A new drug targeting inflammation in the brain has been shown to bolster the blood-brain barrier in mice, pioneering a potential shift in the fight against neurodegenerative diseases like Alzheimer’s.
“Finding [the drug] blocks brain inflammation and protects the blood-brain barrier was an exciting new discovery,” says pathologist Sanford Markowitz from Case Western Reserve University (CWRU).
What’s more, the researchers note that amyloid levels – the abnormally clumping proteins traditionally thought to play a role in the progress of Alzheimer’s – remained the same. This suggests the new treatment, focusing on an immune protein called 15-PGDH, targets a completely different physiological pathway than many existing medications.
“This is important because the most recently approved Alzheimer’s drugs focus only on removing amyloid and, unfortunately, don’t work very well and have risky side effects,” explains Markowitz. “Inhibiting 15-PGDH thus offers a completely new approach for Alzheimer’s disease treatment.”
The blood-brain barrier is a layer of tissue that any substance entering the brain via the blood must pass through. When intact, the barrier filters out potential dangers such as toxins, bacteria, and viruses.
Traumatic brain injury can damage this barrier, increasing risks to brain cells. Such blood-brain barrier deterioration has also been identified as a possible early indicator of dementias like Alzheimer’s.
By investigating the molecules active within the blood-brain barrier cells, CWRU physiologist Yeojung Koh and colleagues were able to identify that the immune enzyme 15-PGDH was elevated in both mice and humans with neurodegeneration arising from age, injury, or disease.
In response, the researchers developed SW033291; a compound that can block the enzyme’s activity. The medication was found to successfully protect the blood-brain barrier in mice and prevent cognitive impairment even after traumatic brain injury.
“In these mouse models treated with the drug, the blood-brain barrier remained completely undamaged,” says neuroscientist Andrew Pieper, also from CWRU. “The brains didn’t undergo neurodegeneration and, most importantly, cognition and memory capacity were completely preserved.”
With almost 10 million new global cases of dementia yearly, an increasing number of people face cognitive decline, either personally or in loved ones. And despite decades of research, treatment outcomes remain unclear. Exploring new tactics like this is essential to improving lives, but there’s still a long way to go.
“Our findings establish 15-PGDH as a guardian of blood-brain barrier integrity… and a compelling target for protection from neurodegenerative disease,” Koh and team write in their paper.
This research was published in PNAS.
