Scientists at Wake Forest School of Medicine Identify Anti-leprosy Drug as Potential Treatment for Multiple Myeloma

September 27, 2018

Multiple myeloma (MM) is a type of blood cancer that affects plasma cells in the bone. It is believed that approximately 100,000 Americans currently have the disease, according to the National Organization for Rare Disorders. 

Although several drugs are used to treat the disease, MM remains incurable, necessitating the development of new therapies. A research team, led by Mikhail A. Nikiforov, Ph.D., professor of cancer biology at Wake Forest School of Medicine, may have found a likely candidate.

Reported in the current issue of The Journal of Clinical Investigation, the scientists identified a drug currently used to treat leprosy and tuberculosis as a potential new therapy for MM patients.

Through a review of a virtual drug database, Nikiforov’s team identified clofazimine as a potent aryl hydrocarbon receptor (AHR) inhibitor and a suppressor of polyamine production. Recent studies had linked AHR activation with an increased risk of MM. And a separate study had found that polyamine levels were substantially elevated in patients with the disease, Nikiforov said.

To test the efficacy of the drug, the team conducted experiments in an animal model of the disease and in cell cultures. The team found that clofazimine was highly effective and comparable to bortezomib, a drug currently used to treat MM.

“In this study, we identified a previously unrecognized regulatory axis between AHR and polyamine metabolism and revealed that clofazimine acted as an inhibitor of AHR and is a potentially clinically relevant anti-multiple myeloma agent,” Nikiforov said.

In an accompanying commentary published in the journal, Robert A. Casero Jr., Ph.D., of Johns Hopkins School of Medicine, characterized this new finding as “intriguing and provides promise for moving such a strategy to the clinic.”

This work was supported by NIH grants CA220096, CA224434, CA193981 and CA190533; a Ruth L. Kirschstein National Research Service Award F32CA189622; NIH grants CA197996, 1F99CA21245501, R01AI100157 and R01CA121044; the Jennifer Linscott Tietgen Foundation; and in part by a National Cancer Institute Cancer Center Support Grant P30CA16056 to the Roswell Park Comprehensive Cancer Center, for the Clinical Data Network and the Animal Facility.

Co-authors are: Anna Bianchi-Smiraglia, Ph.D., Archis Bagati, Ph.D., Emily E. Fink, Ph.D., Hayley C. Affronti, Ph.D., Brittany C. Lipchick, Ph.D., Sudha Moparthy, B.A., Mark D. Long, B.A., Spencer R. Rosario, B.A., Shivana M. Lightman, B.A., Kalyana Moparthy, B.A., David W. Wolff, Ph.D., Dong Hyun Yun, B.A., Zhannan Han, B.A., Anthony Polechetti, B.A., Matthew V. Roll, B.A., Ilya I. Gitlin, Ph.D., Katerina I. Leonova, Ph.D., Aryn M. Rowsam, B.A., Eugene S. Kandel, Ph.D., Andrei V. Gudkov, Ph.D., Kelvin P. Lee, M.D., Dominic J. Smiraglia, Ph.D., of Roswell Park Comprehensive Cancer Center in Buffalo, New York; and P. Leif Bergsagel, M.D., of Comprehensive Cancer Center of the Mayo Clinic in Scottsdale, Arizona.

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