Grant: Collaborative Health Research Projects (NSERC partnered)

One third of Canadians of all ages will be affected by a brain disease during his or her lifetime. While the population is getting older, the risk of suffering from Alzheimer, stroke, Parkinson, etc. increases exponentially after age 65. Most people do not realize that the socioeconomic burden of brain diseases dwarf those of cancer and cardiovascular disease combined. Unfortunately, the research and development of new drugs for brain diseases lags behind. The main problem resides in the fact that the blood-brain barrier (BBB) severely restricts the passage of drugs from the blood to the brain. The vast majority of advanced drugs are too large to pass through the BBB and virtually all strategies developed so far to cross the BBB without damaging it have failed in humans. Indeed, the brain is like a walled city, in which the BBB represents the wall surrounding the city. The total length of the BBB of a normal human brain spans approximately 600 km. Here, we are proposing to generate new vectors and determine which one is the best to target the natural transport systems located in the BBB. These transport systems are the equivalent of the guarded gates in the walled city analogy, as they allow the entry of their friends. Then, these vectors will be conjugated to nanoparticles to ferry drugs inside cells of the BBB. We will then verify with advances techniques whether our vectorized nanoparticles stay in the BBB or penetrate deeper in the brain. Such a tactic is reminiscent of the Trojan horse strategy because the nanoparticles are built to trick the brain's screening system (or city guards). Therefore, the present study could lead to the development of new brain drug delivery systems for clinical applications in Alzheimer's disease and many other brain disorders.