New research on repairing blood-brain barrier leads to innovative approach to treating multiple brain diseases

Neurodegenerative diseases such as traumatic brain injury, stroke, brain tumor or Alzheimer's disease all involve dysfunction of a key player in protecting the brain, the blood-brain barrier (BBB)

An intact blood-brain barrier acts as a filter between blood and brain tissue, protecting the brain from toxic components in the blood circulation

A new study in the top academic journal Science shows an innovative approach to repairing the blood-brain barrier

Previous work has found that the early development and maintenance of the blood-brain barrier is regulated by two secreted protein molecules, Wnt7a and Wnt7b

A practical problem with this line of thinking, however, is how to improve specificity

To this end, the research team at the ULB Neuroscience Institute in Belgium developed a special engineered Wnt7a protein

▲ According to the special pattern of Wnt7a activating receptors on vascular epithelial cells, the researchers designed Wnt ligands that specifically target the blood-brain barrier (Image source: Reference [1]

Specifically, the engineered Wnt7a protein (Wnt7a K190A) differs from native Wnt7a by only one amino acid, but this mutation confers the ability to selectively bind the Gpr124/Reck complex

Using Xenopus laevis, zebrafish, neonatal mice and other animals as models, the researchers first verified that the mRNA encoding the Wnt7a K190A protein did not cause developmental abnormalities even if it was delivered to animals at high doses, providing a safe treatment for it.

Next, the researchers examined the therapeutic potential of Wnt7a K190A in mouse models of brain tumors and ischemic stroke

▲ Schematic diagram of the research on repairing the blood-brain barrier using the modified Wnt7a (Image source: Reference [1]; Credit: Illustration created with BioRender)

The experiments showed that mice transplanted with glioblastoma cells also had smaller tumors after restoring Wnt signaling in the vascular endothelium and the properties of the blood-brain barrier

At the end of the paper abstract, the researchers pointed out that this new type of blood-brain barrier therapy can restore the function of the blood-brain barrier by specifically regulating Wnt signaling, bringing potential new treatments for central nervous system diseases

References:

[1] Maud Martin et al.

[2] Andrew McMahon & Justin Ichida (2022) Repairing the blood-brain barrier.

[3] Method enables blood-brain barrier repair in neurological disorders.

(Original abridged)