Scientists from the United States and China have identified the first gene therapy directly associated with the onset of “dry” macular degeneration, one of the two forms of age-related macular degeneration (AMD).
The findings, published in the New England Journal of Medicine, based upon work with human and mice cells, centers on a specific immune system protein called TLR3. Although helpful in fending off illness when confronted with certain viral infections, this molecule, when routinely activated, was also found to raise the risk for “dry” macular degeneration by attacking infected retinal cells.
Therapy May Lead to Dry AMD
A multi-institutional research team – led by Kang Zhang, MD, Ph.D. professor of ophthalmology and human genetics at Shiley Eye Center at the University of California, San Diego, School of Medicine – has made two important discoveries related to AMD: one, the discovery of the first gene, as well as two, finding there could be adverse consequences, including blindness, if individuals who possess a particular variation of this gene are treated with an experimental therapy currently being tested for another form of AMD.
The treatment in question, known as “RNA interference,” or RNAi, works by “silencing” genes that bring about wet AMD. Unfortunately, the treatment appears to simultaneously activate TRL3 – resulting in a 60 percent spike in retinal cell death among mice and humans genetically susceptible to developing dry AMD. The result: RNAi may help protect against wet AMD while boosting the risk for dry AMD, the study authors said.
“This raises particular concerns regarding RNAi therapy for wet AMD,” Zang said. “But by establishing this link between the treatment for the wet form of AMD and the potential harmful effect on the dry form of the disease, we can perhaps better understand the mechanisms of both diseases.”AMD is the leading cause of blindness in adults over the age of 60, according to the U.S. National Eye Institute. The progressively worsening disease affects the macula portion of the eye, located in the center of the retina, which enables detailed vision.
Use of RNAi can have the inadvertent effect of suppressing TLR3’s protective role because it induces TLR3 activation. This activation signals other cells to increase their antiviral defense, in essence, sending a message to “kill” what are recognized as infected cells.
The discovery may have major preventive and therapeutic benefits, according to Hemin Chin, Ph.D., director of the ocular genetics program at the National Eye Institute. “Given its high prevalence in the United States and the world, finding effective prevention and treatment strategies for AMD is of critical importance. The finding represents a major advancement in our understanding of dry AMD, for which effective treatment is not yet available.”
