UAB sleuths find drug candidate against COVID-19

UAB sleuths find drug candidate against COVID-19
UAB researchers have joined consortiums across the country in the search for drugs to fight the novel coronavirus, or COVID-19. Researchers are using an arsenal of drugs and medicines, some repurposed. For example, the efficacy of the prostate-cancer-fighting drug degarelix is being tested as a method of preventing COVID-19 infection in men's lung tissue as part of a double-blind study. (UAB)

The medical detectives at the Hugh Kaul Precision Medicine Institute at the University of Alabama at Birmingham helped find a potential drug to treat COVID-19. Degarelix, a Food and Drug Administration-approved drug for prostate cancer, is now undergoing a clinical trial to see if it can prevent the SARS-CoV-2 virus from entering lung tissue.

The double-blind randomized controlled trial of degarelix is being run by the United States Department of Veterans Affairs. The trial will compare degarelix (trade name Firmagon) to a placebo for improving the clinical outcomes of nearly 200 male veterans who have been hospitalized with COVID-19.

“In January, as word of this new virus began to circulate, we started employing our resources to see what we could learn about the virus, and any potential means to counteract it,” said Matt Might, Ph.D., director of the Precision Medicine Institute in the School of Medicine at UAB. “One of our strengths is to use our trained analysts and artificial intelligence tools to look for FDA-approved drugs that might also have activity against a new target, such as the SARS-CoV-2 virus.”

The team is skilled at finding FDA-approved drugs that might also have activity against a new target. (UAB)

With advanced artificial intelligence and computational genomics techniques, Might’s team began to ask questions. What are the symptoms of this new disease? What medications do we already have that block or suppress the various symptoms? What do we know of the virus itself? What molecular targets can we hit with existing drugs? As the answers filtered in, one possible strategy rose to the top: androgen deprivation therapy and, with that, the highly potent degarelix.

Androgens are hormones, such as testosterone, that regulate the development and maintenance of male characteristics. Degarelix is used in androgen deprivation therapy for prostate cancer to reduce the level of androgen hormones.

“I reached out to a number of scientists, including the head of research for the VA, Dr. Rachel Ramoni, to discuss degarelix,” Might said. “One of my colleagues at Columbia University, David Goldstein, had also reached a similar conclusion via different means on the possible efficacy of androgen deprivation as a strategy. The more we investigated, the more it seemed like a good candidate.”

In prostate cancer, degarelix works by rapidly, but temporarily, suppressing the body’s production of male hormones, which can fuel the growth of prostate cancer. Might and Goldstein found lab evidence suggesting male hormones trigger the production of a protein called TMPRSS2 on lung tissue. The virus that causes COVID-19 relies on TMPRSS2 to enter lung tissues.

After further research suggested degarelix would have activity against SARS-CoV-2, the VA launched the clinical trial on May 15. Patients will be administered only one dose of the drug that will last 28 days. Any side effects of degarelix are thus expected to be temporary.

By temporarily lowering male hormone levels, researchers believe they can reduce the production of TMPRSS2 in lung tissue and thus prevent the virus from penetrating lung cells. Hormone levels will return to normal at the end of treatment.

The study is not suitable for female veterans. Existing evidence shows degarelix may have the opposite effect in the female body by increasing TMPRSS2 production, thus worsening the severity of COVID-19 symptoms.

“Degarelix is one of over 200 drug compounds that the Precision Medicine Institute is investigating in UAB labs,” Might said. “Many of these either block a target that has been identified in the COVID-19 pathway or manage a symptom of the disease, giving us reason to initiate further tests.”

The West Los Angeles VA Medical Center is leading the trial. The study also involves VA medical centers in New York (Brooklyn and Manhattan) and Washington state (Puget Sound), leveraging the Prostate Cancer Foundation/VA network of centers of excellence. The University of California-Los Angeles is involved in the analysis of research specimens, but not the clinical element of the study.

VA researchers expect to complete the trial in about four months. For more information, visit research.va.gov.

This story originally appeared on the University of Alabama at Birmingham’s UAB News website.

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