UF Health, company develop human gene therapy trials for patients with glycogen storage disease

University of Florida Health researchers are working with a national rare-disease company to bring the first human gene therapy trials to patients with the most common form of glycogen storage disease.

Once established, the clinical trials will occur at UF Health, where much of the underlying research has occurred. UF Health is also home to the world’s largest clinical and research programs for glycogen storage disease.

Glycogen storage disease type Ia is a rare condition, occurring in about one in 100,000 people worldwide. The condition affects how sugar is stored and processed in the body after eating. Patients with this form of glycogen storage disease lack an enzyme that allows their bodies to break down and use stored sugar, resulting in low blood sugar and a buildup of glycogen in the liver.

Currently, there are no pharmacological treatments for this condition. The only treatment is for patients to receive precise doses of cornstarch at specific times throughout the day. While the treatment works, it is not ideal for long-term care, said David Weinstein, M.D., a professor of pediatrics in the UF College of Medicine and director of UF’s Glycogen Storage Disease Program.

“Although the treatment works well, it can be difficult for families to adhere to the precise schedule; for example, a missed alarm in the middle of the night could result in a child missing a dose and getting sick,” he said. “Also, even with the treatment, some patients still face complications. It is the goal of the UF GSD Program to ensure that all children and adults with this disease are healthy, and creating new treatments has been a crucial goal for our team.”

In studies of animal models with a naturally occurring, inherited form of GSD Ia similar to the disease in humans, UF researchers showed that gene therapy can correct the faulty enzyme, allowing it to naturally break down and use stored glycogen. Their findings were first reported at an American Society of Gene Therapy meeting in 2009.

Now, Dimension Therapeutics is using this research as the foundation for developing gene therapy for human clinical trials in collaboration with researchers at UF Health.

“Our research program has dedicated substantial resources to enabling gene therapy, which we ultimately hope will be the most promising approach to long-term care of patients with this condition,” Weinstein said. “New therapies are critically needed, and I look forward to working with Dimension Therapeutics to bring gene therapy into the clinic.”

In developing these therapies, Dimension Therapeutics researchers plan to focus on two adeno-associated virus vectors that specifically target liver cells. In gene therapy, a harmless virus vector is used to safely transport a replacement gene into the body. In this case, the two vectors Dimension Therapeutics is studying — AAV 8 and AAVrh10 — have been used successfully in human gene therapy for other conditions.

“Our mission — working in collaboration with patient advocacy communities and with the world’s leading clinical investigators and advisors — is to rapidly and responsibly develop new therapies that can offer hope and better health to those patients in the greatest need,” said Dimension Therapeutics CEO Annalisa Jenkins, MBBS, MRCP.