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Review
. 2024 May;23(5):534-544.
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

Irene Cortese  1 , Gina Norato  2 , Patrick R Harrington  3 , Therri Usher  4 , Ilaria Mainardi  5 , Guillaume Martin-Blondel  6 , Paola Cinque  5 , Eugene O Major  7 , Virginia Sheikh  3
Affiliations
Review

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

Irene Cortese et al. Lancet Neurol. 2024 May.

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.

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Conflict of interest statement

Declaration of interests IC reports providing free consultative advice to Cellevolve and is a shareholder in Nouscom and Keires, outside the submitted work. All other authors declare no competing interests.

Figures

Figure 1:
Figure 1:. Framework for use of Biomarkers of PML in Clinical Trials
Virological burden, tissue destruction and immune reconstitution reflect key pathophysiological features of PML. Quantitative measures of these features could serve as biomarkers in clinical trials—eg, for diagnosis, as trial entry criteria, for prognosis, and to predict response to treatment. To support the use of any candidate biomarker, robust evidence needed to demonstrate clinical relevance, reliability across PML subpopulations, and assay standardization with definition of performance metrics.
See this image and copyright information in PMC

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