The blood-brain barrier is a specialized system of cells that acts as a gatekeeper for the brain. But could it be preventing medication from reaching the areas it's designed to help?

Despite the marvels of modern medicine and an abundance of research advancements, neurological and central nervous system disorders remain some of the most complex medical conditions to treat.

For starters, the causes of conditions like Alzheimer’s and Parkinson’s aren’t entirely known. For other conditions such as epilepsy or multiple sclerosis, there may be an abundance of potential causes, making it difficult to pinpoint any one singular culprit.

Compounding the problem? An unlikely suspect: the brain itself.

The human brain has its own natural defense system – the blood-brain barrier – which at times can actually obstruct the brain from receiving the medications needed to keep neurologic and central nervous system conditions at bay.

The blood-brain barrier is a specialized system of cells that acts as a gatekeeper for the brain, blocking harmful substances from entering and even rejecting harmful substances that break through, all while allowing in necessary nutrients. The barrier is imperative to keeping both the brain and the central nervous system healthy.

But in some cases, the barrier might actually be its own worst enemy.

“The blood-brain barrier causes problems in medication delivery because it treats medications as the enemy, preventing the therapeutic agents from doing the job they’re designed to do,” said Dr. Lester Drewes, professor of biochemistry and molecular biology at the University of Minnesota Medical School’s Duluth campus.

Leaving all the options open

Recently, Drewes and a colleague from the Oregon Health & Science University led an international team of scientists in calling for more research into the drug delivery problem.

According to Drewes, there are a number of approaches currently being studied – some right on the Duluth campus – that could help solve the blood-brain barrier dilemma.

In some areas of the brain, vulnerabilities may offer a way through. Researchers just need to find them, and capitalize on their existence.

Other investigators are studying a “Trojan horse approach” in which therapeutic agents are attached to parts of proteins, such as insulin, that normally cross the barrier. Once inside, they could be engineered to break away and target a disease site.

Researchers also believe that in addition to the blood-brain barrier, additional specialized barriers exist in the brain which function in different ways. Going forward, it will be critical for experts to understand how these barriers act alone and in concert with each other.

“Drug delivery to the brain is extremely complicated,” said Drewes. “Treatment difficulties are only compounded when therapeutic drugs can’t make it beyond the blood-brain barrier. It’ll be critical for researchers across disciplines to work together to find new drug delivery methods and to develop new ways to overcome the barrier.”

Much of this work will likely stem from Drewes’ work at the Duluth campus of the University of Minnesota Medical School.

“The long-term goals of my research are to characterize the process by which nutrients are transported through the cells comprising the blood-brain barrier,” said Drewes. “By understanding these processes, we’ll get key insight into understanding neurological dysfunctions associated with stroke, diabetes and neurodegenerative diseases.”

--- Justin Paquette