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Natalizumab and PML

2005; Nature Portfolio; Volume: 8; Issue: 10 Linguagem: Inglês

10.1038/nn1005-1275

1546-1726

Richard M. Ransohoff,

Polyomavirus and related diseases

Natalizumab and PMLα4-integrin target, and they prompt the following hypothesis: that natalizumab treatment led to PML by mobilizing infected bone marrow cells, possibly in combination with reduced inflammatory and surveillance trafficking to the CNS.If this hypothesis is correct, agents that do not affect bone marrow will lack this complication, whereas those affecting bone marrow and lymphoid organs (anti-CXCR4, anti-α4 integrin and FTY720, for example) require caution and surveillance.Furthermore, PML may be regarded as an off-target adverse effect, and it remains possible to treat MS patients with agents that address leukocyte trafficking to the CNS.Reduced numbers of cerebrospinal fluid CD4 + T cells could indicate possibly impaired CNS immunosurveillance.This hypothesis needs to be addressed, and many questions, including the prevalence of pathogenic JCV, a possible CNS JCV reservoir, and effects of releasing JCV-infected cells from bone marrow on TCR elements and viral replication, need to be answered.Ultimately, each leukocyte trafficking modulator will have its own liabilities, and we need to avoid being caught 'fighting the last war' against PML as we evaluate other agents.The prize will be to regain momentum in the fight for effective treatment for MS and other inflammatory diseases.