Circumventing the blood–brain barrier

Abstract

If the brain is the body’s central processing unit, then the blood–brain barrier is its firewall. A specialized network of cells that lines the brain’s vascular system, the blood–brain barrier selectively ushers in nutrients and other essential biomolecules while denying entry to most everything else. But the same system that protects the brain also stymies many therapeutics that could potentially treat disease. Fig. 1. In November 2015, researchers at Sunnybrook Health Sciences Centre in Toronto began a clinical trial to noninvasively breach the blood–brain barrier with focused ultrasound in an attempt to deliver chemotherapy to brain tumors. Image courtesy of Doug Nicholson (Sunnybrook, Toronto). A handful of drugs slip into the brain by passive diffusion—among them, antidepressants and medications for schizophrenia and epilepsy, along with caffeine, alcohol, and nicotine. These molecules are exceedingly small. They also can readily dissolve into the lipid membranes that encase blood–brain barrier cells. But new drug leads of this type are growing more elusive. “Most of the small molecule combinations have been explored,” says biomedical engineer Peter Searson at Johns Hopkins University in Baltimore, MD. Given these challenges, researchers are looking for other ways to slip past the barrier. Brain-penetrating antibodies and viruses could, for example, ferry therapeutic cargo across the border. A few groups are using ultrasound to temporarily open parts of the blood–brain barrier. “Over the last 20 years, blood–brain barrier research went from just a little small cottage industry to people really bringing the newest tools and approaches to bear on problem,” says bioengineer Eric Shusta at the University of Wisconsin–Madison. Finding ways to stealthily shuttle drugs across the blood–brain barrier could have big therapeutic implications. Although attempts to penetrate the barrier have only recently gained steam, the blood–brain barrier concept has been around for more than 100 years. The origins of the idea …