Scientists at LMU University Hospital in Munich have discovered new details about how diseases of the brain’s tiny blood vessels develop—and they’ve identified a drug that could help fix the problem.
This condition, known as cerebral small vessel disease, affects the brain’s smallest blood vessels and can lead to strokes, bleeding in the brain, and even dementia. It’s one of the top causes of long-term disability and death, but until now, researchers didn’t fully understand what caused it.
The brain’s small vessels are difficult to study directly in humans. They are tiny and hidden deep in the brain, making it hard for doctors and scientists to see what goes wrong. There also haven’t been many good lab models to study this disease in detail.
To solve this, the research team created special mice in which certain cells lining the blood vessels—called endothelial cells—could no longer make a protein due to a missing gene called Foxf2.
These endothelial cells form the inside wall of blood vessels and play a big role in keeping them healthy. In the mice without the Foxf2 gene, these cells started to break down, and the barrier that protects the brain from harmful substances—called the blood–brain barrier—was damaged.
The loss of Foxf2 clearly played a major role in the disease. This gene helps control many other genes. One of those is called Tie2, which is part of a pathway that keeps blood vessels stable and healthy. If Tie2 is not active, inflammation can build up, which makes blood vessels weaker and raises the chances of stroke and dementia.
The scientists also looked at human cells and confirmed the same problems. Working with another expert, Professor Dominik Paquet, the team showed that the same changes seen in mice also happened in human cells, which makes the findings more reliable.
They didn’t stop there. Using a drug called AKB-9778, which can turn on the Tie2 gene, the team tried to repair the damaged blood vessels in the mice. The results were impressive.
After treatment, the Tie2 pathway was working again, and the blood vessels started to heal. This could mean that AKB-9778 might help lower the risk of both stroke and dementia by restoring brain vessel function.
Unfortunately, the drug is currently being tested for other diseases, so it’s not yet available for use in small vessel disease. But the team is now searching for similar drugs that could be tested in people in the future.
In conclusion, this study shows that the Foxf2 gene and the Tie2 pathway are key to understanding and treating cerebral small vessel disease.
The research opens the door to new therapies that could prevent strokes and protect the brain from dementia. With more work, these findings could lead to real treatments for people at risk of these serious conditions.
If you care about stroke, please read studies about how to eat to prevent stroke, and diets high in flavonoids could help reduce stroke risk.
For more health information, please see recent studies about how Mediterranean diet could protect your brain health, and wild blueberries can benefit your heart and brain.
The study is published in Nature Neuroscience.
Copyright © 2025 Knowridge Science Report. All rights reserved.
