$125,000 awarded to Dr. Derrick Gibbings, University of Ottawa, with co-investigators Dr. Baptiste Lacoste and Dr. Maxim Berezovski, University of Ottawa.
Gene mutations leading to disease often produce toxic proteins that, in the case of the inherited form of ALS, cause motor neurons to die. One of the most significant advancements in therapy over the past several years is the ability to use technology to target genetic diseases. Scientists have developed many treatments that can reduce the amount of these toxic proteins, but one of the major challenges has been delivering treatments to central nervous system. Our bodies have a specialized barrier called the blood-brain barrier that makes it very difficult to introduce drugs into the brain or nervous system.
Exosomes are microscopic bubbles that our body uses to transport substances from cell to cell. For years, researchers have tried to use exosomes in lab experiments to deliver therapies through the bloodstream, but the amount of treatment that can fit into each exosome has been a major limitation. Dr. Gibbings and colleagues have recently discovered a system to squeeze 1,000 times more treatment into each exosome. In this study, they will first test the ability of their system to deliver treatment to the brain after injection into the bloodstream, measure how many exosomes reach the destination and determine the cellular processes that allow the therapies to cross the blood-brain barrier. Second, they will use a well-studied ALS mouse model with mutations in a gene called SOD1 to see if exosomes loaded with a SOD1-targeted treatment can effectively reduce the levels of toxic, mutant SOD1 proteins. Throughout the project, they will continue working on modifying the exosomes to further enhance their ability to move treatments across the blood-brain barrier. If successful, this initial set of tests may provide the evidence needed to advance to testing exosome-delivered treatments in human clinical trials in the future.