Patients With Early Parkinson’s Show Increased Levels of Inflammation Compared to Healthy Controls
Evidence is growing to support the involvement of inflammation in Parkinson’s disease, and researchers are exploring inflammation as a treatment target. Positive results from a Phase 2a trial of carbidopa/levodopa + bezisterim, a compound that targets inflammation, were announced at the Advanced Therapeutics in Movement and Related Disorders Congress® (ATMRD) in June.
Gaps in knowledge about the role of inflammation in Parkinson’s remain. Outstanding questions are whether inflammation causes or is the result of neurodegeneration and its role in predicting cognitive decline. Baseline results from another study were recently published in Movement Disorders in which researchers helped to address these gaps by measuring inflammation and cognition in 58 patients with newly diagnosed and untreated Parkinson’s disease compared to 62 healthy age- and sex-matched controls.
Participants underwent a comprehensive cognitive assessment that included at least two tests in each of the domains of attention, language, memory, executive function, and visuospatial ability. Blood samples were used to assess cytokine and chemokine levels, and participants underwent PET imaging with 18F-DPA-714 to measure central inflammation. A subset of participants (25 with Parkinson’s and 19 controls) consented to the collection of cerebrospinal fluid (CSF) for evaluation of cytokine and chemokine levels.
Patients with Parkinson’s performed significantly worse than controls in measures of visuospatial cognition (P=0.046), visual memory (P=0.054), executive function (P=0.044), and the composite cognitive score (P=0.033).
Blood samples revealed higher levels of the cytokine macrophage inflammatory protein-1β (MIP-1β) in patients compared to controls, and CSF analysis showed higher levels of macrophage inflammatory protein-1α (MIP1α/CCL3) and thymus- and activation-regulated chemokine (TARC/CCL17) in patients vs controls. Patients with Parkinson’s had increased CD4+ T non-regulatory cell percentages, decreased CD4+ T regulatory cell percentages, and higher neutrophil to lymphocyte ratio compared to controls.
Patients with Parkinson’s had higher 18F-DPA-714 binding in six areas of the brain vs healthy controls—the putamen, thalamus, substantia nigra, temporal cortex, parietal cortex, and occipital cortex, indicating increased central inflammation.
“These findings suggest that early, inflammatory changes are associated with neurodegeneration in PD. Longitudinal follow-up of this cohort will be critical to determine the significance of early inflammatory changes and to observe if certain inflammatory changes predict clinical progression,” conclude the study authors.
