The drug tamoxifen appears to kill a fungus associated with a deadly brain infection that afflicts HIV/AIDS patients, according to a University of Rochester study published online today by mBio, the journal of the American Society for Microbiology.
The findings, by Damian J. Krysan, M.D., Ph.D., associate professor of Pediatrics and Microbiology and Immunology at the UR School of Medicine and Dentistry, point to an example of Rochester researchers looking to repurpose older drugs by discovering new applications for secondary properties of the drug. In this case, investigators found that tamoxifen can interfere with a protein, calmodulin, allowing it to kill the cryptocuccus germ. Making modifications to tamoxifen in the laboratory also boosted its ability to work as an anti-fungal.
Cryptococcus is responsible for about 1 million new infections and 620,000 annual deaths worldwide. It appears in the brain as either pneumonia or meningoencephalitis. No substantial improvements in treatment have occurred in a half-century.
Additional animal experiments are needed, Krysan said, before scientists can design clinical trials or develop new anti-cryptococcal drugs based on the tamoxifen findings. Meanwhile, a group of cancer researchers led by Mark Noble, Ph.D., professor of Biomedical Genetics at the University of Rochester, has shown with preclinical data that tamoxifen – which is usually prescribed to treat early-stage, less-aggressive breast cancer in premenopausal women – might also work for more aggressive, triple-negative disease, or on brain cancer.
Krysan's research was funded by the National Institute of Allergy and Infectious Disease.