The medication initially known as VX-548 blocks sodium channels in nerves, blocking pain signals before they reach the brain
hen doctors ask Sara Gehrig to describe her pain, she often says it is indescribable. Stabbing, burning, aching—those words frequently fail to depict sensations that have persisted for so long they are now a part of her, like her bones and skin. “My pain is like an extra limb that comes along with me every day.”
That drug, a pill called VX-548, blocks pain signals before they can reach the brain. It gums up sodium channels in peripheral nerve cells, and obstructed channels make it hard for those cells to transmit pain sensations. Because the drug acts only on the peripheral nerves, it does not carry the potential for addiction associated with opioids—oxycodone and similar drugs exert their effects on the brain and spinal cord and thus can trigger the brain’s reward centers and an addiction cycle.
A young Pakistani firewalker had a genetic mutation affecting pain-signaling neurons, letting the boy walk on burning coals without feeling pain.he pain medications that exist today are, in large part, derivatives of natural products that have been around for thousands of years. Aspirinwillow bark. Morphine and codeine were derived from the opium poppy plant.
“It’s a very quick process, faster than the human eye can detect, but incredibly rich in information,” says Paul Negulescu, Vertex’s senior vice president of research and head of its pain program. The engineering group developed the first generation of the technology about, and it is on the third generation now. “That’s been the workhorse. And we have tested tens of thousands of compounds on the system that runs every day,” he adds.
The drug provided less relief than Vicodin for bunionectomy patients when using a different pain scale. Still, those taking VX-548 reported fewer side effects—such as nausea, constipation, headache and dizziness—than those on the placebo, indicating the treatment was generally safe. Waxman says the Vertex findings were modest yet important—so important that he called VX-548 “a game changer,” not because it will change clinical practice on its own but because it will transform the research pipeline. “This is going to be like the development of the statin drugs,” he says. “The first statin drugs were, in retrospect, not very good. But they set the stage and really were the impetus, and the ones we have now are life-changing.
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