A dog food additive may prevent the disabling effects of chemotherapy, according to new research from Johns Hopkins University. The findings, published today in the Annals of Neurology, offer a possible solution for future chemotherapy patients who may suffer from long-lasting nerve damage after treatment with the chemo-agent Taxol (paclitaxel).
Taxol, approved by the Food and Drug Administration in 1992, is one of the most successful cancer drugs in history. Proven highly effective against ovarian, lung, and breast cancer, the drug’s global revenues in 2006 were an estimated $3.7 billion. However, the drug has a dark legacy of causing permanent neurological side-effects in some patients, including balance problems, tingling, burning, and muscle weakness.
"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," remarked lead author Dr. Ahmet Höke, a professor of neurology and neuroscience at the Johns Hopkins University School of Medicine.
Dr. Höke and his team went searching for a compound that could be given to patients prior to chemotherapy to block Taxol-related neuropathy. A similar strategy has been used for years to prevent nausea with medications like Anzemet or the recently approved anti-nausea patch, Sancuso.
To track down a candidate, the researchers exposed nerve cells growing in different dishes to a panel of 2,000 drug candidates. The cells were subsequently given Taxol, which normally causes them to degenerate, but one compound showed exceptional protection against the chemotherapy. This standout was ethoxyquin, an antioxidant preservative commonly found in dog food, that is approved by the Food and Drug Administration (FDA). The compound is also used to keep pears and others foods fresh.
Ethoxyquin proved effective in follow-up experiments in mice, where Taxol cause nerve damage in their paws. Two-thirds of this injury was prevented when mice were given low doses on ethoxyquin prior to chemotherapy. The researchers estimate that if this dosage was scaled up for humans, it would be 20-30 times lower than what is found in dog food.
Further analysis showed that ethoxyquin interacts with three proteins — Hsp90, ataxin-2, and Sf3b2 — that are involved with cellular repair. The exact details remain murky, but Dr. Höke’s team plans to uncover them in the future research. In addition, they will determine if ethoxyquin or some derivative could help prevent peripheral neuropathy in chemo patients, which afflicts up to 30 million Americans, according to Dr. Höke.
"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," said Dr. Höke.
Source: Zhu J, Chen W, Mi R, Zhou C, Reed N, Höke A. Ethoxyquin Prevents Chemotherapy-Induced Neurotoxicity via Hsp90 Modulation. Annals of Neurology. 2013.