The Glycogen Storage Disease Program at Connecticut Children’s and UConn Health reported success in a Phase I/II trial of a gene therapy for GSD-Ia.
A potential treatment for Glycogen Storage Disease is on its way. (Spencer Platt/Getty Images)
The Glycogen Storage Disease Program at Connecticut Children’s and UConn Health reported success in a Phase I/II trial of a gene therapy for GSD-Ia.
Glycogen Storage Disease Type Ia (GSD-Ia) is a metabolic disease in which the liver is unable to break down glycogen into glucose. This causes blood sugar levels to plummet. It can damage the kidneys and liver, with serious side effects, including death. In order to prevent seizures and death, patients drink a cornstarch and water solution every couple of hours, but they can’t miss a dose by even 15 minutes.
Dr. Rebecca Riba-Wolman, director of the Glycogen Storage Disease Program, and a member of the Division of Pediatric Endocrinology at Connecticut Children’s said, “The participants of the Phase I/II trial overall have seen a 70% decrease in cornstarch needs. Some participants who could previously not go more than four hours without cornstarch are now able to last from 12-15 hours, significantly changing their lives.”
What is the Cause of Glycogen Storage Disease?
Glycogen Storage Disease Type Ia is caused by a defective gene for the enzyme glycose-6-phosphatase (G6Pase). The gene therapy is developed with Ultragenyx and is dubbed DTX401. It is an investigational AAV8 gene therapy engineered to deliver stable expression and activity of G6Pase-alpha using a single intravenous infusion.
The UConn and Connecticut Children’s program was initiated by Dr. David Weinstein, who left to become Vice President, Clinical Development for PassageBio, which focuses on central nervous system disease.
“Dr. Weinstein left me with an incredible team of people and I couldn’t do this without them,” Dr. Riba-Wolman said. “Including co-principal investigator Dr. Karen Loechner, and nurses with GSD and ICU experience, the team also includes a metabolic dietician, Malaya Mount, who monitors the participant’s diet and cornstarch intake based on the data from their glucose monitor.”
On January 18, 2022, the inpatient clinical trial unit at UConn John Dempsey Hospital infused the first Glycogen Storage Disease patient in the Phase III trial of the gene therapy. In the study, 50% of participants will receive the therapy, and 50% will receive a placebo. It is blinded and is planned to last two years. After the first year, depending on the success of the therapy, anyone who received the placebo will be shifted to gene therapy.
The first participant in the trial was first diagnosed at the age of five months. The patient is now a young adult and, instead of a water-corn starch solution, takes Glycosade, which was approved by the U.S. Food and Drug Administration (FDA) in 2012. It is a “superstarch” that maintains blood sugar levels for seven to eight hours overnight.
Dr. Juan C. Salazar, Physician-in-Chief, Connecticut Children’s and Department Chair of Pediatrics at UConn School of Medicine, said, “This is very exciting. It’s a culmination of over 20 years of research initiated by our colleague Dr. David Weinstein, who was the visionary and who had the lasting capacity to move this from an idea to the animal model to trial that we are now in, Phase III, and closer to bringing this innovative, life-changing gene therapy to the broader Glycogen Storage Disease community. To me, this is very exciting that together, UConn Health, the Department of Pediatrics at the UConn School of Medicine, in partnership with Connecticut Children’s, are able to be the first in the world to move to the next phase of the trial.”
