Researchers at the Icahn School of Medicine at Mount Sinai claim that tiny doses of a cancer drug may stop the immune response to infection that leads to sepsis.
The new drug treatment may also benefit millions of people worldwide who are affected by infections and pandemics.
Their study reported in Science, demonstrates in both cells and animals that a small dose of Topoisomerase 1 (Top 1) inhibitor can dampen an acute inflammatory reaction to infection while still allowing the body’s protective defense to take place. The title of the study is ‘Topoisomerase 1 inhibition suppresses the transcriptional activation of innate immune responses and protects against inflammation-induced death.’
The treatment may help control not only sepsis but also new assaults on human immunity such as novel influenza strains and pandemics of Ebola and other singular infections, said the study’s senior investigator, Ivan Marazzi, PhD, an assistant professor of microbiology at the Icahn School of Medicine at Mount Sinai.
“Our results suggest that a therapy based on Top 1 inhibition could save millions of people affected by sepsis, pandemics, and many congenital deficiencies associated with acute inflammatory episodes – what is known as a cytokine, or inflammatory, storm,” said Marazzi.
“These storms occur because the body does not know how to adjust the appropriate level of inflammation that is good enough to suppress an infection but doesn’t harm the body itself,” he explained. “This drug appears to offer that life-saving correction.”
The Mount Sinai team found that use of one to three doses of a Top 1 inhibitor that is 1/50th the strength of normal chemotherapy was enough to rescue 70% -90% of mice from an inflammatory storm death due to either acute bacterial infection, liver failure, or virus-bacteria co-infection. The treatment did not produce overt side effects. They also tested the inhibitor in cells infected with influenza, Ebola, and other viral and bacterial microbes that over-stimulate the immune system, and found the drug blunted a dangerous immune reaction.
“We observed a striking effect of Top-1 inhibitors on expression of pro-inflammatory molecules induced by Ebola virus infection. This study contributes our understanding of pathogenesis of Ebola virus disease and also suggests a direction to develop treatments,” said Alexander Bukreyev, PhD, professor in the Department of Pathology and Microbiology & Immunology at the Galveston National Laboratory at the University of Texas Medical Branch.
