The objective of this study is to examine the risk factors and natural course of JCV
infection and progressive multifocal leukoencephalopathy (PML). PML is a devastating,
demyelinating neurological disease affecting the brain of patients with a compromised
immune system. It is caused by reactivation of JC virus (JCV), a small DNA virus that
infects the majority of the population without clinical significance. There are currently
no treatments available for PML.
We plan to study patients with suspected or confirmed PML with different underlying
conditions including patients on immune-modulatory therapies for multiple sclerosis (MS),
rheumatologic diseases or other autoimmune diseases, as well as patients with HIV
infection or other conditions leading to a compromised immune system. Patients will be
seen at defined time points during their disease course and detailed assessments will be
performed to collect clinical and imaging data. Blood, cerebrospinal fluid (CSF) and
urine will also be collected at these time points to evaluate the behavior and biology of
the JCV and the patients immune responses to the infection. These tests will lead to a
better understanding of the pathophysiology of PML and the course of this disease in
different patient groups. Additionally, we will recruit a patient control cohort
represented by patients with impaired immune function for any cause and considered at
risk for development of PML, and a healthy volunteer cohort. The purpose of these
additional cohorts is to explore and validate biomarkers for risk of development of PML
and early diagnosis. Additionally, the healthy volunteer cohort may be screened and
evaluated as possible donors of peripheral blood mononuclear cells (PBMC) for manufacture
of virus-specific T cells.
The detailed characterization described above will be used to help identify:
Clinical, imaging, and/or laboratory features pathognomonic of JCV infection and
disease course that may aid in earlier diagnosis and appropriate intervention
Clinical, imaging, and/or laboratory features of JCV infection and disease course
that are predictive of clinical outcomes
This information will be integrated to develop a clinically relevant, disease-specific
assessment scale of PML, which is currently not available. Such a scale would be a useful
tool for the clinical management of patients (i.e., for development of standards of
care), as well as for clinical trial design and interpretation.
The long-term objectives of this study are to improve the understanding of the disease
course and underlying pathophysiology, to identify subgroups with different prognosis
and/or susceptibility to interventions, and to help identify therapeutic targets and/or
intervention strategies. Equally important, these efforts will allow development of a
repository of cryopreserved biological samples that will be used for validation of
candidate biomarkers in future studies.