A UConn Health Team Administers the World’s First Gene Therapy for Glycogen Storage Disease Type-1a

In January of this year, a University of Connecticut (UConn) team administered the world’s first infusion of a new gene therapy as part of a long-awaited clinical trial.

According to an article in UCONN Today, the Phase 3 clinical trial has the potential to change the lives of many other patients with GSD.

Glycogen storage disease (GSD) type 1 (GSD1) is a disorder whereby stored glycogen is not metabolized into glucose. Therefore, the body is not supplied with sufficient energy, and blood glucose levels are unstable.

GSD1 is inherited and characterized by an accumulation of fat and glycogen in the kidneys and liver. The result is enlarged kidneys and liver, and eventually retarded growth. The disease can be fatal.

The Way It Was

GSD was a fatal disease until the discovery of continuous glucose therapy to prevent hypoglycemia. Then, in 1982, cornstarch therapy was found to slow the release of glucose.

However, GSD patients had to drink water and cornstarch daily every three or four hours. A fifteen-minute delay in schedule could result in seizures or even death.

The Phase 1/2 trial testing the procedure resulted in a seventy percent decrease in participants’ needs. Some participants who had been dependent on a four-hour schedule of cornstarch were able to extend the time to twelve or fifteen hours.

Patience and Dedication

David Weinstein, M.D., and a team at UConn Health administered the first gene therapy to a GSD-1a patient in 2018. At the time Dr. Weinstein was director of the GSD Program at UConn Health. For the past 20 years, Dr. Weinstein had been working toward a breakthrough.

Dr. Weinstein recently left UConn Health to begin research on other rare diseases. He was replaced by Rebecca Wolman, M.D., as the director of UConn’s GSD division.

The Phase 3 Trial

The trial is a blinded control study whereby fifty percent of enrolled patients are to receive the actual product while the other fifty percent will be given a placebo. None of the participants or investigators will receive any information that would identify the recipients of either the product or the placebo.

The parents of the first trial participant were on-site during the 45 minute infusion while the family attended via FaceTime.

The gene therapy moves through the patient’s bloodstream transported by a harmless virus. When it reaches the liver, it replaces the deficient sugar enzymes that cause the disease. This will jump start glucose control.

The patient is then monitored for three days as an inpatient in the clinical trial inpatient unit.

Participants in the study will report data such as food and cornstarch intake on a daily basis. Blood sugar numbers, checked by a Descom glucose monitor, will be sent directly to study coordinators.

The study subjects will return to UConn Health every three months to participate in a fasting study. The Phase 3 trial will be completed in two years, however, after one year those receiving a placebo may switch to the product being investigated.

When the trial is completed, the results will be published. The goal is to make the treatment available for all GSD-1a patients.

About the First Trial Participant

The patient’s name will not be disclosed in order to preserve the double-blind trial’s integrity. The patient, who was first diagnosed at five months, was brought to Dr. Weinstein three months later. The baby’s father recalled that glucose was fed to the baby through a feeding tube.

Now a young adult, the patient is given Glycoside, a ‘superstarch’ which was FDA approved in 2012. Glycoside maintains blood sugar levels for up to eight hours.

The patient also uses the Dexcom glucose monitor that not only connects to the patient’s cell phone but also to a friend or family member’s cell phone to be on alert for abnormal levels. This feature is being used by trial investigators.

A Tribute to Dr. Weinstein

Juan Salazar, M.D., Chief Physician of pediatrics at UConn’s pediatrics department, gives credit to Dr. Weinstein and the collaboration of UConn Health and the Pediatrics Department for conducting the world’s first Phase 3 trial for GSD. Dr. Salazar notes that it is especially remarkable to be conducting the trial during the COVID epidemic while UConn Health has had the largest number of COVID cases ever.

The team has been working in conjunction with Ultragenyx Pharmaceuticals of Novato, California, a biopharmaceutical company. Their primary goal is to test the dosage and safety of the gene therapy for GSD-1a patients. The GSD community was generous with donations and support.

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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