Dr. David Weinstein of the University of Connecticut School of Medicine and Connecticut Children's has presented the results from a one-year clinical trial testing a new gene therapy as a treatment for glycogen storage disease (GSD). Reporting at the Association for Glycogen Storage Disease's 41st Annual Conference, the results were called “remarkable.”
A subset of GSD, the rare genetic disorder GSD type Ia is caused by a mutation in a gene encoding for an enzyme, glucose-6-phosphatase-α, which controls the release of sugar from the liver. Blood sugar drops to dangerously low levels in affected individuals, and they constantly require cornstarch to feed their body’s need for glucose. It affects them all their lives, and missing a dose may cause a seizure or death.
The gene therapy was administered to three patients in 2018. In it, an injection to the bloodstream delivers a normal copy of the defective gene to the liver using a virus. The dysfunctional enzyme is replaced and the body can control glucose levels again.
A year after receiving an infusion of GSD vaccine, patient Jerrod Watts has been able to stop consuming cornstarch every day. His blood glucose is regulated normally, he has more strength and energy and has lost weight. Before the trial, he was ingesting over 400 grams (nearly one pound) of cornstarch on a daily basis.
"The clinical trial is going better than expected. The therapy is transforming patient lives," said Weinstein. "We have seen all of the patients wean their therapy with some already discontinuing treatment. Missed cornstarch doses no longer are resulting in hypoglycemia, which previously could have been life-threatening."
The researchers were surprised by the results of the study. "We were just making sure it was safe for humans to take, that was our initial goal. The results are way beyond my imagination," said Weinstein. "The patients who are finishing the first year got what we all thought was a test dose -- one-third strength -- yet the response has been dramatic. They can now go through the night without any treatment and they wake up clinically well."
"The main thing I want to do is inspire hope. One of the biggest reliefs from this gene therapy is I can now sleep through the night without worrying about dying in the middle of the night. I wake up six to seven hours later with normal blood sugar," Watts said. "I'm living, breathing proof that there is a light at the end of the tunnel with GSD. I'm a completely different person now that I was a year ago. I feel like I can live a normal life and I can do anything I want to do now."
He had a message for other patients: "Please don't give up hope."
The other two trial participants are also seeing good results. They have been able to reduce their cornstarch intake.
"What's exciting is if it works this well with the low dose, what does the future hold?" said Weinstein. "If the patients are already coming off cornstarch and the labs are getting better, we just hope it will be even faster and more dramatic with the higher dose."
"This gene therapy treatment is something we've worked on for 21 years. This means so much to the glycogen storage disease community," noted Weinstein. "To see patients off cornstarch and doing so well really is a culmination of an incredible journey ... We feel like we're living history."