Wet or dry, hope for the eye

Tufts researchers find protein CD59 is key to slowing age-related macular degeneration

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BOSTON—A new in-vivo study by researchers at the Tufts University School of Medicine has demonstrated for the first time that the protein CD59, delivered by a gene therapy approach, significantly reduced the uncontrolled blood vessel growth and cell death typical of age-related macular degeneration (AMD), which results in the loss of sharp, central vision and is the most common cause of blindness in the elderly.

Led by principal investigator Dr. Rajendra Kumar-Singh, the study, "A Non Membrane-Targeted Human Soluble CD59 Attenuates Choroidal Neovascularization in a Model of Age Related Macular Degeneration," was published online April 28 in PloS ONE.

In their abstract, the authors state that approximately 10 percent of AMD patients suffer from an advanced form of the condition characterized by choroidal neovascularization (CNV). The study provides hope for nearly 2 million Americans suffering from a loss of vision due to AMD.

"CD59 is a naturally occurring protein found on the surface of human cells," Kumar-Singh states in the study. "Soluble CD59 is a modified version of this protein in that it no longer binds to cell membranes—but instead, is secreted and can act at distant sites. CD59 is also 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."

When pores or holes appear in the cell membranes, the condition is called "membrane attack complex" or MAC, the research states. CD59 is also known to block the formation of MAC.

Kumar-Singh explains that researchers delivered CD59 to the eyes of established mouse models with AMD, using a deactivated virus similar to one previously shown to be safe in humans. Researchers found that the mice eyes, treated with CD59, had 62 percent less uncontrolled blood vessel growth and 52 percent less MAC than controls did.

Co-first author Siobhan Cashman, a member of Kumar-Singh's lab, states in the study that 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, thus allowing for a safer and more convenient route of administration of treatment."

Co-first author Kasmir Ramo, a research technician, believes that while CD59 has significant potential as a treatment for AMD, the gene therapy approach could also be applied to other eye and systemic disorders.

AMD is the No. 1 cause of visual impairment among Americans age 60 and older. About 10 percent suffer from a condition called wet AMD because of the tears or fluid that spills from the eyes. Wet AMD is the more serious form, with more than 200,000 people in the U.S. diagnosed every year, according to the American Society of Retina Specialists. Like dry AMD, without treatment, patients can lose their central vision over time, leaving only peripheral or side vision. The symptoms can occur suddenly or gradually over time.

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 it would allow patients to be treated less frequently, reducing patient discomfort and lowering the chances of infection and other side effects associated with frequent injections into the eye.

Kumar-Singh notes, 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.

"This is the first study to find that soluble CD59 can function in vivo in any disease model, including age-related macular degeneration," Siobhan E. Gallagher, associate director of public relations at Tufts, tells ddn. "The key to the researchers' success was the use of a gene therapy approach that continuously produces soluble CD59 in tissues where it is needed. Our next step is to raise the capital needed to perform the toxicology studies that will enable us file an investigational new drug application with the U.S. Food and Drug Administration in order to examine the safety of soluble CD59 in human eyes."

In order to advance this study to Phase I clinical trials, the Tufts researchers have formed a partnership with Hemera Biosciences Inc. to raise private venture capital. Hemera Biosciences was co-founded in 2010 by Kumar-Singh and three retina specialists: Drs. Jay Duker, Elias Reichel and Adam Rogers, all of Tufts. The company states on its website that its primary mission is "to develop anti-complement gene-based therapies for the treatment of dry and wet AMD."

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