Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Nov;8(6):255-73.
doi: 10.1177/1756285615602832.

Progressive multifocal leukoencephalopathy: current treatment options and future perspectives

Dejan Pavlovic  1 , Andriani C Patera  1 , Fredrik Nyberg  2 , Marianne Gerber  3 , Maggie Liu  4 ; Progressive Multifocal Leukeoncephalopathy Consortium
Affiliations
Review

Progressive multifocal leukoencephalopathy: current treatment options and future perspectives

Dejan Pavlovic et al. Ther Adv Neurol Disord. 2015 Nov.

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.

PubMed Disclaimer

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dejan Pavlovic and Andriani Patera are employees of MedImmune, the global biologics research and development arm of AstraZeneca, and own stock in AstraZeneca. Fredrik Nyberg is an employee of and owns stock in AstraZeneca, he is also an employee of University of Gothenburg (Gothenburg, Sweden). Marianne Gerber is employee of and owns stock in F. Hoffmann-La Roche Ltd. AstraZeneca/MedImmune and Roche are PML Consortium member companies. D. Pavlovic, F. Nyberg, and M. Gerber are members of the PMLC Clinical Working Group. A. Patera is a member of the PMLC Preclinical Working Group. Maggie Liu is an employee of Drinker Biddle & Reath, LLP, which serves as the PML Consortium Secretariat, and has no conflict of interest to report.

References

    1. Alstadhaug K., Croughs T., Henriksen S., Leboeuf C., Sereti I., Hirsch H., et al. (2014) Treatment of progressive multifocal leukoencephalopathy with interleukin 7. JAMA Neurol 71: 1030–1035. - PubMed
    1. Antoniol C., Jilek S., Schluep M., Mercier N., Canales M., Le Goff G., et al. (2012) Impairment of JCV-specific T-cell response by corticotherapy: effect on PML-IRIS management? Neurology 79(23): 2258–2264. - PubMed
    1. Astrom K., Mancall E., Richardson E., Jr (1958) Progressive multifocal leuko-encephalopathy; a hitherto unrecognized complication of chronic lymphatic leukaemia and Hodgkin’s disease. Brain 81(1): 93–111. - PubMed
    1. Atwood W. (2001) A combination of low-dose chlorpromazine and neutralizing antibodies inhibits the spread of JC virus (JCV) in a tissue culture model: implications for prophylactic and therapeutic treatment of progressive multifocal leukencephalopathy. J Neurovirol 7: 307–310. - PubMed
    1. Agostini H., Ryschkewitsch C., Singer E., Stoner G. (1997) JC virus regulatory region rearrangements and genotypes in progressive multifocal leukoencephalopathy: two independent aspects of virus variation. J Gen Virol 78: 659–664. - PubMed