New Molecule Shows Promise In Repairing Blood-Brain Barrier Damage

You may not know it, but there’s a special defender in our bodies called the blood-brain barrier. It protects our brain from harmful substances. However, when this barrier is compromised, various conditions can arise. For example, cancer cells can enter and form tumors, or multiple sclerosis can occur when immune cells attack the protective layer of nerves in the brain. That’s why scientists have been eager to find ways to repair this crucial barrier, and a recent paper has made exciting progress in that direction.

A team of researchers, led by Dr. Calvin Kuo at Stanford Medical has uncovered a potential treatment that could restore the normal function of the blood-brain barrier. In their study, they explored a communication pathway called WNT signaling, which helps maintain the barrier’s integrity by promoting cell-to-cell communication in the lining of brain blood vessels.

“We hope this will be a first step toward developing a new generation of drugs that can repair the blood-brain barrier, using a very different strategy and molecular target than current medications,” Kuo said in a media release.

The researchers focused on a protein receptor called frizzled, which initiates the WNT pathway. By selectively targeting cells lining the brain’s blood vessels, they developed molecules that activate the frizzled receptor and enhance WNT signaling. One such molecule, called L6-F4-2, proved to be 100 times more efficient than previous binders in activating the pathway.

To test the effectiveness of L6-F4-2, the scientists turned to Norrie disease, a genetic condition that causes a leaky blood-retinal barrier, similar to the blood-brain barrier but in the eye. In mice with Norrie disease, they replaced the missing protein responsible for activating the frizzled receptor with L6-F4-2. The results were promising, as the blood-retinal layer was restored, with denser and less leaky blood vessels.

The researchers then investigated the effects of L6-F4-2 on ischemic stroke, a condition where damage occurs to blood vessels and the blood-brain barrier, leading to the leakage of fluid, blood, and inflammatory proteins into the brain. In mice with induced strokes, L6-F4-2 reduced the severity of the stroke, improved survival rates, and reversed the leakiness of brain blood vessels.

This breakthrough discovery indicates that drugs activating frizzled receptors and the WNT signaling pathway could restore the blood-brain barrier in mice. Those drugs could potentially help treat diseases like Alzheimer’s, multiple sclerosis, and brain tumors, as many of these conditions are linked to blood-brain barrier dysfunction.

The team hopes that this research will pave the way for a new generation of drugs capable of repairing the blood-brain barrier, offering an innovative strategy and molecular target for future medications. Restoring the strength of the blood-brain barrier could be a significant step toward better treatments and improved outcomes for a range of neurological disorders.

The paper is published in the journal Nature Communications.

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