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Ther Adv Neurol Disord. 2015 Nov;8(6):255-73. doi: 10.1177/1756285615602832.

Progressive multifocal leukoencephalopathy: current treatment options and future perspectives.

Author information

1
MedImmune, Gaithersburg MD, USA.
2
AstraZeneca, Mölndal, Sweden.
3
F. Hoffmann-La Roche, Basel, Switzerland.
4
The Progressive Multifocal Leukeoncephalopathy Consortium Secretariat, Drinker Biddle & Reath LLP, 1500 K Street NW, Washington, DC, USA.

Abstract

Progressive multifocal leukoencephalopathy (PML) is a rare but debilitating and frequently fatal viral disease of the central nervous system, primarily affecting individuals with chronically and severely suppressed immune systems. The disease was relatively obscure until the outbreak of HIV/AIDS, when it presented as one of the more frequent opportunistic infections in this immune deficiency syndrome. It attracted additional attention from the medical and scientific community following the discovery of significant PML risk associated with natalizumab, a monoclonal antibody used for treatment of relapsing-remitting multiple sclerosis. This was followed by association of PML with other immunosuppressive or immunomodulating drugs. PML is currently untreatable disease with poor outcomes, so it is a significant concern when developing new immunotherapies. Current prophylaxis and treatment of PML are focused on immune reconstitution, restoration of immune responses to JC virus infection, and eventual suppression of immune reconstitution inflammatory syndrome. This approach was successful in reducing the incidence of PML and improved survival of PML patients with HIV infection. However, the outcome for the majority of PML patients, regardless of their medical history, is still relatively poor. There is a high unmet need for both prophylaxis and treatment of PML. The aim of this review is to discuss potential drug candidates for prophylaxis and treatment of PML with a critical review of previously conducted and completed PML treatment studies as well as to provide perspectives for future therapies.

KEYWORDS:

HIV; IL-7; IRIS; JCV; PML; PML-IRIS; anti-viral; immunosuppression; interferon; natalizumab; prophylaxis; treatment; vaccine

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