Breaking Into The Brain

The blood-brain barrier protects our neurons from potentially harmful substances circulating in blood, but it also impedes delivery to the brain of many potentially life-saving drugs. Researchers led by Per-Ola Freskgård and Anirvan Ghosh of Hoffmann-La Roche in Basel, Switzerland, report a new tactic for getting drugs to cross this challenging barricade (Neuron 2014, DOI: 10.1016/j.neuron.2013.10.061). They hijacked transport machinery normally used to move essential molecules and nutrients across the blood-brain barrier so that it ferries a potential drug instead. In particular, the team focused on the transferrin receptor, which normally shuttles iron. They attached a potential drug to treat Alzheimer’s disease to an antibody called sFab that binds the transferrin receptor and can be transported across the blood-brain barrier. They showed that the hijacking step enhanced the putative drug’s ability to reach its target behind the barrier by a factor of more than 50. The team argues that their design “could be expanded to other cargos, such as therapeutic growth factors, enzymes, and peptides, and could greatly facilitate the development of a new generation of biotherapeutics for brain disorders.”