Mouse study reveals new method to unlock the blood-brain barrier

The blood-brain barrier acts as a safety boundary for the brain, playing a vital role in protecting the delicate neurons within. However, its strict admissions policy can be a problem when it comes to sending drugs to treat brain diseases.

For years, scientists have been trying to find ways to give medical treatments a passport to crossing the blood-brain barrier, and a new study describes one of the most promising approaches to date: a way to control the barrier. at the molecular level.

A newly developed antibody is able to open the blood-brain barrier for a few hours at a time, a window of opportunity for drug delivery. Ultimately, it could aid in the treatment of neurological diseases such as Alzheimer’s disease and multiple sclerosis.

“This is the first time that we have discovered how to control the blood-brain barrier with a molecule,” explains physiologist Anne Eichmann from Yale University.

The researchers tapped into something called the Wnt signaling pathway to do this. It regulates several important cellular processes, and in this study the communication network was used to unlock the blood-brain barrier.

Key to the process was the Unc5B molecule, involved in regulating exchanges between blood vessels and surrounding tissues. Experiments have shown that when this receptor was knocked out in mice, they died as embryos because their vasculature (blood vessels) did not develop properly.

Additionally, deletion of Unc5B also reduced levels of a protein called Claudin-5, which is essential for building blood-brain barrier junctions, suggesting that Unc5B may play a role in the opening of the barrier sufficient to obtain drugs. by.

Tests on adult mice showed that an absence of Unc5B actually left the blood-brain barrier open. From there, the researchers found their way to the ligand Netrin-1 – a binding substance – which controls the effectiveness of Unc5B. Finally, an antibody was developed to block netrin-1 and disrupt the Wnt pathway.

“It’s been a pretty fascinating journey, especially the development of our blocking antibodies,” says biologist and lead study author Kevin Boyé, also from Yale. “And to see that we can open the blood-brain barrier in a very time-sensitive way to promote drug delivery.”

Originally discovered in worms, Unc5B has never been linked to the function of the Wnt signaling pathway in this way, and this is an exciting development given its potential to enable delivery of treatments for all kinds of brain-related conditions.

There is still work to be done however. The antibody’s effectiveness has yet to be tested, and researchers will also look for any toxicity and side effects that might complicate administering drugs in this way.

Later, the team hopes their findings could also be useful in improving chemotherapy for cancerous tumors in the brain. The same antibody could also have the potential to be used in other regions of the central nervous system.

“This paves the way for more interesting basic research into 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 Communication.

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