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Til bevillingsoversigt

Harnessing the beneficial potential of neuroinflammation

Carlsbergfondets internationaliseringsstipendier

What

Multiple sclerosis is a disabling disease where brain and spinal cord are attacked by the immune system leading to destruction of the axons and myelin sheaths. This damage is insufficiently repaired by the body due to ongoing inflammation. The immune cells of the brain and spinal cord (microglia) play a major part in this inflammation. Recently, activated microglia were linked to repair and protection. This project aims to explore the reparative potential of activated microglia. I will first examine the mechanism behind the repair and protection offered by these cells. I will then identify drugs that will promote this activation in patients.

Why

Recently, microglia have attracted much attention within the scientific community for their great potential for protection and repair. Dr. Yong's research group has recently identified an experimental way to activate microglia. These microglia showed increased reparative functions compared to conventionally activated microglia. To identify drugs that will induce this strongly reparative microglia subset in patients, we need to increase our knowledge of the mechanism behind the beneficial functions. Identification of drugs that generates the reparative microglia subset is a step forward in the fight against multiple sclerosis. Furthermore, the drug will have potential benefits for all patients with brain or spinal cord damage such as stroke or spinal cord injury.

How

I will use a combination of cell culture experiments and different animal models for multiple sclerosis. These methods will help me to characterize the strongly beneficial microglia and elucidate the mechanism behind the reparative function. I will then test a library of pre-approved therapies in human cell culture experiments to identify candidates that could induce these reparative microglia in patients. These candidates will then be tested using the animal models mentioned above to confirm their beneficial effect in a living organism.

SSR

Denmark and Canada are among the countries with the highest prevalence of multiple sclerosis. Right now, the approved therapies for multiple sclerosis do not prevent accumulation of damage, it is therefore of utmost importance to identify therapies that can help prevent this. Identifying ways to harness the process of self-repair in the brain and spinal cord will ultimately help many patients with brain or spinal cord damage and not just multiple sclerosis patients. This project will help lift the socioeconomic burden associated with disability. Using a pre-approved therapy will strongly reduce the time it normally takes from identification of a potential drug candidate to use in the clinic. Therefore, it will reduce the time before this project will be beneficial for patients.