Biomarkers for progressive multifocal leukoencephalopathy: emerging data for use of JC virus DNA copy number in clinical trials

Irene Cortese; Gina Norato; Patrick R Harrington; Therri Usher; Ilaria Mainardi; Guillaume Martin-Blondel; Paola Cinque; Eugene O Major; Virginia Sheikh

doi:10.1016/S1474-4422(24)00099-1

Biomarkers for progressive multifocal leukoencephalopathy: emerging data for use of JC virus DNA copy number in clinical trials

Lancet Neurol. 2024 May;23(5):534-544. doi: 10.1016/S1474-4422(24)00099-1.

Authors

Irene Cortese¹, Gina Norato², Patrick R Harrington³, Therri Usher⁴, Ilaria Mainardi⁵, Guillaume Martin-Blondel⁶, Paola Cinque⁵, Eugene O Major⁷, Virginia Sheikh³

Affiliations

¹ Experimental Immunotherapeutics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. Electronic address: corteseir@ninds.nih.gov.
² Clinical Trials Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
³ Division of Antivirals, Office of Infectious Diseases, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
⁴ Division of Biometrics IV, Office of Biostatistics, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
⁵ Unit of Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
⁶ Service des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire de Toulouse, Toulouse, France; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), INSERM UMR1291-CNRS UMR5051, Université Toulouse III, Toulouse, France.
⁷ Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.

PMID: 38631769
DOI: 10.1016/S1474-4422(24)00099-1

Abstract

Progressive multifocal leukoencephalopathy is a rare but devastating demyelinating disease caused by the JC virus (JCV), for which no therapeutics are approved. To make progress towards addressing this unmet medical need, innovations in clinical trial design are needed. Quantitative JCV DNA in CSF has the potential to serve as a valuable biomarker of progressive multifocal leukoencephalopathy disease and treatment response in clinical trials to expedite therapeutic development, as do neuroimaging and other fluid biomarkers such as neurofilament light chain. Specifically, JCV DNA in CSF could be used in clinical trials as an entry criterion, stratification factor, or predictor of clinical outcomes. Insights from the investigation of candidate biomarkers for progressive multifocal leukoencephalopathy might inform approaches to biomarker development for other rare diseases.

Publication types

Review

MeSH terms

Biomarkers
Clinical Trials as Topic
DNA Copy Number Variations
DNA, Viral / genetics
Humans
JC Virus*
Leukoencephalopathy, Progressive Multifocal*

Substances

Biomarkers
DNA, Viral