UF gene therapy in dog promising for humans

Treatment is for glycogen storage disease type 1A


Dr. David Weinstein checks in on a patient with glycogen storage disease.

COURTESY OF UF
Published: Monday, June 1, 2009 at 12:50 p.m.
Last Modified: Monday, June 1, 2009 at 12:50 p.m.

A dog born with a deadly disease that prevents the body from using stored sugar has survived 20 months and is still healthy after receiving gene therapy at the University of Florida — putting scientists a step closer to finding a cure for the disorder in children.

Called glycogen storage disease type 1A, the genetic disease stops the body from being able to correctly store and use sugar between meals. In order to survive, children and adults with this disease must receive precise doses of cornstarch every few hours.

The disease is even more dire in dogs, which must be fed sugar every 30 minutes to survive. Without treatment, the dogs die.

Human infants, however, usually survive because they are fed to much and so often, according to Dr. David Weinstein, director of the UF Glycogen Storage Disease Program and co-investigator on the study.

“But by 4 to 6 months of age,” Weinstein said, “these babies will have developmental delays and a big liver.”

If they are diagnosed with glycogen storage disease at that point, the kids can do fine. Weinstein explained.

“But if it is not diagnosed, then the kids get exposed to recurrent low sugars, and they will end up with brain damage, seizures or they will die,” he said.

With more than 300 patients from 18 countries, UF’s glycogen storage disease program is the largest in the world.

Cathryn Mah, a researcher in the Powell Gene Therapy Center and UF Genetics Institute, is presenting the study findings at an American Society of Gene Therapy meeting this weekend in San Diego.

About one in 100,000 children have this severe form of glycogen storage disease. Children receive doses of cornstarch at scheduled intervals throughout the day because it metabolizes more slowly than other carbohydrates. Until this therapy was discovered about 30 years ago, most children born with this disease did not survive past infancy.

Glycogen storage disease type 1A stems from a faulty enzyme that doesn’t convert stored sugar, or glycogen, to glucose, the type of sugar the body uses for energy. This prevents the body from getting the energy it needs and causes glycogen to build up in the liver.

The goal of gene therapy is to restore the faulty enzyme so the body uses sugar properly, said Mah, a UF assistant professor of pediatric cellular and molecular therapy and a co-investigator on the study.

The dog, named Dulce, is a beagle-Maltese mix. She comes from a line of dogs genetically prone to the disease, received its first dose of gene therapy the day after it was born, Mah said. The dog improved at first, often going as long as two to three hours without needing additional glucose to supplement its diet. But several weeks later the progress stopped.

When the dog was 5 months old, the researchers administered another dose of gene therapy, this time using a different type of adeno-associated virus to deliver it. Six weeks after the therapy, the dog was completely weaned off glucose supplements.

The 20-month-old animal now is living a typical dog’s life, eating normal dog food and doing without any extra glucose.

A few years ago, when Weinstein, Mah and other UF and National Institutes of Health collaborators began discussing the project, the longest a dog with the disease had lived was 28 days.

“The success is beyond what I would have imagined at this stage,” Weinstein said. “To have a dog off treatment for 14 months that is clinically doing great with outstanding lab results is beyond anything I even dreamed about.”

Before trying the gene therapy approach in humans, researchers will test it again in dogs within the next year, according to Weinstein.

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