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Medical Research

Another Purpose for A Lifesaving Cancer Drug

Researchers at the Icahn School of Medicine at Mount Sinai say that tiny doses of a cancer drug may stop the raging, uncontrollable immune response to infection that leads to sepsis and kills up to 500,000 people a year in the U.S. 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 I (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 — deadly infections often acquired in hospital by patients with a weak immune system — but also new and brutal assaults on human immunity such as novel influenza strains and pandemics of Ebola and other singular infections, says the study’s senior investigator, Ivan Marazzi, PhD, an Assistant Professor of Microbiology at the Icahn School of Medicine.

“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,” says 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 says. “This drug appears to offer that life-saving correction.”

Sepsis is caused by an excessive host response to infection, which in turn leads to multiple organ failure and death. With an overall mortality rate between 20 and 50%, sepsis is the tenth leading cause of death in the U.S. — it kills more people than do HIV and breast cancer.

“To date there has been no targeted treatment for sepsis, or for other infections that promote this inflammatory storm,” says Marazzi. “Such treatment is desperately needed.”

For example, sepsis is a leading cause of death in infants and children, he says. “Septic shock and lung destruction can occur when a child is suffering from a pneumonia caused by co-infection with a virus and a bacteria even when antibiotic therapy is being used. The elderly are also especially vulnerable to sepsis.”

Following a challenge from the National Institutes of Health to repurpose existing drugs for new uses, the research team used a simple cellular screen to find candidate drugs that could tamp down rampant inflammation.

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