Skip to main content

Advertisement

Advertisement

Researchers develop mouse that carries human immune cells

SINGAPORE — Drug development for dengue — a disease whose treatment has eluded scientists for decades — has long been an expensive and lengthy process, as drugs that worked well in the laboratory and on animals often failed when tested on humans, due to the differences between animal and human cells.

SINGAPORE — Drug development for dengue — a disease whose treatment has eluded scientists for decades — has long been an expensive and lengthy process, as drugs that worked well in the laboratory and on animals often failed when tested on humans, due to the differences between animal and human cells.

However this could change, thanks to the development of a mouse by researchers in Singapore which carries human immune cells. As dengue generally affects only humans and specifically uses immune cells for replication, the mice provide a more conducive model to test dengue therapeutics for people.

The study was published in the Journal of Virology last month by scientists from the Singapore-MIT Alliance for Research and Technology (SMART). The development comes as Singapore is poised to experience its second wave of the dengue epidemic this year — more than 15,900 individuals have been affected this year so far.

“With this humanised mouse model, we are able to study the dengue disease and drugs or vaccines in a human cell context, which is closer to what we’ll see in real humans,” said Dr Aishwarya Sridharan, lead author of the study, at a media briefing today (Sept 11).

Professor Jianzhu Chen, director of immunology at MIT and SMART lead investigator of infectious diseases, pointed out that previously, “70 per cent of drugs in trial fail at the Phase I and II human trial stages, either because they are too toxic or ineffective”.

Yet, the drugs had been tested successfully in the laboratory and animal settings, suggesting a gap between these testing environments and the actual human body environment, he said.

The “humanised mouse” will service as a better indicator of how effective a potential drug could be, before they are tested on people at a clinical trial. This will lower costs and development time as less resources are wasted on drugs that are less likely to succeed, Prof Chen said. Currently, drugs take an average of 10 to 12 years to develop,

The researchers took mice with a genetic mutation that prevents them from producing their own immune cells, and transplanted human fetal liver stem cells into them. They then infected the humanised mice with the dengue virus.

The mice were found to display four key symptoms of dengue infection in humans — in particular, a drop in blood platelet count, a first in the world. This led to researchers identifying the cause of the drop as a disruption in platelet production in the bone marrow.

With this finding, scientists can now proceed to identify potential drugs to counter or prevent the symptom, which is potentially life-threatening.

The researchers said they only conducted tests on the DEN-2 strain, the most prevalent in Singapore of the four dengue strains. The mice are patented and available for testing, and the team is currently in talks with some companies to begin testing potential therapeutics. Some 300 humanised mice have been bred so far.

“Basically, they are living test tubes,” Prof Chen said.

Read more of the latest in

Advertisement

Advertisement

Stay in the know. Anytime. Anywhere.

Subscribe to get daily news updates, insights and must reads delivered straight to your inbox.

By clicking subscribe, I agree for my personal data to be used to send me TODAY newsletters, promotional offers and for research and analysis.