The blood-brain barrier acts as a security border for the brain, playing a vital role in protecting the delicate neurons inside. However, its strict admission policy can be a problem when it comes to dispatching drugs to treat brain diseases.
For years, scientists have been trying to find ways to give medical treatments a passport to cross the blood-brain barrier, and a new study outlines one of the most promising approaches yet: a way of controlling the barrier at a molecular level.
A newly developed antibody is able to open the blood-brain barrier for a couple of hours at a time, a window of opportunity for drugs to be delivered. Ultimately, it could make neurological conditions such as Alzheimer’s and multiple sclerosis easier to treat.
“This is the first time we’ve figured out how to control the blood-brain barrier with a molecule,” says physiologist Anne Eichmann from Yale University.
The researchers tapped into what’s known as the Wnt signaling pathway to make this happen. It regulates several important cellular processes, and in this study, the communications network was used to unlock the blood-brain barrier.
Key to the process was the molecule Unc5B, which is involved in regulating exchanges between blood vessels and surrounding tissue. Experiments showed that when this receptor was knocked out in mice, they died as embryos because their vasculature (blood vessel) network failed to develop properly.
What’s more, removing Unc5B also reduced the levels of a protein called Claudin-5, which is vital in building up the junctions of the blood-brain barrier, suggesting that Unc5B could have a role to play in opening up the barrier enough to get drugs through.
Tests on adult mice showed that an absence of Unc5B did indeed leave the blood-brain barrier open. From there, the researchers found their way to the Netrin-1 ligand – a binding substance – that controls how effective Unc5B is. Finally, an antibody was developed to block Netrin-1 and disrupt the Wnt pathway.
“It was quite a fascinating journey, especially the development of our blocking antibodies,” says biologist and the study’s lead author Kevin Boyé, also from Yale. “And seeing that we can open the blood-brain barrier in a very time-sensitive fashion to promote drug delivery.”
Originally discovered in worms, Unc5B hasn’t previously been linked to the function of the Wnt signaling pathway in this way, and it’s an exciting development considering its potential for enabling treatment delivery for all kinds of brain-related conditions.
There’s still work to do though. The effectiveness of the antibody still needs to be tested, and the researchers will also be looking out for any toxicity and side effects that might make it complicated to deliver drugs in this way.
Further down the line, the team hopes that their findings could also be helpful in improving chemotherapy for cancer tumors in the brain. The same antibody might also have potential in terms of being used in other areas of the central nervous system.
“This paves the way to more interesting basic research around how the body builds such a tight barrier to protect its neurons and how it can be manipulated for drug delivery purposes,” says Eichmann.
The research has been published in Nature Communications,