In this issue of the Journal, there are reports describing in detail three patients in whom progressive multifocal leukoencephalopathy (PML) developed during treatment with natalizumab, a humanized monoclonal antibody against α₄ integrins.¹–³ These patients were among 3000 who had participated in clinical trials of natalizumab for the treatment of multiple sclerosis or Crohn's disease. PML is a deadly opportunistic infection of the central nervous system (CNS) for which there is no specific treatment. It is caused by reactivation of a clinically latent JC polyomavirus infection. This virus infects and destroys oligodendrocytes, leading to multifocal areas of demyelination and . . .