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Progressive multifocal leukoencephalopathy therapy.

David B Clifford1

  • 1Washington University School of Medicine, Box 8111, 660 South Euclid Avenue, Saint Louis, MO, 63110, USA. cliffordd@neuro.wustl.edu.

Journal of Neurovirology
|September 18, 2014
PubMed
Summary
This summary is machine-generated.

Progressive multifocal leukoencephalopathy (PML), a JC virus infection in immune deficiency, now has improved survival. Effective immune reconstitution, not antivirals, is the current practical treatment, balancing JC virus control and preventing immune reconstitution inflammatory syndrome (IRIS).

Keywords:
IRISImmune reconstitution inflammatory syndromeJC virusNatalizumabPMLProgressive multifocal leukoencephalopathy

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Area of Science:

  • Neurovirology
  • Immunology
  • Neurology

Background:

  • Progressive multifocal leukoencephalopathy (PML) is a rare, opportunistic infection caused by the JC virus, typically occurring in individuals with chronic immune deficiency.
  • Therapeutic development for PML has been hindered by disease rarity and patient complexity, with antiviral trials showing limited efficacy.
  • Historically, PML had a poor prognosis, often leading to fatal encephalitis.

Purpose of the Study:

  • To review the current understanding of PML treatment strategies.
  • To highlight the shift in PML prognosis and management approaches.
  • To discuss the role of immune reconstitution versus antiviral therapy in PML.

Main Methods:

  • Review of existing literature on PML.
  • Analysis of clinical trial outcomes for antiviral therapies.
  • Evaluation of immune reconstitution strategies in managing PML.
  • Assessment of the impact of treatments for underlying immune deficiencies (e.g., HIV, natalizumab-associated PML).

Main Results:

  • The prognosis for PML has significantly improved, with a majority of patients now surviving.
  • Effective immune reconstitution strategies, particularly for HIV and natalizumab-induced PML, have driven this improved outlook.
  • Antiviral therapies have not yet demonstrated convincing clinical efficacy in small trials.

Conclusions:

  • Optimal immune reconstitution to control JC virus, while carefully managing immune reconstitution inflammatory syndrome (IRIS), is the most practical current approach to treating PML.
  • While an effective antiviral therapy remains a goal, current management focuses on restoring the patient's immune system.
  • The improved survival rates underscore the importance of addressing the underlying immune deficiency in PML management.