Treatment for Adult-onset Pompe Disease Tried in First U.S. Patient

Tom Valeo
September 10, 2010
Monique_Griffin feature
Monique Griffin

In January, 10 years after she first noticed symptoms, Monique Griffin finally received the correct diagnosis: Pompe disease.

Until recently, this news would have been devastating, since it would have meant a life of progressive weakness and disability. But Griffin has become the first adult in the United States to receive an effective new treatment for the rare disorder. Griffin never worried much about her growing weakness. In college, she studied in England and Wales, and when she got a job with Wynn Resorts, she spent a year in China helping to open the Wynn Macau. She figured everyone got weaker by the time they were in their mid-20s.

“I just thought, I’m not a teenager anymore,” said Griffin, 35, of Orlando. “I’m not in dance anymore; I’m out of shape. I didn’t even notice the muscle weakness until a doctor pointed it out.”

What the doctor noticed was how she placed her hands on the armrests of a chair and used her arms to lift herself to a standing position. “He said, ‘cross your arms over your chest and try getting out of the chair again,’” she recalled. “I couldn’t do it.”

The original diagnosis was inflammatory myopathy—an inflammation of the muscle cells—and the treatment involved taking steroids, which have many potential side effects, including weight gain.

“All I saw were the side effects,” Griffin said. “I wasn’t getting any stronger, so I asked to be taken off the steroids. I decided to live with the weakness.”

But last year Griffin visited a neurologist who doubted the inflammatory myopathy diagnosis. He sent her to the Mayo Clinic, where a muscle biopsy and a blood test determined that she had adult-onset Pompe (pronounced pom-PAY) disease, a genetic disorder that prevents the body from making sufficient amounts of the enzyme needed to break down glycogen into glucose, which muscles use for energy. As a result, glycogen accumulates and chokes muscle cells, causing progressive weakness.

Adults with Pompe can expect to grow progressively weaker until they need a wheelchair all the time. They become increasingly incapacitated, and often die prematurely.

Griffin, however, was among nearly 200 adults in this country who received periodic infusions of Lumizymea drug developed by Genzyme for people with adult-onset Pompe disease. They were participants in a program known as the Alglucosidase Alfa Temporary Access Program (ATAP), and when the drug received FDA approval in June, she became the first person to receive a commercial infusion.

The drug delivers the enzyme that cells need to break down glycogen, and Griffin’s progressive weakness appears to have halted. She’s even started to feel stronger.

“I really think it’s working,” said Griffin, who received her first treatment on June 16. “I’ve had 8 infusions—one every other week—and after 4 or 5 infusions I noticed improvements in my stability. I could walk short distances without getting as tired, and I was more stable on my feet. In the last two weeks I’ve noticed that getting out of a chair, while still a struggle, is not as hard.”

She hopes that soon she will be able to get around without relying so much on her motorized scooter. “I’d like to be able to walk further,” she said. “I’d like to be more independent, but Pompe affects everyone differently, and the treatment is so new that there are no long-term studies.” (Griffin maintains a blog at

Genetic source

Pompe disease is a form of muscular dystrophy caused by a mutation in the gene on chromosome 17 that codes for acid alpha-glucosidase, or GAA, an enzyme essential for breaking down glycogen. About one baby in 138,000 is born with the infantile form of the disease, and about 1 in 57,000 is destined to develop adult-onset Pompe. About 5,000-10,000 people in the United States are believed to have the disease.

Babies born with a mutation that results in no GAA production at all grow progressively weaker as glycogen builds up and clogs muscle cells, including those in the heart. They start to develop progressive weakness shortly after birth, and usually die in childhood of heart failure, often before age 2.

Children who develop juvenile onset Pompe disease are born with a gene that produces some GAA, but not enough. As a result they develop milder but still progressive weakness.

People like Griffin, with adult-onset Pompe disease, possess a mutation that allows them to produce even larger amounts of GAA, but not enough to clear glycogen completely from their muscle cells. As a result, the accumulation is slower and symptoms do not appear until the third decade of life or later.

The quest for a treatment for Pompe was chronicled in The Cure, a 2006 book by Geeta Anand that was made into the film “Extraordinary Measures.” In the film, Harrison Ford plays a doctor intent on finding a way to supply the enzyme that Pompe patients lack. Supplying the enzyme itself does no good, his character explains, because it doesn’t get into the lysosome, where cell products are broken down. However, when the enzyme is designed to attach to a specific receptor, it is readily absorbed by the lysosome, allowing the breakdown and clearance of glycogen.

The book and film were inspired by the story of John Crowley and his wife, parents of two children with Pompe disease. They collaborated with William Canfield, a glycobiologist, to form Novazyme, devoted to producing the replacement enzyme. In 2001 Novazyme was acquired by Genzyme, which eventually developed Myozyme, a slightly different replacement enzyme developed by Yuan-Tsong Chen, then at Duke University, and Ans T. van der Ploeg and Arnold J.J. Reuser in the Netherlands.

Myozyme, a treatment for infants with Pompe disease, was approved by the FDA in 2006. Lumizyme, for adult-onset Pompe, while essentially identical biologically, must be made in larger batches, and required separate FDA approval, which was granted in May 2010.

Myozyme and Lumizyme are extraordinarily expensive—approximately $200,000 to $300,000 or even more for each year of a patient’s life—and administration of the drug is time-consuming.  Every two weeks, Griffin must drive from her home in Orlando to the University of Florida in Gainesville, two hours away, and spend four hours receiving an infusion of Lumizyme. “It’s a whole-day ordeal, “ she said.

Still, Genzyme is committed to making the drug available to all who need it, including all who received it through ATAP. “No patient is ever denied access to therapy because of an inability to pay,” said Genzyme spokesperson Lori Gorski. “Through ATAP, Genzyme has provided therapy to nearly 200 patients free of charge.”

The treatment appears to work, although it may not reverse some of the long-standing problems adult patients develop, said Barry Byrne, a pediatric cardiologist and the director of the Powell Gene Therapy Center and a member of the University of Florida Genetics Institute.

“It appears that as patients get older, there are secondary changes to muscles either from longstanding weakness or from disuse, or maybe both,” said Byrne, who treats Griffin and other Pompe patients.

Such changes probably could be prevented if treatment began earlier. For example, newborn screening could identify babies who carry the mutation that causes Pompe disease, and diagnostic techniques could find the disease in adults long before symptoms begin.

But the expense of the treatment provides an incentive to wait until symptoms appear.

“The cost and inconvenience of treatment are enormous,” Byrne said. “Think of 50 or 60 or 70 years of bimonthly infusions. If you have lifetime insurance cap of $2 million, you’re likely to think, ‘as long as I can walk I’m not going to start using that up.’ This is common in genetic diseases—the pathology is present before birth, but the conventional wisdom is to begin treatment only when the patient develops deficits, and studies show that may be too late.”

Byrne is working on another approach to Pompe disease—direct manipulation of the defective gene. He and his colleagues have already succeeded in delivering a correct gene to the diaphragm of a mouse with a version of the disease, and a clinical trial involving six infants with Pompe disease began this summer.

“I think there are opportunities for additional approaches as well,” he said.