UConn Health Glycogen Storage Disease Lab
Dr. Lee’s laboratory at UCONN was created exclusively for GSD research, where scientists work
toward developing cures through preclinical research using animal models of GSDs.
The lab raises awareness about GSD and gene therapy among research communities, collaborating
with research groups around the world. The lab is central to the clinical GSD program team at UConn
Health/Connecticut Children’s Medical Center, and participates in monthly "Bench to Bedside"
meetings to discuss findings from both basic sciences and clinical cares.
Ongoing Research Project on GSD-Ia
Evaluation of AAV-neutralizing antibody digesting enzyme in murine model of Glycogen Storage
Disease Type Ia:
To date in the Phase 3 clinical trial of AAV8-mediated GSD-Ia gene therapy, the cohorts that received
the gene therapy have shown sustained efficacy. While this is positive, it is also clear that it is not a
permanent cure. Going forward, all patients will require redosing. However, as normal response to
any kinds of virus, human body produces “neutralizing antibody” against the AAV8 gene therapy, and
it disables the gene therapy. Therefore, the cohorts who received the first dose should have the
neutralizing antibodies to the AAV gene therapy, so the second dose will not work for the cohorts
Additionally, a large number of GSD-Ia patients carry pre-existing neutralizing antibodies against
AAV8; these individuals have already been excluded from the current clinical trial.
Thanks to The Children's Fund for Glycogen Storage Disease Research, the lab has initiated a project
to evaluate neutralizing antibody-digesting enzymes in GSD-Ia gene therapy. The redosing efficacy of
AAV8-hG6PC will be evaluated in a GSD-Ia mouse model. Once an optimized condition is identified
in the preclinical model, the lab will offer recommendations for the clinical translation of the GSD-Ia
Future Project Under Development:
AAV-mediated treatment allows for the delivery of a functional copy of G6Pase-α to liver cells.
However, there is a significant obstacle for pediatric patients because of their rapid hepatic growth.
To ensure stable G6PC expression despite early intervention, the lab is working on a novel concept
for a gene therapy vector that introduces a functional copy of G6Pase-α into a designated location
without disturbing other genetic information. We are hopeful that this new development will lead to
gene therapy for the infant and pediatric populations with GSD-Ia.
What is AAV8 mediated GSD 1a gene therapy?
It is a medical approach that uses a harmless virus to deliver and insert a corrected or therapeutic
gene (that is G6Pase-a enzyme for GSD-Ia) into a patient's cells. The AAV (adeno associated virus)
acts as a delivery vehicle, carrying the desired genetic material into the patient's cells so that they
can produce the missing or corrected G6Pase-a enzyme. There are several different kinds of AAV. In
the GSD-Ia case, we need to deliver the gene into the liver, so we use AAV8, because AAV8 is the
best for liver gene delivery.
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" ... because every child deserves to be healthy."