Berg Brain Entry and Exit Consortium: Assessment of Antibody-Based Drug Trafficking Across the Blood-Brain Barrier Via Skull-Meninges Connections

The central nervous system is separated from the rest of the body by various barriers, including the blood-brain barrier, which maintains the highly controlled environment needed for proper CNS function. The BBB can be impaired in Alzheimer’s disease. It is a challenge to deliver medical compounds across the blood-brain barrier. Therapies relying on antibody engagement with a target of interest are a novel class of drugs that is promising. These antibodies belong to the adaptive immune system and can be tailored to act on proteins involved in the progression of Alzheimer’s disease. Large molecules, like antibodies, largely are excluded from entering the brain under normal conditions. This research team specializes in tissue-clearing methods that render the entire body of a mouse transparent. This system allows visualization of the brain inside the intact skull without disrupting the fine structures that surround and separate the brain from the rest of the body. This project will investigate the distribution of antibodies in a mouse model of AD to find improved ways to deliver these promising new drugs across the blood-brain barrier to the brain.