Firewalkers Faulty Gene May Shake Up Market For Painkillers
Geoffrey Woods, a geneticist at the University of Cambridge, was studying families that had intermarried in northern Pakistan when he heard about the boy, who felt no pangs as he performed stunts on the street. Research on other children in the area uncovered a faulty gene among them. They all were healthy and had a normal sense of touch.
Woodss findings, published in the journal Nature, spurred Pfizer Inc., AstraZeneca Plc and Merck & Co. to study drugs that work like the gene mutations by interrupting a channel that transmits pain signals. While that research is at an early stage, Newron Pharmaceuticals SpA of Italy has a product in human tests. Those studies may lead to treatments that have fewer side effects than many painkillers, which London-based Datamonitor Plc says generated $24.3 billion in sales in 2007.
“Its the ultimate target,” said John Wood, a professor of molecular neurobiology at University College London who co- wrote the Nature article with Woods in December 2006. “The people that dont have the channel are not ill, they have no problems, so if you find a drug that blocks it, they should be pain-free and also free of side effects.”
Pain is one of the bodys natural defenses, intended to compel a retreat from danger or force rest to allow healing.
Drawbacks
While a variety of painkillers exist, none is perfect. Non- steroidal anti-inflammatory drugs, a group that includes aspirin and ibuprofen, can irritate the stomach. Merck withdrew its Vioxx medicine from the market in 2004 because of a potential link to heart attacks and strokes. Opioids, which are derived from the opium poppy and include morphine, are among the most- abused prescription medicines.
The sodium 1.7, or Nav1.7, channel is a protein found in nerve cells. When a cell receives a stimulus, the tube-like channel opens and sodium ions flow into it, activating the nerves. They send an electrical signal to the spinal cord and the brain, which interprets it as pain.
In people with the gene mutations found in the Pakistani children, the sodium channel is incomplete, interrupting the chemical cascade that leads to pain sensation.
Early research on the channel, first identified in the mid- 1990s, had found gene mutations that heightened the sense of pain. Woodss work, funded by Pfizer, the University of Cambridge and the London-based Wellcome Trust, was the first to establish a link between loss of the channel and an absence of distress.
Peripheral Neurons
“Geoffs paper demonstrated that you can basically live without having Nav1.7, and for a drug company that is the most important finding they can have in defining a drug target,” said Sulayman Dib-Hajj, a neurology researcher at the Yale School of Medicine in New Haven, Connecticut, who was involved in early studies of the channel.
“The mere fact that the Nav1.7 sodium channel is primarily expressed in peripheral neurons means youre not going to worry about an effect on the heart or on the brain or on the spinal cord,” Dib-Hajj said. “And thats why it has become a very important target in the quest for new painkillers.”
Pfizer, based in New York, is developing compounds that block the sodium 1.7 channel, though they have yet to be tested in people. The channel is “high profile for us and we believe were making great progress,” said Gillian Burgess, head of the pain group at Pfizer.
Early Development
AstraZeneca, based in London, is also in early development of such compounds, said Neil McCrae, a company spokesman.
Merck of Whitehouse Station, New Jersey, aims to use the channel to treat different types of pain, said Stefanie Kane, senior director in Mercks pain research unit.
“We have initially identified compounds that in preclinical analysis are at least 100 times more potent than currently available drugs as inhibitors of this target,” Kane said in an e-mailed response to questions. She declined to say how advanced development is.
From 80 percent to 90 percent of experimental drugs fail to get through preclinical tests, the phase that occurs before human trials, according to the U.S. National Institutes of Health, in Bethesda, Maryland. It takes an average of eight years to get a drug through human testing and regulatory review, according to the Tufts Center for the Study of Drug Development, in Boston.