In Biomaterials, DZNE researchers present a novel method for testing chemical agents that could help in the development of drugs against neurodegenerative diseases. This analytical technique allows to study in the laboratory whether new drug candidates have a realistic chance of reaching the brain.
To do this, a team led by Dr. Philip Denner and Dr. Eugenio Fava employs human stem cells and microcapillaries that mimic brain vessels of the so-called blood-brain barrier. The technique is specifically designed for anti-inflammatory agents.
3D-reconstruction of an artificial brain vessel by fluorescence microscopy. Each vessel consists of single endothelial cells (magenta) that are closely connected to each other by so called tight-junctions (turquoise).
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To prevent harmful substances or pathogens from entering the brain from the blood stream, the blood vessels of the brain are lined with so-called endothelial cells that form the blood-brain barrier. “You can think of this layer of cells as a filter designed to protect the brain from hazards. It’s like the situation at a high-security area that not everyone is allowed into,” explains Dr. Eugenio Fava, a researcher at DZNE’s Bonn site and head of “Core Research Facilities & Services”. “Drugs against brain diseases must therefore be tailored so that they can cross the blood-brain barrier and thus act in the brain.”
Permeability testing therefore play a central role in the development of drugs for treating brain diseases. Such analyses aim to identify promising substances in the laboratory long before clinical trials in humans occur. It is at this early stage of drug development that the method devised by the Bonn researchers comes into play. “We think that our approach recreates the blood-brain barrier better than many techniques currently in use. This enables more realistic predictions of drug uptake by the brain,” Fava says. “Our method is specifically tailored to anti-inflammatory agents. This is our focus, because in recent years, inflammatory processes were found to play a significant role in neurodegenerative diseases such as Alzheimer’s."
The DZNE researcher sees application potential for the new screening method both in science and in the pharmaceutical industry: “The use goes beyond permeability tests of pharmaceutical substances. Some brain diseases compromise the blood-brain barrier. With our model system, you can replicate and study such pathological processes at the boundary between the bloodstream and the brain.”
The method essentially involves two stages. First, the compound to be tested is passed in aqueous solution through a technical device that mimics the filtering function of the blood-brain barrier. Subsequently, a sample is taken from behind the filter and examined to determine whether the compound has passed through the barrier. For this, the extracted fluid is put on a cell culture of human white blood cells. “These immune cells serve as sensors,” explains molecular biologist Dr. Sven Fengler, who played a key role in developing the new screening method. “If the fluid derived from our filter apparatus contains anti-inflammatory substances, the immune response of the white blood cells will be reduced. If the compound is absent, there is no reduction of the immune response detectable.”
MEDICA-tradefair.com; Source: German Center for Neurodegenerative Diseases (DZNE)