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Potential Risk of Progressive Multifocal Leukoencephalopathy With Natalizumab Therapy

Possible Interventions

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

Arch Neurol. 2007;64:169-176.

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.


Author Affiliations: Neurology Section, Medical Service, Veterans Affairs North Texas Health Care System, Dallas (Dr Stüve); Departments of Neurology (Drs Stüve, Cravens, Singh, Hu, Monson, and Frohman) and Ophthalmology (Dr Frohman) and Center for Immunology (Drs Stüve and Monson), The University of Texas Southwestern Medical Center at Dallas; Department of Neurology, Heinrich Heine University, Düsseldorf, Germany (Drs Stüve, Hartung, Kieseier, and Hemmer); Department of Neurology, University of Washington, Seattle (Dr Marra); Multiple Sclerosis Center at Texas Neurology, Dallas (Dr Phillips); Department of Clinical and Experimental Immunology, University Hospital Maastricht, Maastricht, the Netherlands (Dr Cohen Tervaert); Fred Hutchinson Cancer Research Center, Seattle (Dr Nash); and Department of Neurology, The Ohio State University Medical Center, Columbus (Drs Lovett-Racke and Racke).