A drug approved in some countries to treat cholesterol can counteract hallmarks of a rare genetic disorder named DiGeorge syndrome, according to new experiments involving mice. The study delineates how this disease disrupts the function of mitochondria and leads to a breakdown in the blood-brain barrier, and suggests that the drug, named bezafibrate, could be translated into a new therapy. The blood-brain barrier acts as the guardian of the central nervous system, shielding it from foreign invaders and toxins. The brain relies on the blood-brain barrier to function properly, so defects in the barrier are closely linked to neurodevelopmental disorders and neurodegenerative conditions such as Alzheimer’s disease. In this study, Alexis Crockett and colleagues examined how the blood-brain barrier breaks down in DiGeorge syndrome (or 22qDS), a disease caused by a deletion in a group of genes. Patients with DiGeorge syndrome have a high risk of neurological conditions as well as schizophrenia, and there are few effective treatments. Using induced pluripotent stem cells, the team cultivated endothelial cells derived from four patients with DiGeorge syndrome. The cells displayed marked defects in their mitochondria, such as abnormally low production of ATP, which impacted their ability to maintain a barrier model in vitro. However, treatment with bezafibrate restored the function of mitochondria and the cells’ ability to form barriers. The drug had similar benefits in a mouse model of DiGeorge syndrome and also improved the rodents’ social functioning. “Together, our findings […] identify a potential therapeutic mechanism by which the [blood-brain barrier] may be targeted in these conditions,” Crockett et al. conclude.
