Mind Mend?

Brain trust: Don Stein is eager for progesterone to be approved for TBI treatment.

Jack Kearse

When Representative Gabrielle Giffords was shot in the head outside a Safeway during a "Congress on Your Corner" public meeting on January 8, 2011, she focused national attention on traumatic brain injury (TBI).

Until someone well-known is injured—such as Giffords, actress Natasha Richardson (who died of her injuries in a skiing accident), journalist Bob Woodruff (injured in a roadside bomb blast in Iraq)—or a pro-football player is knocked out of the game, TBI doesn't receive much attention, says Director of Emergency Neurosciences David Wright.

"No one really wants to think about it," he says. "This is an injury of young people in their twenties and thirties, who are pulled out of the workforce at the prime of their lives, and their family members become their caretakers. The loss is huge."

During the past three decades, about fifty compounds have been tested as possible treatments for TBI, and all of the studies have failed.

But a $14.5 million, national clinical trial, Progesterone for the Treatment of Traumatic Brain Injury (ProTECT III), led by Wright and based at Grady Memorial Hospital—which has become an epicenter of TBI research—is expected to change that.

The protective properties of progesterone, a naturally occurring hormone, were discovered by Asa Candler Professor of Emergency Medicine Donald Stein, director of Emory's Department of Emergency Medicine Brain Research Laboratory. As a young professor, Stein noticed that female rats fared better than male rats after brain injuries. Females, especially those who are pregnant, have higher levels of progesterone than males. "Ultimately, we learned that progesterone basically does in brain injuries what it does for fetuses—protects cells and tissue," Stein says.

Earlier, a smaller trial at Grady showed that giving progesterone to TBI patients not only was safe, but appeared to greatly reduce deaths and disability. ProTECT III, a randomized, double-blind study funded by the National Institutes of Health, seeks to confirm these findings by expanding the trial to seventeen major trauma centers across fifteen states and enrolling more than a thousand patients.

In an unusual exemption, patients in the trial can be given progesterone (or a placebo) without consent of next-of-kin—a latitude granted to researchers because success is highly dependent on the drug being administered as quickly as possible after the injury.

Stein, who has been actively studying the positive effects of the hormone on brain injury since the mid-1980s, is eager for the clinical trials to be complete and for progesterone to be given routinely to brain injury patients. "I just turned seventy-two, and I would like to see this happen," says Stein, who, even while dean of Emory's graduate school, conducted progesterone research in the evenings. "I know it works. Not a week goes by that I don't get a paper to review that confirms our findings. They come from Australia, Iran, Germany, France—dozens of labs all over the world. The data is so overwhelmingly compelling. As a scientist, I understand the need for rigorous testing and following procedure. But as a human being and a father, I find it frustrating and sometimes discouraging that it is taking so long to get this treatment out to patients."

Stein has moved on to animal studies testing progesterone's ability to reduce inflammation and brain damage in stroke victims. He is collaborating with Michael Frankel of the Marcus Stroke and Neuroscience Center at Grady (where Thomas Sowell was treated, although he did not take part in the trial), who has received an NIH grant to collect blood samples from TBI patients in the ProTECT III study. "When the brain is damaged, it releases specific proteins into the blood," Frankel says, "So the samples provide a window into the damage that has occurred."

When given systemically or by injection, Stein says, progesterone "goes everywhere in the body and affects all organs, like a broad-spectrum antibiotic. It evolved to protect the fetus. The process of repair is not really that different from development."