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08 May 2017

A therapy that targets the gut could hold the key to preventing graft versus host disease after stem cell transplant, according to a German study.

The researchers have developed a therapy which they believe will tackle the source of GvHD in the gut.

They believe the disease starts in the gut and the therapy aims to restore epithelial cells in this organ damaged by radiotherapy and chemotherapy.

According to this theory, the damage to the gut leads to the activation of aggressive T-cells in the donated stem cells.

Reporting in Science Translational Medicine, the researchers say that in a mouse model their treatment approach appeared not to reduce the effect of leukaemia therapy "to a measurable degree."

Their treatment involved administering triphosphate-RNA (3pRNA) 24 hours after radiotherapy and chemotherapy. This stimulates the RIG-I signal pathway, leading to repair of epithelial cells.

The researchers say this seemed to protect the animals from lethal GvHD.

The research involved the Technical University of Munich, Germany, working with the Memorial Sloan Kettering Cancer Center, New York, USA.

Researcher Dr Hendrik Poeck said: 'Our study shows that regenerative processes can also be triggered through selective activation of these signal paths.

'It thus appears quite possible that these selective agonists will be administered in the future to patients who are candidates for allogeneic stem cell transplants. However, further studies will be needed to learn how they actually work before applications in human medicine are possible.'


Source: RIG-I/MAVS and STING signaling promote gut integrity during irradiation- and immune-mediated tissue injury.

Science Translational Medicine 19 April 2017; doi: 10.1126/scitranslmed.aag2513