Extracts

Gene Therapy Offers Hope For Sugar Disorder

April Frawley Birdwell

A dog born with a deadly disease that prevents the body from using stored sugar has survived for two years 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, these dogs all die,” said Dr. David Weinstein, director of the UF Glycogen Storage Disease Program and co-investigator on the study. “People usually survive because they are fed so much as infants. But by 4 to 6 months of age, they will have developmental delays and a big liver. If it is diagnosed at that point, the kids can do fine. 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.”

UF researcher Cathryn Mah, a member of the Powell Gene Therapy Center and UF Genetics Institute, presented the findings at an American Society of Gene Therapy meeting.

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, which 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 AAV. Six weeks after the therapy, the dog was completely weaned off glucose supplements.

“We have never had to use any glucose supplementation since we weaned her off,” Mah said. “She just gets fed normal dog food. That is a huge improvement in quality of life.”

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.

Researchers hope to eventually establish a clinical trial in humans, but for now would like to test gene therapy in dogs again within the next year, Weinstein said.

The study was funded by the Children’s Fund for Glycogen Storage Disease Research.

Cathryn Mah, cmah@ufl.edu