CD59 Gene Therapy Shows Promise for Macular Degeneration
Author: Tufts University School of Medicine
Published: 2011/04/30 - Updated: 2026/01/25
Publication Details: Peer-Reviewed, Research, Study, Analysis
Category Topic: Blindness - Vision Loss - Related Publications
Contents: Synopsis - Introduction - Main - Insights, Updates
Synopsis: This research reports on a peer-reviewed study from Tufts University School of Medicine demonstrating that CD59 gene therapy significantly reduced the progression of age-related macular degeneration (AMD), the leading cause of blindness in elderly populations. The findings are particularly useful for the millions of older adults facing AMD, as the therapy showed a 62 percent reduction in abnormal blood vessel growth and 52 percent reduction in membrane attack complex formation when delivered through a deactivated virus vector. Unlike current standard treatments requiring monthly injections directly into the eye, this gene therapy approach could allow for less frequent treatment, which would substantially reduce patient discomfort, infection risk, and the burden of ongoing medical procedures for seniors and visually impaired individuals managing this progressive condition - Disabled World (DW).
Introduction
A gene therapy approach using a protein called CD59, or protectin, shows promise in slowing the signs of age-related macular degeneration (AMD), according to a new in vivo study by researchers at Tufts University School of Medicine.
Led by senior author Rajendra Kumar-Singh, PhD, the researchers demonstrated for the first time that CD59 delivered by a gene therapy approach significantly reduced the uncontrolled blood vessel growth and cell death typical of AMD, the most common cause of blindness in the elderly. The study was published on April 28 in PLoS ONE.
Main Content
Activation of the complement system, a part of the immune system, is responsible for slowly killing cells in the back of the eye, leading to AMD. Activation of this system leads to the generation of pores or holes known as 'membrane attack complex' or MAC in cell membranes. CD59 is known to block the formation of MAC.
"CD59 is unstable and hence previous studies using CD59 have had limited success. The gene therapy approach that we developed continuously produces CD59 in the eye and overcomes these barriers, giving us renewed hope that it can be used to fight the progression of AMD and potentially other diseases," said Kumar-Singh.
Kumar-Singh is associate professor in the department of ophthalmology at Tufts University School of Medicine (TUSM) and member of the genetics; neuroscience; and cell, molecular, and developmental biology program faculties at the Sackler School of Graduate Biomedical Sciences at Tufts.
Kumar-Singh and colleagues delivered CD59 to the eye using a deactivated virus similar to one previously shown to be safe in humans.
Using an established mouse model of age-related macular degeneration, they found that eyes treated with CD59 had 62 percent less uncontrolled blood vessel growth and 52 percent less MAC than controls.
"Treatment was effective when administered at a very specific location beneath the retina, but importantly, also when it was administered to the center of the eye. This finding is especially encouraging because it would allow for a safer and more convenient route of administration of treatment," said co-first author Siobhan Cashman, PhD, assistant professor in the department of ophthalmology at Tufts University School of Medicine and member of Kumar-Singh's lab.
The current standard treatment for some forms of AMD requires an injection directly into the eye approximately every four weeks.
According to Kumar-Singh, gene therapy approaches to treat AMD are especially attractive because they will allow patients to be treated less frequently, reducing patient discomfort and lowering chances of infection and other side effects associated with frequent injections into the eye.
The researchers, including co-first author Kasmir Ramo, BS, research technician, believe that while CD59 has significant potential as a treatment for AMD, the gene therapy approach lends itself for application also in other eye and systemic disorders where low-level activation of complement has been implicated.
"Prior to initiating human clinical trials, we will need to perform extensive preclinical toxicology studies. In order to advance this study to Phase I clinical trials, we have formed a partnership with Hemera Biosciences Inc. to raise private venture capital," said Kumar-Singh.
AMD, which results in a loss of sharp, central vision, is the number one cause of visual impairment among Americans age 60 and older. While treatments are available for wet AMD, they do not prevent the progression of dry AMD, the form that affects 90 percent of AMD patients. Kumar-Singh noted, however, that the current study in combination with a previously published study from his laboratory suggests that CD59 may be useful for the treatment of both the dry and wet forms of AMD.
Study Details and Funding
This study was supported by grants from The Ellison Foundation; the National Eye Institute, part of the National Institutes of Health; the Virginia B. Smith Trust and grants to the department of ophthalmology at TUSM from the Lions Eye Foundation and Research to Prevent Blindness.
Cashman SM, Ramo K, Kumar-Singh R. PLoS ONE. "A Non Membrane-Targeted Human Soluble CD59 Attenuates Choroidal Neovascularization in a Model of Age Related Macular Degeneration." Published online April 28, 2011.
Insights, Analysis, and Developments
Editorial Note: While this 2011 study represents a notable advancement in understanding how gene therapy might address the complement system's role in AMD, the fact that researchers have since partnered with commercial entities to advance toward human clinical trials suggests the initial promise remains compelling enough to warrant continued investigation. For those living with AMD - particularly the dry form affecting 90 percent of patients - the potential for less invasive, less frequent treatment could meaningfully change the trajectory of vision loss and quality of life in older age - Disabled World (DW).Attribution/Source(s): This peer reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally authored by Tufts University School of Medicine and published on 2011/04/30, this content may have been edited for style, clarity, or brevity.