ATP-Binding Cassette Transporters in Inflammatory Brain Disease

A.      Chan; R.      Gold; N.      von Ahsen

Abstract

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.

Keywords: multiple sclerosis, HIV-associated neurocognitive disorders, mitoxantrone, experimental autoimmune encephalomyelitis, cytokines, protease inhibitors, antiretroviral agents, biomarkers, mRNA-expression, drug metabolism