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HUN-REN BRC researchers’ findings could revolutionise brain-active drug testing

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A recent study by researchers at the HUN-REN Biological Research Centre (HUN-REN BRC) in Szeged could bring a breakthrough in the investigation of drug delivery to the brain. In an international project led by Professor Mária Deli (Biological Barriers Research Group), they examined how the so-called blood-brain barrier, a unique protective system in our brain blood vessels, is formed. The study was published in the prestigious journal PNAS.

Deli Mária

Due to the unique structure of brain capillaries, most drugs are unable to penetrate from the bloodstream into the brain tissue to exert their effects. This poses a major obstacle in the treatment of neurological diseases such as Alzheimer's or epilepsy. Predicting whether a particular compound will be able to cross the human blood-brain barrier at an early stage in drug research is crucial, with current cell culture models not being suitable for this purpose.

A recent publication from researchers in Szeged, Hungary, reports on the hitherto unknown interaction of three signalling pathways involved in the development of the blood-brain barrier. To target the pathways together, the authors have created a small molecule cocktail, cARLA, which is better than ever before at engineering blood-brain barrier properties in blood vessel-forming endothelial cells.

In their recent publication, HUN-REN BRC researchers report on the previously unknown interaction of three signalling pathways involved in the development of the blood-brain barrier. To target these pathways simultaneously, they have developed a small molecule cocktail named cARLA, which allows for the most robust induction of blood-brain barrier properties in blood vessel-forming endothelial cells to date.

blood-brain barrier

Using small molecule cocktails, a blood-brain barrier model suitable for drug testing can be obtained.

"The novel method allows the generation of significantly more reliable blood-brain barrier models from human stem cells than ever before. These models can contribute to a more precise understanding of the physiological and pathological processes in brain capillaries and may be suitable for studying the brain penetration of drugs and drug carriers," summarises Gergő Porkoláb, a PhD student at HUN-REN BRC and lead author of the study.