Role of Microglia in the Pathogenesis of Progressive Multiple Sclerosis

Protocol title: Role of microglia in the pathogenesis of progressive multiple sclerosis

Rationale of the study: The investigators have demonstrated earlier a statistically significant correlation between TSPO-binding and EDSS in a heterogeneous MS-population comprising both early RRMS and late secondary progressive multiple sclerosis (SPMS) patients. Now the investigators aim to evaluate whether TSPO-imaging correlates to EDSS and other disease progression-related clinical and paraclinical parameters in a homogenous cohort of 40-50-year old MS-patients, who are at risk of progression. The A2A-AR expression in this cohort will also be studied using the A2A-AR-binding radioligand 11C-TMSX. The study cohort will also form the basis for a later follow-up study, which will be performed to evaluate the prognostic value of baseline TSPO-imaging in terms of disease progression. TSPO-imaging could thus be used as an imaging biomarker to help identifying patients to therapeutically prevent progression of MS. At the 5 year time point synaptic density will be evaluated using 11C-UCB-J radioligand and PET imaging.

Study population: The study population will consist of a clinically homogenous group of 25 relapsing remitting multiple sclerosis (RRMS) patients with MS-diagnosis for at least 5 years, age 40-50 years, who may be using any first-line MS therapy. The patients will be recruited from the outpatient clinic of the Division of Clinical Neurosciences of the University Hospital of Turku, Finland. In addition the investigators will image a group of 10 age- and sex-matched healthy control subjects for comparison.

Study Objectives Primary: To evaluate how TSPO-ligand binding in the normal appearing white matter (NAWM) correlates to EDSS.

Secondary: 1) To evaluate how TSPO-ligand binding in the NAWM at baseline correlates to other standard clinical and paraclinical parameters typically associated with disease progression 2) To evaluate how 11C-TMSX-binding (to A2A-AR) correlates to the clinical and paraclinical parameters, and to TSPO-binding. 3) To evaluate how synaptic density evaluated using 11C-UCB-J binding correlates to patients cognitive functions.