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

03.06.2024 | by

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.

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

Photographer: Nyitrai Szilard

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.

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

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