The same blue food dye that gives your Gatorade its turquoise tint and turns your tongue a peculiar shade of purple might also protect your nerves in the case of spinal cord injury.
By lucky accident, researchers discovered that the commonly used food additive FD&C blue dye No. 1 is remarkably similar to a lab compound that blocks a key step in nerve inflammation. When rats with spinal cord injury were given an infusion of blue dye, they recovered much faster than rats that didn’t get the treatment. And researchers reported only one adverse effect: The rats turned blue.
“One of the reasons no one had done this before is that food science is very separate from neuroscience,” said neuroscientist Maiken Nedergaard of the University of Rochester Medical Center, who co-authored the study published Monday in the Proceedings of the National Academy of Science. [http://www.pnas.org/content/106/30/12489.abstract?sid=94d0f0c1-7a4c-4039-8221-a01dc495ff13 ] “Those two fields don’t interact at all.”
Approximately 12,000 people suffer spinal cord injuries each year in the United States, mostly in car accidents or catastrophic falls. After an initial blow to the spine or neck, swelling around the spinal cord can cut off blood supply to the cord and kill additional nerve cells. A small number of patients benefit from steroids given immediately after the injury, Nedergaard said, but most continue to get worse because of secondary swelling.
“We have no treatment at all right now for most patients with spinal cord injury,” she said. “Right now we’re just observing patients get worse.”
In 2004, Nedergaard and colleagues discovered that swelling around the cord is caused by the rapid release of ATP, the molecule that normally provides energy for the cell. Excessive amounts of ATP overstimulate nerve cells and cause them to die of metabolic stress. The researchers found that blocking an ATP receptor called P2X7 prevented much of the inflammation associated with spinal cord injury. But until now, they hadn’t identified a clinically useful drug that could block the receptor.
“We just had proof of principle,” Nedergaard said. “We didn’t have anything we could give to patients.” Then, while searching for chemicals with structures similar to the P2X7 receptor, the scientists came across FD&C blue dye No. 1, completely non-toxic and approved by the FDA in 1928.
“Each of us in United States eats about 14 milligrams of blue dye per day,” Nedergaard said. “It’s in anything blue, in M&Ms, in Gatorade, in Jell-O. We eat 100 million pounds a year in the U.S., so we already know that there’s no toxicity.”
Another benefit of blue food dye is it crosses the blood-brain barrier. So instead of injecting the medicine into the spine, which would be dangerous in an injured patient, blue food dye can be delivered into a vein.
To test whether the compound could improve recovery after spinal cord injury, rats were given an intravenous infusion of Brilliant Blue G, which is nearly identical to blue food dye, 15 minutes after a 10-gram weight was dropped on their spinal cords (under anesthesia). Animals who received the blue dye recovered much faster than animals who didn’t: By six weeks, the treatment group could walk with a limp, while the no-treatment group never recovered the ability to walk.
“The paper presents novel findings, in a convincing manner,” wrote neurosurgeon Michael Fehlings of the University of Toronto, who specializes in spinal cord injury but was not involved in the research. When given 15 minutes after injury, the food dye appears to improve recovery and reduce inflammation, Fehlings said. But he pointed out several issues that need to be addressed before assuming the treatment could work in people.
“The time window of 15 minutes post-injury is not clinically relevant,” Fehlings wrote in an e-mail. Most patients don’t make it to the emergency room within 15 minutes of getting hurt, so for the treatment to work, he said, it would have to be effective at least two hours after an injury. In addition, the rats experienced injury to their middle back, while most spinal cord injuries in humans are caused by damage to the neck and upper back.
Nedergaard agrees that more research is necessary, and her group hopes to pursue a phase I clinical trial as soon they can get funding. Unfortunately, because blue food dye is so cheap, they’re not likely to find a drug company to sponsor the trials. “There’s no commercial interest because you can buy it by the pound,” Nedergaard said. “We’re planning a clinical trial here in Rochester, but we’ll have to wait for funding from the government.”