Eye On the Cure Research News

Nov 7, 2019

AGTC Announces Development of Stargardt Disease Gene Therapy

Dual-vector delivery system designed to deliver the large ABCA4 gene

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Applied Genetic Technologies Corporation (AGTC), a biotechnology company developing gene therapies for retinal degenerative diseases and other conditions, has expanded its treatment development pipeline to include a gene therapy for Stargardt disease caused by mutations in the gene ABCA4.

Gene therapy development for Stargardt disease has been challenging because adeno-associated viruses (AAVs), the human-engineered viruses currently used for emerging retinal-disease gene therapies, don’t have the capacity for the ABCA4 gene which is relatively large.

AGTC’s emerging Stargardt disease gene therapy uses dual-vector AAV technology, which delivers the ABCA4 gene in two halves. When the halves are delivered to the recipient’s photoreceptors, they recombine to produce a whole, fully functional ABCA4 gene.

We are very pleased to see this potential treatment move toward a human study. If successful, this could pave the way for delivery of other genes that are currently too large to deliver using the common AAV-based gene-augmentation technology.

Brian Mansfield, PhD, executive vice president of research and interim chief scientific officer, Foundation Fighting Blindness

The dual-vector delivery system is based on technology developed by William Hauswirth, PhD, University of Florida, one of the foremost developers of retinal-disease gene therapies, and his colleagues at the University of British Columbia. Their dual-vector AAV successfully and safely delivered  functional ABCA4 genes to large animals. The proof-of-concept work is an important milestone for advancing the emerging treatment into a clinical trial. The collaborators’ large-animal study was published recently online in the journal Human Gene Therapy.

“AGTC’s announcement of their Stargardt disease gene therapy development and the success of Dr. Hauswirth’s large-animal study for ABCA4 gene delivery are exciting advancements for people with Stargardt disease,” says Brian Mansfield, PhD, executive vice president of research and interim chief scientific officer at the Foundation Fighting Blindness. “We are very pleased to see this potential treatment move toward a human study.  If successful, this could pave the way for delivery of other genes that are currently too large to deliver using the common AAV-based gene-augmentation technology.”

The leading cause of inherited macular degeneration, Stargardt disease affects approximately 30,000 people in the US. While the age of onset and severity for the condition can vary, Stargardt disease is often diagnosed in children and young adults, causing progressive central vision loss.

AGTC recently reported encouraging results for its gene therapy clinical trials for X-linked retinitis pigmentosa (RPGR mutations) and achromatopsia (CNGB3 and CNGA3 mutations).

The company also has a dry age-related macular degeneration gene therapy and optogenetic treatment in its preclinical pipeline.