title: Potential risk of progressive multifocal leukoencephalopathy with natalizumab therapy: possible interventions.
abstract: 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.
authors.affiliation: Neurology Section, Medical Service, Veterans Affairs North Texas Health Care System, Dallas, TX, USA. olaf.stuve@utsouthwestern.edu
authors.forename: Olaf
authors.initials: O
authors.lastname: Stüve
authors.forename: Christina M
authors.initials: CM
authors.lastname: Marra
authors.forename: Petra D
authors.initials: PD
authors.lastname: Cravens
authors.forename: Mahendra P
authors.initials: MP
authors.lastname: Singh
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.forename: Amy
authors.initials: A
authors.lastname: Lovett-Racke
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Monson
authors.forename: J Theodore
authors.initials: JT
authors.lastname: Phillips
authors.forename: Jan W Cohen
authors.initials: JW
authors.lastname: Tervaert
authors.forename: Richard A
authors.initials: RA
authors.lastname: Nash
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Bernd C
authors.initials: BC
authors.lastname: Kieseier
authors.forename: Michael M
authors.initials: MM
authors.lastname: Racke
authors.forename: Elliot M
authors.initials: EM
authors.lastname: Frohman
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hemmer
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D006801:Humans; D007275:Injections, Intravenous / Q000379:methods; D016023:Integrins / Q000276:immunology*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000188:drug therapy*; D000069442:Natalizumab; D034741:RNA, Small Interfering / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016023:Integrins; D000069442:Natalizumab; D034741:RNA, Small Interfering