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Natalizumab-treated patients at high risk for PML persistently excrete JC polyomavirus

Milton H Werner1, DeRen Huang2

  • 1Inhibikase Therapeutics, Inc., 3350 Riverwood Pkwy SE, Ste 1900, Atlanta, GA, 30339, USA. mhwerner@inhibikase.com.

Journal of Neurovirology
|May 21, 2016
PubMed

Insights

Natalizumab treatment for multiple sclerosis can be linked to JC polyomavirus (JCV) shedding, particularly in patients with a high JCV antibody index. This finding connects JCV infection to progressive multifocal leukoencephalopathy (PML) risk factors.

Area of Science:

  • Neuroimmunology
  • Virology
  • Infectious Diseases

Background:

  • Natalizumab is an effective treatment for relapsing multiple sclerosis (MS).
  • JC polyomavirus (JCV) infection is a known risk factor for natalizumab-associated progressive multifocal leukoencephalopathy (PML).
  • Monitoring JCV in patients treated with natalizumab is crucial for risk stratification.

Purpose of the Study:

  • To investigate the prevalence and characteristics of JC polyomavirus (JCV) viruria in natalizumab-treated multiple sclerosis (MS) patients.
  • To determine the relationship between JCV urinary excretion and the JCV antibody index.
  • To assess the implications of JCV shedding for PML risk in MS patients.

Main Methods:

  • Screening of 63 natalizumab-treated MS patients for JCV viruria.
  • Longitudinal sampling of urinary-positive patients for up to 24 weeks.
  • Utilizing methods to differentiate between encapsidated JCV and naked viral DNA.

Main Results:

  • 17.5% of natalizumab-treated MS patients were found to excrete JCV in urine.
  • Urinary JCV excretion was predominantly observed in patients with a high JCV antibody index (≥2.0), exceeding 73% in this subgroup.
  • The prevalence of urinary excretion aligns with general population levels.

Conclusions:

  • Active JCV infection is more common in natalizumab-treated MS patients with a high JCV antibody index.
  • This suggests a direct link between JCV infection, high antibody levels, and increased risk of developing PML.
  • Findings highlight the importance of monitoring JCV status in natalizumab-treated MS patients.
Keywords:
JCVNatalizumabProgressive Multifocal Leukoencephalopathy (PML)Risk factorsTysabri

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