Targeting SPMS: Effect of Teriflunomide Treatment on Microglial Activation in an MS Patient Cohort at Risk of Progression. A [11C]PK11195 Brain PET Study

In Multiple Sclerosis (MS), plaques in the white and grey matter of the brain represent the best known pathological changes of the disease, but a significant inflammation process has also been detected outside these plaques in connection with the disease. This extensive, diffuse inflammatory process correlates with the progression of the disease, measured by EDSS score (Expanded Disability Status Scale status) and reduction in patients' cognitive level. According to neuropathological research, the diffuse inflammatory process outside the plaques is connected with powerful activation of microglia, oxidative stress, and deficiencies in mitochondrial activity. The activation of microglial cells can be measured in vivo in patients using positron-emission tomography (PET) scanning and so-called TSPO radioligands, such as the 11C-PK11195 radioligand. 11C-PK11195 radioligand binds to TSPO molecules, which manifest on the surface of activated, but not un-activated, microglia.

Teriflunomide treatment is expected to slow down the process of increasing microglial activation. TSPO-PET imaging allows in vivo follow-up of the pathogenic process associated with the gradual MS disease evolution, and allows to evaluate whether teriflunomide treatment has an effect on disease progression-related pathology.