Duke research, Hollywood glory

Staff WriterJanuary 22, 2010 

— Only 5 years old, Clay Bowden isn't aware of the drama surrounding the drug that keeps him alive.

But he can watch the movie, which is released today.

"Extraordinary Measures," starring Harrison Ford and Brendan Fraser, tells a fictionalized account of how a real drug came to market in 2006 and saved hundreds of youngsters, including Bowden, afflicted with the rare metabolic disorder Pompe disease.

And though movie trailers boast that the film is inspired by a true story - Fraser's character, John Crowley, is real - the drug development occurred at Duke University by scientists who look and behave nothing like the crotchety loner Ford plays.

"I'm incredibly proud of what we've done," said Dr. Priya Kishnani, a pediatric geneticist who helped lead clinical trials at Duke that resulted in the drug's regulatory approval.

She is frustrated that Duke was written out of the movie, but Kishnani said she's pleased that attention is being drawn to Pompe disease, which had been a childhood death sentence before the drug was available.

In the movie, credit for the drug's development goes to Ford's character, Dr. Robert Stonehill, a make-believe angry scientist whose genius is unappreciated until Crowley arrives.

The movie character and real-life Crowley is a Harvard-educated bio-tech executive and father of two children diagnosed with Pompe. After his children grew sick, Crowley quit his job and raised venture capital money to sponsor what he thought was a promising drug candidate.

In fact, the drug Crowley backed never made it out of the laboratory. Instead, Genzyme, the pharmaceutical company that bought Crowley's start-up, pressed ahead with a more effective therapy based on Duke's science.

That treatment replaces an enzyme that people with Pompe disease do not produce at all, or at severely low levels.

The enzyme prevents the buildup of the starch glycogen, much as insulin prevents the buildup of glucose. As glycogen accumulates, it degenerates muscles.

Babies born with Pompe were destined to die within their first year. It was also eventually fatal to older children and adults whose disease surfaced later.

Effort takes flight

Duke researchers began pursuing treatments for Pompe disease in the 1990s, led by Dr. Yuan-Tsong Chen, a pediatric geneticist who used DNA technology in the ovary cells of Chinese hamsters to produce the missing enzyme.

The Duke team first tested the drug in quail that were so impaired they couldn't stand or even roll over. The enzyme worked, and one of the birds flew.

In 1999, Duke began clinical trials in humans. Three children were enrolled; one responded well, and the other two eventually died. Given the lethal nature of Pompe, those odds of survival were a huge improvement.

Overwhelmed with interest from desperate parents - including Crowley, who breached ethical considerations with unsuccessful attempts to get his children enrolled in the early tests - Duke led a second trial. Again, it showed promise.

"With the experience we gained from the earlier trials, we learned several lessons," Kishnani said. "The earlier we started, the better the results."

The third and largest clinical trial had the strongest results, and the Food and Drug Administration granted approval for the drug, Myozyme, in 2006.

Kishnani said it was a heated time. Parents throughout the world called Duke or simply showed up in Durham seeking the enzyme infusions to save their children. But the drug was difficult to make and in short supply, so it was reserved for clinical trial participants and a few babies who would otherwise have died.

Clay Bowden, of Cumberland County, was among the lucky few. Born before the drug was approved, but too late to participate in the clinical trial, Clay received Myozyme at the age of 3 months under a so-called compassionate use waiver from the FDA .

The road to help

Now, five years later, he makes a two-hour trip with his grandmother, Rebecca, from Linden to Duke every week for infusions. While Clay plays video games and watches movies, an intravenous line drips Myozyme into his body through a port on his stomach. It's a regimen he'll keep for the rest of his life.

A spirited kindergartner, he has a speech impairment and wears braces on both feet. But he plans to playT-ball again this spring.

"It's a miracle for him," Rebecca Bowden said.

Kishnani said work on the drug continues, as researchers try to find ways to boost its effect and get it to babies sooner. The Duke team is also working to get Pompe disease added to the battery of metabolic disorders screened for at birth.

The movie, she said, could help in that effort.

"It brings about great exposure," she said, even if the picture doesn't tell the full story.

savery@newsobserver.com or 919-829-4882

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