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For People With a Rare Liver Disorder, a World’s-First Gene Therapy Offers a Lifeline

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Dr. David Weinstein, professor of pediatrics at the UConn School of Medicine and director of the glycogen storage disease program.

Glycogen storage disease is a rare genetic childhood disorder that impacts the liver’s storage and release of sugar, with potentially devastating short- and long-term implications if not properly treated each day. 

For the one out of 100,000 people who are living with the various forms of GSD, a constant intake of glucose in the form of cornstarch has been the only way to stave off the threat of pain, seizures or even death, since there are currently no approved pharmacological therapies to treat GSD.

Now, however, the world’s first gene therapy clinical trial for GSD is underway at the Connecticut Children’s Medical Center and UConn Health, under the direction of pediatric endocrinologist and scientist Dr. David Weinstein. A multidisciplinary team at the Connecticut Children’s Medical Center provides comprehensive clinical care to patients, and the laboratory research is conducted at the UConn School of Medicine. 

“The trial, which just saw our sixth patient undergo this gene therapy, is going even better than expected,” says Weinstein, who has been involved in gene therapy research for more than 20 years, moving his whole team from Florida to Connecticut in 2017 when a specialized center for the GSD Program was built.

In healthy livers, excess sugar from food is stored for the body’s energy needs and is released into the bloodstream when needed as glycogen, a sugar enzyme. With GSD, the liver fails to break down glycogen into glucose, causing the body’s blood sugar levels to drop dangerously low. 

“Treating GSD with cornstarch, first prescribed in 1982, works pretty effectively, but the main problem with it is that people have to be perfect with the timing of the dosage, the accuracy of the dosage and other factors,” Weinstein says. “Oversleeping or getting busy at work and missing a scheduled cornstarch intake can lead to a rapid drop in blood sugar. When it’s infants or children relying on parents for the regular dose of cornstarch and parents sleep through the time for an overnight dose, unfortunately that can lead to serious health problems or even death.” 

The pioneering clinical trial led by Weinstein that began in Connecticut after FDA approval last year focuses on adults with GSD Type Ia. The estimated 6,000 people worldwide with GSD Type Ia can’t release glucose from the liver during periods of fasting, and the resulting hypoglycemia can be life-threatening. Also, the accumulation of glycogen in certain organs and tissues can impair their ability to function normally. Without that round-the-clock consumption of cornstarch, patients can develop severe lactic acidosis, liver tumors, kidney failure, and potentially die in infancy or childhood. The new gene therapy is administered through a single-dose injection.

“The first person in the safety trial has been able to decrease his cornstarch treatment by 91 percent, and if he misses a dose of cornstarch, he doesn’t get hypoglycemic anymore,” Weinstein says. “So this is very promising.”

Connecticut’s GSD program, the largest in the world for the care and treatment of this condition, draws patients from 49 states and 48 countries.

One of those patients, Ryan Hood, travels to Connecticut from his home in Florida every eight weeks. “I was diagnosed with GSD when I was 3 months old, have been in and out of hospitals my whole life. I’ve dealt with everything from kidney stones to unbearable nerve pain to seizures, plus the constant anxiety of missing a cornstarch dose since I was 3 years old or having my blood sugar fall to dangerous levels,” Hood says. “I’m 39 years old, and I finally have hope that I might have a healthy, happy life. I never really believed that would happen.”

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This article appeared in the June 2019 issue of Connecticut Magazine. You can subscribe here, or find the current issue on sale here. Got a question or comment? Email editor@connecticutmag.com, or contact us on Facebook @connecticutmagazine or Twitter @connecticutmag.