Do-Geun Kim, A. Krenz, M. Bynoe
May 1, 2013
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Journal
The Journal of Immunology
Abstract
Multiple sclerosis (MS) is a debilitating neuroinflammatory disease that is characterized by infiltration of inflammatory immune cells into the central nervous system (CNS). Currently, there is no cure for MS and the few available treatments only lessen symptoms in some patients, and can have debilitating side effects. Our lab has pioneered studies demonstrating that blockade of broad spectrum or A2A specific adenosine receptor signaling inhibits lymphocyte infiltration into the CNS and protects mice from a multiple sclerosis animal model called experimental autoimmune encephalomyelitis (EAE). Pegylated adenosine deaminase (PEG-ADA) is an FDA-approved drug used to treat patients with severe combined immune deficiency (SCID) due to a mutation in their adenosine deaminase (ADA) gene which converts adenosine into inosine. In this study, we used PEG-ADA to assess its therapeutic potential to protect progression and alleviate the severity of EAE. We hypothesized that similar to adenosine receptor blockade, depletion of extracellular adenosine by PEG-ADA may lessen the influx of inflammatory immune cells into the brain and protect mice from EAE. Our results showed that indeed mice treated with PEG-ADA developed significantly less severe EAE and had less immune cell infiltration in their brain. Because a common characteristic of MS in general is the invasion of pathogenic immune cells into the CNS, this study has the promising potential to benefit MS patients.