A Pakistani boy who could walk on burning coals propelled drugmakers on a quest for the ultimate pain treatment that can ease an ailment as old as life itself without harmful side effects. 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, AstraZeneca and Merck 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 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 defences, to compel a retreat from danger or force rest to allow healing.
While a variety of painkillers exist, none is perfect. Non-steroidal anti-inflammatory drugs, including aspirin and ibuprofen, can irritate the stomach. Merck withdrew Vioxx from the market in 2004 because of a potential link to heart attacks and strokes. Opioids, derived from poppy, are among the most- abused prescription medicines. As for the sodium 1.7channel, its a protein found in nerve cells. When a cell receives a stimulus, the tube-like channel opens and sodium ions flow into it, activating 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 had found gene mutations that heightened the sense of pain. Woodss work, funded by Pfizer, the University of Cambridge and the Wellcome Trust, was the first to establish a link between loss of the channel and an absence of distress.
Pfizer is developing compounds that block the sodium 1.7 channel. Merck aims to use the channel to treat different types of pain. The approach isnt limited to big drugmakers. Newron has developed a compound that works, in part, by targeting the channel. Its Ralfinamide is in the last stage of human testing generally needed for regulatory approval, with about 400 patients participating in Austria, Germany, India, Italy, Romania and the UK. Results are due in the first half of 2010.
All of the Pakistani children Woods studied had injuries to their lips or tongues, some requiring surgery, caused by biting themselves in the first four years of life, according to his article in Nature. Most had fractured bones, which were diagnosed later because of limping or inability to use an arm or leg. The firewalker died on his 14th birthday, before Woods could see him, after jumping off a roof.