Researchers at Johns Hopkins have discovered to their surprise that two drugs commonly used for treatment might be beneficial in treating other more serious disorders.

These researchers discovered that a drug commonly used to treat toenail fungus can also block angiogenesis, the growth of new blood vessels commonly seen in cancers. The drug, itraconazole, already is FDA approved for human use, which may fast-track its availability as an antiangiogenesis drug.

In mice induced to have excess blood vessel growth, treatment with itraconazole reduced blood vessel growth by 67 percent compared to placebo. "We were surprised, to say the least, that itraconazole popped up as a potential blocker of angiogenesis," says Jun O. Liu, Ph.D., professor of pharmacology. "We couldn't have predicted that an antifungal drug would have such a role."

In their search for antiangiogenesis drugs, the researchers worked with cells from human umbilical cords, a rich source of blood vessels, and exposed them to 2,400 existing drugs - including FDA- and foreign-approved drugs, as well as nonapproved drugs that had passed safety trials - to see which ones could stop the cells from dividing.

"The best outcome was to find an already approved drug that worked, and the fact that we did was very satisfying," says Liu.

While the researchers still must tease out exactly how itraconazole works to stop vessel growth, and test it in animals with cancer, they have high hopes for its use. "Itraconazole can be taken orally for fungal infection, and therefore oral delivery may work for angiogenesis as well," Liu notes.

Johns Hopkins researchers also have discovered that the same ingredient used in dandruff shampoos to fight the burning, itching and flaking on your head also can calm overexcited nerve cells inside your head, making it a potential treatment for seizures.

Epilepsy and other seizure disorders result when nerves excessively or inappropriately "fire" in the brain. The brain's "off" switches fail in part due to protein defects that prevent potassium from exiting nerve cells and calming them. "Channels that carry potassium," says Min Li, Ph.D., professor of neuroscience at Johns Hopkins, "must open on cue to make sure nerve cells only fire for defined periods of time."

One chemical that proved quite effective in improving channel recovery was zinc pyrithione (ZnPy), the active ingredient in many dandruff shampoos. Li explains that ZnPy has a shape that allows it to fit into the gate region of the channel protein and allow more potassium flow.

"Most drug discoveries uncover chemicals that stop things from working - it's a lot easier to close or block a door than open it," Li says. "But here we found a chemical that makes a defective protein work better. So now we have a chance to actually try to fix the causes of epilepsy, rather than traditionally circumventing them. Plus, this study really shows that we don't fully appreciate the biological roles of many familiar chemicals that surround us."

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