An innovative approach to treating brain diseases
An impressive number of brain pathologies are closely linked to major cerebrovascular defects, which are currently impossible to treat due to a lack of drugs.
By studying the proteins controlling the formation of these vessels during embryonic life, Benoit Vanhollebeke (WELBIO-ULB) and his team believe they can identify targets with promising therapeutic potential. The evidence is that by developing molecules targeting the Gpr124/Reck membrane complex, whose role was first revealed in a neurodevelopmental context, the researchers have succeeded in slowing down the progression of glioblastoma, the most common primary adult brain cancer, in mice, and reducing the lesions following a stroke.
The same team had previously published on the mechanistic characterisation of the therapeutic target in Science. This new study establishes its therapeutic potential in mice. When the target is activated, dysfunctional cerebral blood vessels made too permeable by the pathology regain their original functionality; they recover a set of cellular and molecular characteristics that strongly limit exchanges between blood and neural tissue and are collectively called the blood-brain barrier. The brain is thus again protected from toxic components circulating in the blood, and the progression of pathologies is slowed.
"One of the most fascinating aspects of this study is the level of specificity with which pathological brain vessels respond to this experimental treatment. Inspired by the natural developmental process, we have designed a new class of molecules that are able to reach their therapeutic target efficiently, while remaining completely inert for healthy vessels and other tissues of the body. On a fundamental basis, this level of specificity seemed a priori out of reach," explains Benoit Vanhollebeke.
To build on this, the researchers from the Neurovascular Signalling Laboratory now want to explore other experimental models of brain pathologies that could potentially benefit from their approach.
Benoit Vanhollebeke and the ULB have created the spin-off company NeuVasQ Biotechnologies, which, with the support of a consortium of public and private investors, aims to bring this type of neurovascular treatment to the bedside.
Reference : Science, 2022, 375 DOI: 10.1126/science.abm4459
Source : Press Release ULB
Photo by : Laure Twyffels