When the film Extraordinary Measures debuts on January 22, it will tell the story of one man's quest to obtain treatment for his children who suffer from a rare metabolic disorder called Pompe disease.
The real story began 20 years ago at Duke University Medical Center when pediatric geneticist Y.T. Chen, MD, PhD, began work on the first and only life-saving treatment for Pompe.
In 2006, the FDA approved the use of Myozyme, which is manufactured and marketed by Genzyme Corporation, based on Duke's research. As a result, the children portrayed in the movie, and those who are living with Pompe worldwide, were treated with Myozyme and given their first fighting chance at life.
What Is Pompe Disease?
Pompe disease results when mutations occur in the gene that triggers the production of an enzyme called acid alpha-glucosidase (GAA). That enzyme is responsible for helping the body break down glycogen (sugar).
When it is absent or deficient the glycogen builds up in the body's cells, damages tissues and causes progressive heart and skeletal muscle weakness.
About one in 40,000 people have Pompe disease. In adults, the disease progresses slowly, and can result in reduced motor abilities and difficulty breathing.
It progresses more rapidly in the 30 to 35 infants born with Pompe in the U.S. annually, who would die in the first year of life without treatment. In infancy, the disease causes the heart muscle to enlarge and thicken, babies are weak and have difficulty breathing, explains Priya Kishnani, MD, a pediatric geneticist at Duke who is the world's leading expert on Pompe.
"Myozyme is to Pompe disease what insulin is to diabetes," Kishnani explains.
"It does the job of the missing or malfunctioning enzyme. Given via four-hour intravenous infusions every two weeks for the rest of a patient's life, Myozyme successfully improves heart and muscular function. With its use, children are able to meet their motor milestones, they are running, going to school and playing games."
Journey from Bench to Bedside
Myozyme's journey started in 1995 when Chen engineered a line of cells that could produce the GAA enzyme. Within one year, animal studies proved fruitful when birds missing the enzyme went from being unable to fly to flipping from their backs to their feet after several days of infusions. One of the birds even flew.
Kishnani was the lead investigator of the trials that would take Chen's work out of the lab and into humans. Clinical trials started in 1999 with three frail babies.
Today, one of those babies is a healthy, 11-year-old boy who plays baseball and enjoys a normal life. "You couldn't pick him out from a crowd," Kishnani says. But with only 11 years of experience, she cautions that it's too early to predict the future.
"There are patients who have done remarkably well but others have not. We've learned that early initiation of treatment is paramount to a successful outcome."
It's the reason why Duke and others are pushing to include Pompe and other rare genetic diseases in the battery of newborn screening.
In Taiwan, where newborn screening includes Pompe, published studies reported a far superior outcome in babies who were identified with Pompe at birth."They are walking and have made marvelous motor gains," Kishnani says. The motor gains of children who were identified later "are not as robust."
What the Future Holds
Kishnani and her team continue to do research aimed at enhancing the longevity and quality of life for patients with Pompe.
One avenue is exploring strategies that will avoid the immune response that sometimes occurs when the body recognizes Myozyme as foreign. Another approach focuses on better muscle delivery of the enzyme therapy. The role of gene replacement therapy is also being explored as well as the significance of diet and exercise.
Duke researchers worked with others to develop a blood test to take the place of an invasive skin or muscle biopsy. "This simple drop of blood lets us diagnose patients in as quickly as 24 hours," Kishnani says.
As the world is about to learn of a disease that has consumed her life, Kishnani sits back and smiles. "I never would have expected that a major Hollywood movie with stars like Brendan Fraser and Harrison Ford would focus on a topic so near and dear to my heart. The movie is a win-win for all of us in the field, but especially for the patients because the more awareness there is, the more likely they will be diagnosed early and treated."