Engineers explore ways to understand, outwit blood-brain barrier

MADISON — With support from the New Frontier Science group of Takeda Pharmaceutical Co., University of Wisconsin–Madison engineers are conducting innovative research that could open new avenues for treating such diseases as Parkinson’s, Alzheimer’s, multiple sclerosis and others.

NFS collaborates with external researchers in an effort to advance innovative technologies and integrate them into future medicines.

“There are tens of millions of people worldwide who suffer from neurological disease, and there aren’t many treatments because of the blood-brain barrier and the obstacle it presents to drug delivery,” says Eric Shusta, a professor of chemical and biological engineering who is one of two UW–Madison co-investigators on the project.

The blood-brain barrier is a unique membrane made up of tightly knit, high-density endothelial cells, which line the inner walls of the capillaries and blood vessels that supply the brain. This barrier can selectively restrict foreign substances — harmful or beneficial — from passing into the brain.

As a result, it’s a major medical hurdle, says Shusta. “If drugs are in the bloodstream, they have a very difficult time accessing the brain because the vasculature is very tight and does not let drug molecules get through,” he says.

Shusta and colleague Sean Palecek, also a UW–Madison professor of chemical and biological engineering, have developed a human pluripotent stem cell-based model that enables them to replicate and study how the blood-brain barrier functions in the body.

Pluripotent stem cells can give rise to virtually any cell type in the body. Through the New Frontier Science collaboration, the researchers are exploring the pathways through which pluripotent stem cells become blood-brain barrier endothelial cells. Not only could they apply that understanding in drug screening tools, they also might use it to develop treatments for diseases, such as stroke, that involve the blood-brain barrier. “If we can understand the molecular mechanisms that allow development of the blood brain barrier, perhaps we can fix those problems as they occur,” says Shusta.