Thinking without thinking about natalizumab and PML

The novel multiple sclerosis (MS) therapeutic natalizumab has taken neurologists and their MS patients on a roller-coaster ride: initial encouraging efficacy data led to expedited release in the United States, followed by suspension of dosing with the unexpected occurrence of progressive multifocal leukoencephalopathy (PML) in three clinical trial participants. The drug was re-released in 2006, in a restricted distribution format. Aside from PML, natalizurnab treatment was not associated with opportunistic infections, suggesting the possibility that PML in these individuals was mechanism-based, and was not a consequence of generalized immuno suppression. This commentary proposes a hypothesis to account for PML in natalizurnab-treated patients. (C) 2007 Elsevier B.V All rights reserved.