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Editorial |

The Road Not Taken Antigen-Specific Therapy and Neuroinflammatory Disease

Lawrence Steinman, MD1
[+] Author Affiliations
1Department of Neurology, Stanford University Medical Center, Stanford, California
JAMA Neurol. 2013;70(9):1100-1101. doi:10.1001/jamaneurol.2013.3553.
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Ninety-seven years ago, Robert Frost wrote The Road Not Taken, beginning famously, “Two roads diverged in a yellow wood, And sorry I could not travel both.”1 In 2013, the pharmaceutical industry has largely chosen 1 road for therapy of neuroinflammatory disorders including multiple sclerosis (MS), neuromyelitis optica (NMO), and myasthenia gravis (MG). The pharmaceutical path repurposes monoclonal antibodies originally approved for treatment of myeloid malignancies or redirects small-molecule drugs that first were tried for suppression of immunological rejection of transplanted organs. Some of the leading candidates for therapy of MS, NMO, and MG include anti-CD20, an approach pioneered for treatment of B-cell lymphoma2,3; anti-CD52, an approach first approved for chronic lymphocytic leukemia4; and sphingosine phosphate modulation, an approach first tried for transplant rejection.5 On the “other road,” “the one less traveled by,”1 only a few medical scientists are attempting to tolerize the immune system to those autoantigens that provoked the neuroinflammatory condition. In this issue of JAMA Neurology, Walczak and colleagues6 describe promising results with delivery of 3 myelin peptides, myelin basic protein peptide 85-99, proteolipid protein peptide 139-151, and myelin oligodendroglial glycoprotein 35-55, through the skin, building on earlier work. Their results indicate that they are obtaining some of the sought-after effects of immunological tolerance in relapsing-remitting MS (RRMS).

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