DURHAM, N.C. -- The U.S. Food and Drug Administration has approved Duke University's application for Orphan Drug Designation for a new therapy for Pompe disease, an inherited and usually lethal glycogen storage disease that often afflicts children, Duke officials announced.
This designation makes Duke eligible for FDA grants to support a clinical trial of the therapy. Duke University Medical Center researchers hope to begin that trial in 1998.
Pompe disease is an incapacitating condition caused by an inherited deficiency of the enzyme acid alpha glucosidase. Acid alpha glucosidase normally degrades cellular stores of glycogen into glucose, a primary energy source. Patients suffering from Pompe disease lack sufficient enzyme for that chemical conversion. As a result, glycogen accumulates and destroys skeletal, heart, and lung muscles.
Pompe disease is rare, affecting approximately one child out of every 100,000. If symptoms appear during infancy, death usually occurs before the age of 2. The disease is usually less severe when symptoms first appear later in childhood, but life expectancy extends only into the second or third decade in such cases. Adults can be affected by a milder form of the disease but are still incapacitated due to respiratory insufficiency.
Initially, the therapy developed at Duke will be tested in infants with the most severe symptoms and for whom the disease is fatal. The Duke clinical trial will test a genetically engineered form of the enzyme, expressed in a cell line developed in the laboratory of Dr. Y.T. Chen, chief of the Division of Medical Genetics in the department of pediatrics.
Initially, the drug will be tested in a small number of Pompe disease infants to evaluate the safety and efficacy of the recombinant enzyme treatment. Enrollment will be based on strict FDA-approved clinical criteria.
Chen, who will lead the clinical trial, anticipates that recombinant enzyme injected into infants will be taken up by their muscle cells and restore normal glycogen levels. This treatment, known as an enzyme replacement therapy, would be required for the rest of these patients' lives.
He said he hopes to expand the treatment to additional Pompe disease patients as safety and efficacy are demonstrated and supplies of the enzyme are available.
Chen's team at Duke has spent more than five years developing the cell line that produces the recombinant drug. The work was funded by a combination of private contributions, foundation grants, and industrial support from Synpac Pharmaceuticals Ltd. in the United Kingdom.
If the enzyme replacement therapy proves successful and gains FDA approval, Synpac will continue to manufacture and market the drug.
Commenting on the FDA action, Chen said, "After treating patients who have very little hope and working on this therapy for so many years, I look forward to working with the FDA to bring this therapy into the clinic. This is a major milestone in our efforts to develop an effective treatment of this fatal disease."
Dr. Michael Frank, chairman of the department of pediatrics at Duke, added: "Dr. Chen's efforts are an excellent example of the way that basic research and clinical applications come together at Duke to provide care for children and hope for their families. He is building this new therapy while we are building our new Children's Hospital.
"I hope that his efforts and ours converge in the near future and that we will be able to provide enzyme replacement for Pompe disease as one of the advanced therapies we offer in our new outpatient children's facility in the near future."