UC Davis Health Tests Experimental Gene Therapy for Wet AMD

UC Davis Health Tests Experimental Gene Therapy for Wet AMD

August 31, 2023

Ophthalmologists at UC Davis Health used an experimental gene therapy to address wet age-related macular degeneration (wet AMD) in a patient. This marked the UC Davis Eye Center's first use of gene therapy.

The treatment formed a component of a phase 3 clinical study, employing a randomized, partially masked, controlled approach, to assess the efficacy and safety of ABBV-RGX-314, an experimental therapy, for wet AMD. UC Davis Health is among 93 U.S. sites engaged in this clinical trial.

This investigative treatment lacks FDA approval, and both its effectiveness and safety remain have yet to be established. Wet AMD, a leading cause of vision loss among older adults, impacts about 2 million individuals in the U.S., Europe, and Japan.

"The current treatments for wet AMD may be life-long, and injections can be as frequent as every month," said Glenn Yiu, professor of ophthalmology at UC Davis Health and principal investigator for the new clinical trial. "If approved, a gene therapy solution has the potential to maintain vision while reducing the number of injections, by allowing the eye to continuously produce the medicine on its own," Yiu said.

What Is AMD and Wet AMD?

AMD leads to damage in the macula, a pivotal area in the eye's lining responsible for clear vision. Consequently, central vision blurs, making tasks like driving and reading challenging. An early indicator of wet AMD is the distortion and waviness of straight lines.

In the case of wet or neovascular AMD, abnormal blood vessels develop beneath the retina, resulting in bleeding or fluid leakage at the rear of the eye, causing vision deterioration. This process, termed "neovascularization," is predominantly triggered by vascular endothelial growth factor (VEGF), a growth factor.

Management of wet AMD hinges on repetitive eye injections of drugs that obstruct VEGF, targeting the affected area.

Gene Therapy May Offer Different Approach

Unline stem cell therapies, which involve introducing regenerative cells into the eye, gene therapy uses an empty viral envelope, a vector, to convey a gene containing specific genetic instructions to create proteins. ABBV-RGX-314, for instance, carries instructions to synthesize anti-VEGF proteins, allowing the eye to independently produce the medication after a single injection.

In July, Yiu led the inaugural experimental gene therapy eye surgery at UC Davis Health. This intricate procedure surpasses the simplicity of monthly injections, involving a vitrectomy to replace the eye's gel with saline infusion before introducing the gene therapy vector beneath the retina.

Over the following months, Yiu will assess the need for ongoing monthly anti-VEGF injections in the participant.

Paul Sieving, formerly directing the National Eye Institute, now holds the position of ophthalmology professor at UC Davis Health. His establishment of the Center for Ocular Regenerative Therapy (CORT) underscores the institution's commitment to advancing cell and gene therapies.

"It is noteworthy for patients in Northern California that UC Davis Health is doing experimental ocular gene therapy studies in the Department of Ophthalmology and Vision Sciences. What excites me most about this is the potential of Dr. Yiu's work to reduce the repeated eye injections currently required for wet age-related macular degeneration," Sieving said.

UC Davis Health has currently enlisted three patients for the clinical trial and intends to expand enrollment further. Those aged between 50 and 88, diagnosed with wet AMD and having received previous anti-VEGF injections, may meet the criteria for participation.