A pilot study published in the Annals of Clinical and Translational Neurology has shown evidence of increasing innate immune burden in patients with progressive multiple sclerosis (MS).
The study revealed higher levels of immune activity in normal-appearing white matter (NAWM) and several gray matter regions in progressive MS patients, compared to healthy controls, on positron emission tomography (PET) imaging.
The immune activity increased over the first 12 months of the study in the areas of the NAWM (P =.01), cortex (P =.04), thalamus (P =.04), and putamen (P =.02) but was not significantly different at 24 months. The authors attributed the lack of significance at the 24-month timepoint to the loss of patients (only 10 of the original 15 completed the study).
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The authors of the study state, “our pilot data suggest that diffuse innate immune activity within the CNS may be increasing over time in patients with progressive multiple sclerosis and could play an active role in the pathogenesis of disease progression. Our data support larger studies dedicated to further explore this pathway and evaluate the association with clinical disability.”
The study imaged levels of the ligand (R)-[N-methyl-11C]PK11195 (PK11195) to estimate immune activity. PK11195 binds to the 18 kDa translocator protein in activated microglia and macrophages. A total of 15 patients with either primary progressive MS (n=6) or secondary progressive MS (n=9) were infused with PK11195 and imaged at several time points throughout the trial. All 15 patients were imaged at baseline and 6 months, while 14 were imaged at 12 months, and only 10 completed the full study duration of 24 months.
A total of 16 age-matched healthy controls were also imaged at baseline for comparison. MRI scans were completed in order to coregister PET scans and expanded disability status scores were also collected to monitor disease progression. No significant changes in EDSS were observed at the 12- (P =.66) or 24-month (P =.86) time points, however, despite the increased immune activity.
Kang Y, Pandya S, Zinger N, Michaelson N, Gauthier SA. Longitudinal change in TSPO PET imaging in progressive multiple sclerosis. Ann Clin Transl Neurol. 2021;(acn3.51431). doi:10.1002/acn3.51431