacks the ring hydroxyls that may contribute to cardiotoxicity. Here, we investigated the therapeutic activity of BBR3378 in a C57BL/6 mouse model of multiple sclerosis. Mice given BBR3378, before or after the priming and expansion of MOG-specific responses, were protected from ascending paralysis. Strikingly, two doses of BBR3378 given a week after EAE induction were sufficient to provide significant protection from clinical symptoms and reduce MOG-specific proinflammatory T cell cytokine production, and serum IgG responses. Furthermore, while mitoxantrone is associated with persistent lymphopenia and cardiotoxicity, no such outcomes were detected in BBR3378-treated mice. Our findings show that BBR3378 can ameliorate encephalitogenic mechanisms in EAE and antagonize underlying autoimmune mechanisms.
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PMID:A novel aza-anthrapyrazole blocks the progression of experimental autoimmune encephalomyelitis after the priming of autoimmunity. 2196 17