In a world where so much has already been discovered, it is common for people to overlook the true potential of everyday chemicals. Similar to how Mustard Gas was used in World War I and then harnessed to become a potential chemotherapeutic agent, many everyday chemical substances possess great potential.
Ethoxyquin, a preservative compound in dog food seems to be one of those newly unearthed miracle workers for people suffering from chemotherapeutic side effects.
Common chemotherapeutic drugs such as Paclitaxel work by inhibiting cell division, and may be commonly used to treat solid tumors in various areas of the body. Although powerful at targeting the stabilizing of microtubules to stop cancerous cell replication, there are many negative side effects attributed to the drug such as peripheral neuropathy.
Peripheral Neuropathy is a consequence of damage to peripheral nerves that take sensory information and convey it to the brain and the rest of the central nervous system. This can be manifested as a constant tingling, numbness or burning of limbs and mouth, weakness or cramping of legs, even alongside the loss of touch sensation and body placement awareness.
Often times the effects of these toxic therapeutic agents, although life saving, can really impair an individual’s quality of life. The severity of this issue is seen in a striking 80 percent of cancer patients treated with Paclitaxel. The neuropathic effects may just be present for a couple of months after chemotherapy, but there is also a strong possibility that these intense effects become non-regressive and permanent.
Ethoxyquin, a dog food preservative and pesticide approved by the Food and Drug Administration has the potential to curtail these negative side effects. This would not only allow for a better sensory outcome for the patients receiving the therapy, but it could also allow the administration to prescribe higher doses of the drug in an effort to exterminate more of the cancerous cells.
Ahmet Hoke, the director of the Neuromuscular Division and a professor of neurology and neuroscience at the Johns Hopkins
University School of Medicine led a team investigating ethoxyquin. The Hoke lab began by surveying a wide variety of drugs with this specific target in mind, “We started with an unbiased in vitro drug screen using a 2000-compound library of potential drugs and drugs that are currently in use. We looked at compounds that prevented the toxicity of taxol [Pactitaxel market name], ddC (an old HIV drug) and capsaicin [chemical in chili peppers that causes irritation] and found EQ,” Hoke said.
A protein called heat shock protein 90 was found to be the crucial molecule in the protective effects in ethoxyquin. Heat Shock Proteins are up regulated when an organismal body is under stress in an attempt to stabilize other proteins that could be affected by that stress.
Hoke’s experiments found two proteins, ATXN2 and SP3B2 that were seemingly responsible for peripheral neuropathy through the mediation of Heat Shock Protein 90. Of the two proteins, ATXNA had been known to affect neural function, as seen with a frequent mutation that leads to spinocerebellar ataxia and amyotrophic lateral sclerosis. SP3B2 was on the other hand associated with RNA processing.
Ethoxyquin interfered with the binding of these two proteins and therefore proved to be the long searched for neuroprotective antidote to the weakening effects of chemotherapy.
Although the exact mechanism for ethoxyquin is unknown, Hoke offers some insight.
“My suspicion is that when EQ binds to hsp90, it prevents binding of SF3B2 and ataxin-2 and they are likely not folded properly and degraded,” Hoke said. This appears to be a very different technique to previously sought inhibitors that would focus on the molecules energy generating pumps.
Upon noticing the effects of drugs such as Taxol on the degeneracy of mice paw nerves, the Hoke Lab attempted to simultaneously administer Taxol and ethoxyquin. The observed nerve degeneration diminished by around 67 percent, a substantial recovery from previous trials.
Before testing the effects on mice, the Hoke Lab made sure ethoxyquin would not inhibit the efficiency of the toxic action of cancer fighting drugs. Since the drug did not impede or diminish the reduction in tumor growth in cells in the lab or in mice it was deemed conclusively promising.
The administration of ethoxyquin before or with Chemotherapeutics may indeed be what cancer patients have been in search for. And now the long process of testing and retesting begins.
Ethoxyquin’s use is not only limited to chemotherapeutic treatment, furthermore it opens doors to many other peripheral nervous system contingencies. Spinocerebellar ataxia, HIV or even diabetic patients could eventually benefit from ethoxyquin-like drugs as well.
“What I’d love to see is a drug company take the lead and do all of the preclinical studies necessary to move EQ to Phase I and II clinical trials,” Hoke said. “I’d want to focus on exploring the mechanism of its action, especially trying to understand how reducing the levels of SF3B2 and/or ataxin-2 makes neurons resistant to injury. This could be an interesting pathway to explore in terms of other neurodegenerative diseases.”
And so it goes that a therapeutic agent was found in the most unlikely of places. From a library of chemicals this synthetic antioxidant might have the potential to make more than just dog owners happy.