Free to Be Imperfect

For patients and their families who live with Glycogen Storage Disease, a new gene therapy nearing clinical trial at UConn Health will mean freedom from the constant countdown to the next dose of medication.

By Julie Bartucca
Photography by Peter Morenus

Alyssa Temkin, 11, takes a break during a basketball game

Alyssa Temkin, 11, takes a break during a basketball game to drink Tolerex, the special formula that keeps her blood sugar from crashing to dangerously low levels. Alyssa has Glycogen Storage Disease and must drink the formula every 90 minutes to stay alive. Photo: Peter Morenus


Imagine never being able to hit the snooze button or oversleep, never being able to cheat on your diet or fall asleep in front of the TV because it could mean life or death — for you, or worse, your child.

That’s what the 1 in 100,000 people worldwide with Glycogen Storage Disease (GSD), a genetic liver disorder — and their parents — live with every day.

Dr. David Weinstein, who in January moved his world-renowned GSD program from the University of Florida to UConn Health and Connecticut Children’s Medical Center, has dedicated his life to giving these families hope. Although a life-saving treatment was discovered in the 1970s — taking a cornstarch mixture every few hours — research had halted for decades after that. And today, patients are still slaves to the clock; the effects of cornstarch last only a few hours, and even an extended-release form has its pitfalls.

But soon, that could change. Weinstein and his team are on the verge of testing in a human clinical trial the first GSD gene therapy, which has worked for canines and mice with the illness.

For the patients and their families who live in a constant countdown to the next feeding, the new therapy would mean freedom. A normal life, where mistakes can be made. Where they no longer have to be perfect.

There was no research going on anywhere in the world in this disease. And if there’s no research, that means there’s no hope.

Fatal Mistakes

Healthy livers store excess sugar from food and release it into our bloodstreams when we need it, as processed sugar enzymes called glycogen. However, in the seven forms of GSD, the liver fails to break down glycogen into glucose, causing the body’s blood sugar levels to drop dangerously low, which can lead to seizure or death.

The discovery of cornstarch therapy was a huge turning point, but it wasn’t enough.

“The problem with this disease is that people need cornstarch every four hours. People have died because their parents overslept,” says Weinstein. One missed alarm and a patient could die. A malfunctioning piece of medical equipment could mean a dangerous seizure.

“One of the parents was giving a talk recently and said, ‘Do you know what it’s like to have to be perfect all the time?’” Weinstein says. “And that’s what these families live with. It’s extreme stress.”

Weinstein and his team have made great strides. GSD was once considered a childhood disease — this generation is the first to survive to adulthood. Now, patients are doctors, athletes, mothers — more than 50 babies have been born to mothers with GSD since the first in 2003. But they still live under constant pressure. The disease is relentless, unforgiving.

For the patients and their families who live in a constant countdown to the next feeding, the new therapy would mean freedom. A normal life, where mistakes can be made. Where they no longer have to be perfect.

The Temkin family of West Hartford knows all too well what can happen.

When Gayle and Steve Temkin brought baby Alyssa home from the hospital at three days old, Gayle knew something was wrong with her daughter. By the time they got to a hospital that night, Alyssa was in full liver and renal failure. Her sugars were undetectable. Without intervention, she wouldn’t survive an hour, doctors said.

It was six months, several hospitals, countless invasive tests, and second and third opinions before Alyssa was diagnosed with GSD at Mount Sinai Hospital in New York City.

Alyssa is now 11, a smiling, soft-spoken sixth-grader who enjoys playing sports, acts in plays, and is learning to play guitar and dance. She gets good grades and loves her friends. But every 90 minutes, every single day, she must check her blood sugar and drink Tolerex, a special formula that keeps her sugar up. Alyssa is the only known GSD patient who can’t tolerate cornstarch, and Tolerex doesn’t last as long, so the time between her feedings is even shorter than it is for most GSD patients.

While the Temkins do everything they can to make Alyssa’s life normal, there are constant reminders that it is anything but.

Gayle spends every day at Alyssa’s school. For years, she would go into the classroom to feed Alyssa, first through a feeding tube and, more recently, with a drinkable formula. This year, Alyssa has gained some freedom. An Apple Watch reminds her when it’s time to test her blood and drink, and she reports her sugar level to her mom via a walkie talkie. Gayle, a former social worker, stays close, just in case.

If Alyssa’s sugar gets too low, she doesn’t feel it. Unlike most people, GSD patients don’t feel shaky or get headaches when their sugar drops — at least not until it’s too late. By then, they could be moments from having a seizure.

In 2015, Alyssa suffered a near-fatal seizure after the pump that feeds her dextrose through the night failed. “There is nothing about this disease that’s forgiving,” says Gayle. “It doesn’t matter what regimen you’re on; it could be a bad batch of something — We think we’re doing everything right, and the pump malfunctions.”


Dr. David Weinstein, head of the Glycogen Storage Disease Program at UConn Health and Connecticut Children’s Medical Center, walks with Alyssa Temkin through the new clinic at Connecticut Children’s.

Dr. David Weinstein, head of the Glycogen Storage Disease Program at UConn Health and Connecticut Children’s Medical Center, walks with Alyssa Temkin through the new clinic at Connecticut Children’s. Weinstein has treated Alyssa since she was diagnosed with GSD at 6 months old. Her family and other Hartford-area philanthropists supported the move of Weinstein’s program from Florida to Connecticut. Photo: Peter Morenus


No Research, No Hope

Weinstein had no intention of dedicating his life to curing GSD. As a young physician at Boston Children’s Hospital specializing in sugar disorders in 1998, Weinstein was caring for just two patients with GSD when he was invited to a national conference of the Association for Glycogen Storage Disease.

“I showed up at this meeting and was shocked by what I saw,” he says. The conference started with a moment of silence and a reading of the names of all the children who had died from GSD that year. The research presented was decades old. And the only treatment option being discussed was liver transplantation to combat complications from the disorder.

“There was no research going on anywhere in the world in this disease,” Weinstein says. “And if there’s no research, that means there’s no hope.”

A conversation with a mother there changed the course of Weinstein’s life. Knowing no one at the conference, he sat down for lunch next to Kathy Dahlberg, who had one-year-old twin sons already on the liver transplant list. She told Weinstein how sick her children were, and that her only hope was that they’d live long enough to get their liver transplants.

“Over lunch at that conference, I decided that somebody had to care about these children. The children shouldn’t have to suffer just because it was a rare disease,” Weinstein says. “The world didn’t need another diabetes doctor. This is where I could make a difference.”


Gayle Temkin talks to her daughter Alyssa in a school stairwell.

Gayle Temkin talks to her daughter Alyssa in a school stairwell. Gayle attends school with Alyssa every day, waiting in a room off the main office for Alyssa to check in via walkie talkie every 90 minutes to report her blood sugar level and that she’s drunk her Tolerex. GSD patients don’t feel the signs of low sugar until they are moments from a seizure, so Gayle stays close around the clock. Photo: Peter Morenus


As soon as he returned to Boston, Weinstein shifted his research focus to GSD and built the program there before moving it to the University of Florida in 2005 in order to work with the veterinary program. He has successfully treated dogs with his gene therapy, turning a fatal disease into one where dogs born with GSD are thriving.

Today, Weinstein sees 500 patients from 49 states and 45 countries. With help from Alyssa’s Angel Fund — started by the Temkins when Alyssa was a baby — and other charities, he has established centers all over the world.

All the Way

In January, the GSD lab moved to UConn Health’s Farmington campus. At the same time, a clinical and research unit supported financially by the Temkins and other local philanthropists opened at Connecticut Children’s. Gayle Temkin, Alan Lazowski, and Barry Stein are the trustees for the Global Center for Glycogen Storage Disease, and through the new organization will continue to raise money to support Weinstein’s program. They are working to set up other forms of assistance for patients and their families, including a closet with free supplies at the clinic, and support programs for families once the clinical trials start.

Because GSD patients are now surviving well into adulthood, the partnership between the two institutions makes great sense. “We’re much stronger working together,” Weinstein says.

Although Weinstein is the only doctor in the world dedicated to curing GSD, he says he’s not doing it alone — far from it.

“I’ve never seen a program like ours. I only do one disease. Everybody on my team does just one disease,” he says. “This is personal. Most people have a connection to the condition, and so they’ll work until everything’s done. It’s just a dedication that I’ve never experienced anyplace else.”

The bulk of Weinstein’s Florida team came to Connecticut with him. His team includes GSD patients and parents, including several who have called him out of the blue to tell him all they want is to work with him. One, who moved to Connecticut from Minnesota to join the new center, is Kathy Dahlberg, the mother who changed Weinstein’s course all those years ago. Her twins are now sophomores in college.

And, after nearly two decades of dedicated research, Weinstein’s next step is the one he’s been working toward all along. Human safety trials of his gene therapy, in conjunction with Dimension Therapeutics out of Cambridge, Mass., are expected to start this year. UConn will coordinate the trials with collaborating centers all over the world. Full-treatment trials should start in 2020.

The ultimate goal for the gene therapy, according to Weinstein,
is to prevent low blood sugars, eliminate the dependence on cornstarch, and give patients normal lives where oversleeping isn’t the worst-case scenario.

“If we can accomplish that, we’ve come all the way,” he says.

“The cure is right at our fingertips. He knew he could do this,” says Gayle. “When we first brought Alyssa to him, he said, ‘By her Bat Mitzvah, by the time she’s 12 or 13, we should be able to cure her.’ And she’s 11.

“We’re almost there.”


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