An antioxidant added to dog food could reduce the side-effects of Taxol – a chemotherapy drug, new research from Johns Hopkins University School of Medicine has found.
Taxol is used to treat common cancers such as breast, ovarian and lung cancer, but 80% of patients using Taxol suffer a particular side-effect. This can manifest as pain, numbness, tingling, loss of co-ordination or weakness in the hands and feet due to nerve damage in a process called peripheral neuropathy. What’s worse - in some patients the neuropathy never wears off, so even after they have stopped using Taxol, the symptoms remain.
The pain caused by Taxol-induced neuropathy limits the dose of the drug doctors can use, limiting the effectiveness of the chemotherapy. In addition to cancer patients, peripheral neuropathy can affect people suffering from other diseases such as diabetes and HIV, and there are currently no treatments available to prevent it, highlighting a serious public health problem.
In a recent study published in Annals of Neurology, Ahmet Höke’s lab at Johns Hopkins, Baltimore discovered that ethoxyquin, an antioxidant used to prevent spoilage in dog food, can also be used to protect nerves from the damaging side-effects of Taxol.
The experiment tested a library of small molecules to see if they could protect nerve cells, grown in the lab, from damage. Three different toxins were used in the test, Taxol – the chemotherapy drug at the heart of the study, ddC - an HIV drug, and capsaicin – the molecule that makes chilli peppers hot. Using three toxins made sure the molecules tested were not inactivating the toxin (which is important for chemotherapy), but helping neurons resist damage.
The experiment showed ethoxyquin made the neurons resistant to Taxol’s toxic effects, and further testing in mice showed it prevented two thirds of nerve damage in their paws. If there was a similar effect in humans, doctors could potentially prescribe higher doses of Taxol, and patients would have less severe side-effects if given ethoxyquin at the same time.
As an antioxidant, a high dose of ethoxyquin could cause liver toxicity, but experiments have shown the effective dose to be 20-30 times lower than that found in dog food where it appears to have no negative effects. The next stage of the research is to move the molecule into safety and efficacy trials in animals and then humans, before it could eventually be licensed as a treatment to reduce peripheral neuropathy. If successful, ethoxyquin has the potential to reduce the incidence of neuropathy encountered both in cancer treatment and in other common diseases including diabetes and HIV.
Listen to an interview with Ahmet Hoke, the senior author on this study: