Ebola-on-a-chip: Leiden scientists against a fatal virus
Although Ebola is a virus with significant fatality rates, we still lack effective countermeasures to battle it. To change this, Alireza Mashaghi and his colleagues from the Leiden Academic Centre for Drug Research have successfully developed an organ-on-a-chip model that imitates the most dangerous symptoms of the disease. This new chip is used to test new drug candidates. The first results are promising and published in iScience.
The Ebola epidemic in West Africa (2014-2016) was a health crisis of great magnitude and impact, causing more than 11,000 deaths and destabilising multiple countries. Currently, the World Health Organization and African countries are struggling to contain a new large outbreak in Africa, which has already led to hundreds of deaths. Despite supportive care, more than 50 per cent of the patients die. ‘We still have no drug for the Ebola virus,’ says Mashaghi. ‘This is partly because animal models do not represent the human disease sufficiently. Furthermore, animal studies are ethically undesirable.’
Therefore, he and his colleagues invented an organ-on-a-chip model, which mimics the hemorrhagic shock syndrome. This dangerous syndrome is the hallmark of Ebola and the main cause of death in patients. The researchers use the chip to test new drug candidates.
Hemorrhagic shock occurs when the body shuts down to a large amount of blood loss. In Ebola, this blood loss is caused by internal and external bleedings due to the fact that the virus increases the permeability of the vessels. The subsequent blood volume loss in patients leads to organ failure and a great drop in their blood pressure, which is called a shock.
‘The chip we created mimics what happens during such a shock. It is composed of a human microvessel on a glass chip that interfaces a tissue model’, tells Mashaghi. ‘This interface is leak-tight, so no blood could leak out of the vessel at the interface. But, when virus particles circulate in the blood, they affect this interface and disrupt it, so the blood starts leaking through.’
The scientists used the chip to test two new drug candidates. ‘Basically, one drug directly acts on the mechanical elements of the cells. The other blocks the biochemical reactions that are turned on by the virus and eventually lead to changes in the mechanical elements and cell-cell junctions’, tells Mashaghi. ‘The candidate drugs that we tested turned out to be highly effective on our chips. They completely halted the Ebola effect on the vessels!’
The chip is the first model of its kind. So far, there has been no chip-based model for any viral hemorrhagic disease. This family of diseases includes Ebola, Lassa, Dengue and many others Mashaghi: ‘Albeit with differing mechanisms, these diseases are all typically characterised by the same shock syndrome. Our chip could be adapted and generically used to study all these diseases and to develop drugs that target these devastating conditions. We are currently exploring the potentials.’
Junaid, A.; Tang, H.; Reeuwijk, A.; Abouleila, Y.; Wuelfroth, P.; van Duinen, V.; Stam, W.; Zonneveld, A.; Hankemeier, T. and Mashaghi, A. (2020). Ebola Hemorrhagic Shock Syndrome-on-a-Chip. iScience.