Emory Report

September 8, 1998

 Volume 51, No. 3

Scientists uncover possible cancer therapy in cough syrup

Attending a conference in France, Harish Joshi, associate professor of cell biology, grabbed a seat in the back of the room and watched a slightly out-of-focus slide presentation on the structures of various drugs used in microtubule research. Microtubules are structures involved in cell division, and many of the slides showed drugs currently used in chemotherapy as they interrupt microtubule dynamics and stop cancer cells from dividing.

Not able to view the slides too well, "I was just looking at the general structure of the compounds, and I felt that there was a common motif among those microtubule drugs," Joshi recalled. After returning to Emory, he had graduate student Keqiang Ye investigate drugs with structures similar to those in the anti-cancer medicines.

The researchers then tested the drugs Ye had found for their ability to halt cell division in a cancer cell line cultured in flasks. The best performing drug was noscapine, a compound derived from opium and currently used as an active ingredient in cough medicines produced in Europe and Asia.

Joshi then collaborated with Professor of Ophthalmology and Pathology Judith Kapp in a study of mice with cancerous tumors. The animals were injected with noscapine to see if the drug would kill the tumors or at least slow their growth. The study was successful, even beyond what the researchers had expected.

Current anti-cancer drugs such as taxol are toxic not only to cancer cells but to healthy cells as well. While targeting tumors, these drugs also kill off other fast-growing cells such hair follicles, the lining of the intestines and immune cells, creating hair loss, nausea or susceptibility to infection.

Noscapine appears to act differently. "This drug is relatively mild in terms of its effect on the immune system," said Kapp. Because of this, scientists and manufacturers instantly took notice when Joshi and Kapp's findings were published along with augmenting studies from other Emory researchers.

"Immediately after this article was published, we received numerous calls from industry," said Kevin Lei of the Office of Technology Transfer. Hoping to secure a sponsor to fund clinical trials on cancer patients, the researchers would like to conduct Phase I and II trials to examine noscapine's safety and further document the drug's ability to fight cancer. If trials like these prove successful, drugs usually are submitted to the FDA for approval.

While that all seems easy, it hasn't been smooth sailing for Emory.

The University has submitted a patent on noscapine, but because the drug is already used in cough medicine, the patent only covers its use only as an anti-cancer drug. Any company investing heavily in clinical trials faces a gamble in its ability to recoup capital, since it would not retain sole rights to the drug. This uncertainty has scared off larger companies that usually manufacture synthetic drugs, but Emory officials remain cautiously optimistic.

"The best thing [noscapine] has going for it is that it's been used by people for a very long time, so we know that it's relatively safe-and that's a very big step," said Dennis Liotta, vice president for research. Emory also is looking to develop additional noscapine analogs-chemically synthesized changes to the drug's structure, Liotta said. These slight changes might prove even more effective in stopping cancer, and since they would be man-made, the new compounds could be patented.

Throughout this turn of events, Joshi and other researchers here have continued studying noscapine and will soon publish another paper. And while Joshi remains somewhat stunned at all the attention he has received from CNN and other press sources, he remains very grounded in the seriousness of his work. "There are patients out there who are so desperate," said Joshi, who receives daily phone calls from cancer patients. His hope remains that a slightly out-of-focus slide might have provided the genesis for a cancer cure.

--Paul Thacker

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