New Prostate Cancer Drug Shows Promise against COVID-19
Researchers look into a drug called proxalutamide as a potential therapeutic for the coronavirus
At the outset of the COVID-19 pandemic, men appeared to suffer higher rates of severe illness and death, leading researchers to suspect a link between androgen receptors and SARS-CoV-2 viral infection.
This observation spurred Michigan Medicine researchers to look into a drug in development to treat prostate cancer—called proxalutamide, which works by blocking an enzyme, TMPRSS2 (transmembrane serine protease 2) that is regulated by androgen receptors—as a potential therapeutic for COVID-19. The team recently published their study in PNAS.
“We were already studying TMPRSS2 as part of the key gene driver of over 50 percent of prostate cancer, so it made sense to look at it as TMPRSS2 is an important host factor for SARS-CoV2 to enter cells in the lung,” said Arul Chinnaiyan, MD, PhD, director of the Michigan Center for Translational Pathology and the S.P. Hicks Endowed Professor of Pathology.
The team added proxalutamide to cells infected with SARS-CoV-2 to monitor its ability to block viral entry. The compound works by binding to androgen receptors, inhibiting levels of TMPRSS2 and ACE2, and blocking infection.
What’s more, proxalutamide worked better than other prostate cancer drugs against multiple variants of SARS-CoV-2 due to its ability to break down the androgen receptor. Additionally, proxalutamide, when combined with the FDA-approved drug for COVID-19, remdesivir, was able to fully block infection.
“This discovery underscores the utility of testing existing drugs for new applications that can be rapidly evaluated in humans to shorten the timeline from discovery to clinical evaluation," said Jonathan Sexton, PhD, assistant professor of internal medicine at the University of Michigan (U-M) Medical School and assistant professor of medicinal chemistry in the College of Pharmacy, who is also director of the U-M Center for Drug Repurposing.
Buoyed by their in vitro results, the team looked to see whether the compound could stop the so-called cytokine storm, or severe inflammatory response, caused by SARS-CoV-2 infection. Using a mouse model, they demonstrated that the drug reduced inflammation and cell death in the lungs of mice and reduced mortality. “The thought is that proxalutamide could work as a combined therapy with remdesivir, hitting the virus from multiple angles, much as combination therapy works so well for HIV infection.”
The drug is currently in Phase 3 clinical trials for prostate cancer and early clinical trials for COVID-19.
- This press release was originally published on the Michigan Medicine website