Journal
CURRENT PHARMACEUTICAL DESIGN
Volume 17, Issue 26, Pages 2803-2807Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/138161211797440131
Keywords
multiple sclerosis; HIV-associated neurocognitive disorders; mitoxantrone; experimental autoimmune encephalomyelitis
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Funding
- German Ministry for Education and Research (BMBF, German Competence Network Multiple Sclerosis (KKNMS, CONTROL MS) [01GI0914]
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Owing to therapeutic progress, the role of ABC-transporters in infectious and autoimmune inflammatory CNS-diseases has recently gained considerable attention. In HIV-encephalitis and HIV-associated neurocognitive disorders, ABC-transporters are discussed to contribute to limited CNS-penetration and -retention of antiviral agents. In multiple sclerosis and its animal model experimental autoimmune encephalomyelitis, ABC-transporters may be involved in pathogenesis and treatment response alike. A prospective pharmacogenetic study is currently underway to examine the predictive role of genetic variations in ABC-transporters for treatment response and adverse events to mitoxantrone, a therapeutic agent used in aggressive MS. These approaches may aid in individualized treatment with this cytostatic anthracenedione, addressing its narrow therapeutic index with potentially fatal side effects. Finally, understanding regulation and function of ABC-transporters under inflammatory conditions may also optimize ABC-transporter-related treatment strategies in other neurological diseases (e. g. neurodegenerative, and neurovascular) where neuroinflammatory mechanisms have gained considerable attention as important contributors to pathogenesis.
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