Secondary progressive multiple sclerosis (MS) is a relentless disease. Over time, patients experience worsening of physical, mental, and mood-related symptoms. There are currently several disease-modifying drugs on the market to help relapsing and remitting MS patients with minor and less severe relapses, but few drugs exist for patients with secondary progressive MS. Yet even as their symptoms progress, the white matter brain lesions found on MRI scans often remain unchanged. However, there is also evidence on the role of inflammation in the gray matter. Suspecting that changes in the brain’s gray matter regions may play a critical role in disease progression, investigators at Brigham and Women’s Hospital conducted an experimental study a few years ago to evaluate differences in microglial cell activity in regions of gray matter of healthy volunteers compared to those with MS. Using a new tracer molecule and PET imaging, the team detected widespread and abnormal activation of microglia in patients with multiple sclerosis and a link to brain atrophy, physical disability and progressive MS.
The study exploited the new radiopharmaceutical [F-18]PBR06, a tracer that targets a specific protein (TSPO) present in activated microglia, the immune cells present in the brain. Many other research projects use carbon C-11, an isotope with a much shorter half-life. However, unlike C-11, the F-18 tracer has a significantly longer half-life and higher clinical potential. For the pilot study, investigators evaluated the results of 12 patients with MS, 7 with relapsing remitting MS and 5 with secondary progressive MS, and compared it to healthy controls using the F-18 tracer. They found more microglial gray matter activation in MS patients than healthy controls, particularly in the hippocampus, parahippocampus, cingulate gyrus and amygdala regions of the brain. These brain regions are known to influence processes such as emotions, memory and cognition, all of which can be affected in MS patients. Structures in the deep gray matter, particularly the thalamus, showed greater activation of microglia in secondary progressive MS, compared to patients with relapsing remitting MS. The thalamus is the station that processes brain functions after processing them.