Four out of five cancer patients taking the chemotherapy drug Taxol suffer from peripheral neuropathy, painful nerve damage in their hands and feet. Half of those people recover from the damage, but for the rest, debilitating pain, numbness, and tingling remain for the rest of their lives.
Researchers at Johns Hopkins have discovered that a chemical commonly used as a dog food preservative may prevent peripheral neuropathy. Working with cells in test tubes and in mice, Dr. Ahmet Höke and his team at the Johns Hopkins University School of Medicine found that the antioxidant ethoxyquin, a preservative approved by the Food and Drug Administration, was shown to bind to certain cell proteins in a way that limits their exposure to the damaging effects of Taxol.
The hope, they say, is to build on the protective effect of ethoxyquin's chemistry and develop a drug that could be given to cancer patients before taking Taxol, in much the same way that anti-nausea medication is given to stave off the nausea that commonly accompanies chemotherapy.
"Millions of people with breast cancer, ovarian cancer, and other solid tumors get Taxol to treat their cancer and 80 percent of them will get peripheral neuropathy as a result," says Höke, a professor of neurology and neuroscience at the School of Medicine and director of the Neuromuscular Division. "They're living longer thanks to the chemotherapy, but they are often miserable. Our goal is to prevent them from getting neuropathy in the first place."
A report on Höke's research is published online in the Annals of Neurology.
Höke and his team knew from previous experiments that adding Taxol to a nerve cell line growing in a petri dish would cause neurodegeneration. In a series of experiments, they set out to hunt for compounds that might interrupt the degenerative process by adding Taxol to nerve cells along with some 2,000 chemicals—one at a time —to see which, if any, could do that.
Ethoxyquin did so, Höke says, apparently by making the cells resistant to the toxic effects of the Taxol.
Once they identified ethoxyquin's effects, they gave intravenous Taxol to mice, and saw nerves in their paws degenerate in a couple of weeks. But when they gave ethoxyquin to the mice at the same time as the Taxol, it prevented two-thirds of the nerve degeneration, which Höke says would have a big impact on quality of life if the same effects were to occur in humans.
Twenty to 30 million Americans suffer from peripheral neuropathy. Höke says it's a "huge public health issue" that doesn't get much attention because it is not fatal.
Höke's team is hoping to conduct safety studies with ethoxyquin in animals in advance of possible testing in people. He says that while too much ethoxyquin is thought to be potentially harmful to dogs, the needed dose for humans would likely be 20-to-30-fold lower than what is found in dog food. Ethoxyquin was developed in the 1950s as an antioxidant, a compound to prevent pears and other foods from becoming discolored and spoiling.