Project description
Paving the way for drug development and treatment of brain diseases
Microglia are brain-specific immune cells that play an important role in several brain diseases involving neuroinflammation, such as multiple sclerosis, Alzheimer’s and Parkinson’s disease. During an inflammation in the brain, microglia become activated. This is a dynamic process in which microglia can either stimulate (pro-inflammatory) or reduce (anti-inflammatory) the inflammation. In the EU-funded MIM project, scientists will develop a positron emission tomography (PET) tracer for selective imaging of anti-inflammatory microglia. In combination with a previously developed PET tracer for pro-inflammatory microglia, the dynamical changes in microglia activation can be monitored and measured in the onset and progression of disease. This essential insight can pave the way for drug development and treatment opportunities of brain diseases and thereby be an important milestone in the work towards addressing one of the fastest growing health concerns in today’s society.
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. Particularly, the important role of the brain-specific immune cells called microglia needs to be unravelled. Microglia become activated upon inflammation in the brain and its activation covers a wide spectrum of activation states, ranging from stimulating the inflammation (pro-inflammatory status) to reducing the inflammation (anti-inflammatory status). To fill the current knowledge gaps regarding the role and regulation of the different activation states of microglia, I will use positron emission tomography (PET) imaging. My host institution has recently succeeded in developing a PET tracer for imaging pro-inflammatory microglia. However, there is no complementary tracer existing for selective imaging of the anti-inflammatory status. In the proposed project, I will develop a PET tracer targeting the P2Y12 receptor, a receptor over-expressed on anti-inflammatory microglia. To achieve this, I will use an interdisciplinary approach spanning from computational medicinal chemistry through synthetic organic chemistry and radiochemistry to in vitro and eventually in vivo evaluation studies in an animal model for MS. A successful PET tracer will find widespread application in the research regarding brain disorders and ultimately guide drug development and treatment opportunities. On a personal level, the proposed project will have a substantial impact on my career, as new skills in neuroimaging, computer-aided drug design and in vitro evaluation techniques will complement my previous expertise in organic chemistry, radiochemistry and PET tracer development.
Fields of science
- medical and health sciencesbasic medicinepharmacology and pharmacydrug discovery
- natural scienceschemical sciencesorganic chemistry
- medical and health sciencesbasic medicinemedicinal chemistry
- natural scienceschemical sciencesnuclear chemistryradiochemistry
- medical and health sciencesbasic medicineneurologymultiple sclerosis
Programme(s)
Funding Scheme
MSCA-IF-EF-ST - Standard EFCoordinator
1081 HV Amsterdam
Netherlands