Objective The societal burden of brain disorders, such as multiple sclerosis (MS), Alzheimer’s and Parkinson’s disease is enormous and is considered one of the world’s most important health challenges. They affect millions of people worldwide and the annual healthcare costs are high and are increasing with the aging population. There is an immediate need to better understand the underlying molecular mechanisms of these disorders. Inflammation is widely recognized to play an important role in many neurological disorders. Next to the response of microglia, the resident immune cells in the central nervous system (CNS), infiltration of monocytes from the blood occurs, but the exact role of monocyte infiltration and the interplay between microglia and monocytes in vivo is still largely unknown. Clinical trials with chemokine receptor type 2 (CCR2) antagonists, aiming to reduce recruitment of monocytes and thereby reducing neuroinflammation, do not show clinical efficacy. Together, this emphasizes the need to unravel the role of infiltrating monocytes in human disease in vivo. Positron emission tomography (PET) is an imaging technique well suited to serve this purpose. I propose to develop new PET tracers targeting CCR2 as a tool to visualize infiltration of monocytes in the CNS in vivo to help elucidate their role in disease. Newly developed tracers will be evaluated in vitro, ex vivo and in vivo in an animal model of MS. A successful PET tracer will contribute to a better understanding of monocyte infiltration in disease in vivo and could ultimately serve as an important tool to guide drug development and evaluate novel disease-modifying therapies and therapies inhibiting monocyte infiltration. On a personal level, the proposed project will have a significant impact on my career, as new skills in neuroimaging, computer-aided drug design and in vitro target validation techniques will complement my previous expertise in organic chemistry, radiochemistry and PET tracer development. Fields of science medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverymedical and health sciencesbasic medicineneurologydementiaalzheimermedical and health sciencesbasic medicinemedicinal chemistrymedical and health sciencesbasic medicineneurologymultiple sclerosismedical and health sciencesbasic medicineimmunology Programme(s) HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme Topic(s) HORIZON-MSCA-2021-PF-01-01 - MSCA Postdoctoral Fellowships 2021 Call for proposal HORIZON-MSCA-2021-PF-01 See other projects for this call Funding Scheme HORIZON-AG-UN - HORIZON Unit Grant Coordinator STICHTING VUMC Net EU contribution € 203 464,32 Address De boelelaan 1117 1081 HV Amsterdam Netherlands See on map Region West-Nederland Noord-Holland Groot-Amsterdam Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window EU contribution No data
