Gene Therapy Trial for Age-Related Macular Degeneration Now Open at Columbia

A phase 2 clinical trial is underway at Columbia University and NewYork-Presbyterian to test an investigational gene therapy for dry age-related macular degeneration, a progressive, chronic eye disease with no cure and a leading cause of blindness in the United States.

The first patient to receive the investigational therapy at Columbia—and the first to get the treatment in the tristate area—was treated in December 2020.

An estimated 11 million individuals in the United States and more than 190 million people worldwide have macular degeneration. The vast majority of patients are 65 or older and have the dry form of the disease, which slowly causes irreversible vision loss. As the U.S. population ages, it is estimated that by 2050 some 22 million Americans may experience vision loss due to macular degeneration. 

“Vision loss has a tremendous impact on the lives of patients and their families, but currently there are no FDA-approved treatments for dry macular degeneration,” says Tongalp Tezel, MD, the Chang Family Professor of Ophthalmology and director of the vitreoretinal service at Columbia University Vagelos College of Physicians and Surgeons and principal investigator of the trial at Columbia. “Any treatment that can slow or stop the progression of this disease would be immensely valuable to patients, many of whom continue to lead active lives well into their 80s or 90s.”

Scientists have discovered that age-related macular degeneration is linked to variants of complement, an ancient branch of the immune system. In 2005, a team of scientists led by Rando Allikmets, PhD, the Acquavella Professor of Ophthalmic Science in Ophthalmology and Pathology & Cell Biology at Columbia University Vagelos College of Physicians and Surgeons, was among the first to discover that a mutation in a gene that makes a complement protein triggers macular degeneration. Since then, several variants in complement genes have been associated with increased risk for age-related macular degeneration. 

How the investigational gene therapy works 

The investigational gene therapy (GT005) being studied in this trial uses a genetically modified viral vector to deliver DNA that encodes for complement factor I (CFI), a protein that prevents the immune system from attacking cells in the retina. GT005 is given as a single, one-time surgical injection underneath the retina.

“Gene therapies for other eye diseases exist, but this trial is the first to test the safety and effectiveness of a gene therapy for dry macular degeneration,” says Tezel, a clinician-scientist who also directs a retina research laboratory at Harkness Eye Institute at NewYork-Presbyterian/Columbia University Irving Medical Center. 

How the study works 

The clinical trial is testing the safety and efficacy of GT005 in people with dry age-related macular degeneration. 

Study participants will be followed for up to a year to determine if the therapy can slow the progression of geographic atrophy and monitor for side effects. 

GT005 has received fast-track designation from the U.S. Food and Drug Administration, which streamlines the review of drugs for serious conditions without FDA-approved treatment options, for the treatment of geographic atrophy secondary to dry age-related macular degeneration.

Treatment of genetic eye diseases at Columbia

Columbia ophthalmologists’ research into the genetics of eye diseases has led to a new clinic for patients with ophthalmic disorders of genetic origin.

In 2019, the department launched the Applied Genetics Service, an interdisciplinary program to identify, counsel, and treat individuals with genetic variations associated with ophthalmic disorders. “Thanks to this program, we have screened more than a thousand patients for various eye diseases, and multiple specialists review each case to determine the most appropriate care plan,” says George A. Cioffi, MD, the Jean and Richard Deems Professor of Ophthalmology, the Edward S. Harkness Professor of Ophthalmology, chair of the Department of Ophthalmology at Columbia University Vagelos College of Physicians and Surgeons, and ophthalmologist-in-chief at NewYork-Presbyterian/Columbia University Irving Medical Center.

“Many of our patients also are eligible for research studies and clinical trials at CUIMC and other locations, and it is our hope that the new program will lead to the development of new genetically based therapies for these conditions.”

The phase 2 gene therapy trial is part of Columbia’s Precision Medicine Initiative.