A recent study by researchers at Mount Sinai Hospital and its School of Medicine has found that an inexpensive and widely available therapy targeting inflammatory genes reduces morbidity and mortality in mice infected with the SARS-CoV-2 virus . The study results were published in the journal Cell .
The therapy, called topotecan (TPT), inhibited the expression of inflammatory genes in the lungs of mice for up to four days after infection.
“So far, in preclinical models of SARS-CoV-2, no therapies—antiviral, antibody, or plasma—have been shown to reduce the disease burden of SARS-CoV-2 when administered more than one day after infection,” said Ivan Marazzi, lead author of the study. “This is a big problem because people who have severe COVID-19 and are hospitalized often don’t show symptoms until many days after infection.”
For the study, the researchers expanded on previous work they had done that found that inhibiting the activation of inflammatory genes could help prevent animal deaths from viral and bacterial infections.
The team discovered that many anti-inflammatory therapies were not as effective as TPT because they only target a single inflammatory mediator, such as IL6 or IL1.
"The fact is that a multitude of inflammatory genes and signaling pathways become dysregulated during a SARS-CoV-2 infection," said Jessica Sook Yuin Ho, lead author of the study. "We can dampen the expression of inflammatory genes in animal models, regardless of the gene or pathway that is activated."
The team plans to conduct future research to evaluate the safety and efficacy of treating humans with TPT for COVID-19 at several sites around the world, including India and Singapore.
“The findings of our work suggest that repurposing a topoisomerase 1 inhibitor could be a valuable global strategy for treating severe cases of COVID-19,” said Marazzi. “Particularly attractive is the fact that TPT is already FDA-approved and its derivatives are inexpensive, with generic formulations available worldwide. This makes these drugs readily accessible and available for immediate use in both developing and developed countries around the globe.”