Congratulations to Anton Omelchenko from the Firestein Lab for receiving a fellowship grant of $100,500!
The Graduate Student Fellowship consists of three-year awards of $27,500 per annum with an additional $6,000 for tuition. The aim of this study is to assess the therapeutic efficacy of exosome-based delivery of molecules which inhibit the expression of a gene encoding the sodium-calcium exchanger 1, or NCX1, for the treatment of mild traumatic brain injury. The calcium ion plays an important role in the biological mechanisms, which induce extensive cell damage in the brain after brain trauma. NCX1 is a protein that regulates the amount of calcium present inside of neurons and supporting glial cells. Impaired function of NCX1 contributes significantly to the dysregulation of calcium balance in neurons and glial cells, leading to subsequent cell damage and cell death.
Targeting proteins, such as NCX, in the brain with standard pharmaceutical drugs is difficult due to lack of drug diffusion across the blood brain barrier, a biological system that prevents easy passage of molecules into the brain from the bloodstream. A novel system to introduce therapeutics into the brain is the use of exosomes, nanoscale biological vesicles naturally released by cells for intercellular communication. These vesicles can be harvested from cells, loaded with drugs or other therapeutic molecules, and injected into the bloodstream to deliver the intended therapy to the brain.
For this study, we propose to develop a system using targeted exosomes to deliver a molecular therapy to reduce the amount of NCX protein in neurons in the brain after trauma. Our aim is to test the delivery system in cell culture and mice, and ultimately, assess the therapeutic potential of the system with respect to learning and memory deficits and cell damage in an animal model of mild brain injury. We hope that our proposed work will provide key stepping stones for future therapeutic strategies involving novel delivery of therapeutics for traumatic brain injury.