期刊
NATURE REVIEWS DRUG DISCOVERY
卷 4, 期 6, 页码 510-U3出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nrd1752
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Immunologists have long hypothesized that particular 'molecular addresses' govern lymphocyte entry to a given organ. In 1992, α 4β 1 integrin was identified as the key molecule involved in homing to inflamed regions of the brain. An antibody to α 4β 1integrin blocked paralysis in an animal model of multiple sclerosis, and the humanized monoclonal antibody natalizumab, which binds α 4β 1 integrin, reduced relapses 66% in clinical trials in multiple sclerosis. Three months after its expedited approval by the FDA, natalizumab was removed from the market after two cases of deadly progressive multifocal leukoencephalopathy were reported among the few thousand patients who had taken this drug in those clinical trials.
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