Potential risk of progressive multifocal leukoencephalopathy with natalizumab therapy: Possible interventions

Olaf Stuve, Christina M. Marra, Petra D. Cravens, Mahendra P. Singh, Wei Hu, Amy Lovett-Racke, Nancy L Monson, J. Theodore Phillips, Jan W. Cohen Tervaert, Richard A. Nash, Hans Peter Hartung, Bernd C. Kieseier, Michael M. Racke, Elliot Frohman, Bernhard Hemmer

Research output: Contribution to journalReview article

60 Scopus citations


Natalizumab (Tysabri) is an effective therapy for multiple sclerosis. Recently, 3 patients who were treated with natalizumab developed progressive multifocal leukoencephalopathy (PML), an opportunistic infection of the brain with the polyomavirus JC. The pathogenesis of natalizumab-associated PML may be different from that of PML not associated with the drug. We reviewed biologically feasible interventions for patients diagnosed as having PML or other infections while receiving natalizumab therapy. Existing interventions include antiviral treatment, immunomodulatory therapies, hematopoietic growth factors, plasma exchange, intravenous immunoglobulins, and leukapheresis and autotransfusion of leukocytes. In addition, we examined the feasibility of experimental therapies, including small interfering RNA, the in vivo use of antiserum, and recombinant natalizumab-blocking molecules. There is only circumstantial evidence that any of the proposed treatments will benefit patients with multiple sclerosis treated with natalizumab who may develop PML. In addition, the expected incidence of PML in this patient population will likely be too low to test any of the proposed interventions in a controlled manner. Because it is currently impossible to identify patients at risk, and thus to prevent PML as a consequence of natalizumab therapy, it is important that neurologists be aware of possible therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)169-176
Number of pages8
JournalArchives of neurology
Issue number2
StatePublished - Feb 2007

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology

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    Stuve, O., Marra, C. M., Cravens, P. D., Singh, M. P., Hu, W., Lovett-Racke, A., Monson, N. L., Phillips, J. T., Cohen Tervaert, J. W., Nash, R. A., Hartung, H. P., Kieseier, B. C., Racke, M. M., Frohman, E., & Hemmer, B. (2007). Potential risk of progressive multifocal leukoencephalopathy with natalizumab therapy: Possible interventions. Archives of neurology, 64(2), 169-176. https://doi.org/10.1001/archneur.64.2.169