From extending lifespan to bolstering the immune system, the drug’s effects are only just beginning to be understood.
Editor's Choice in Physiology
August 1, 2011|
J. AMBATI, B. GELFAND, AND M. HANSON
H. Kaneko et al., “DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration,” Nature, 471:325-30, 2011. Free F1000 evaluation
Millions of people suffer from macular degeneration, an aging-associated disease that slowly destroys central vision. What causes it has long puzzled researchers, but now ophthalmologist Jayakrishna Ambati, at the University of Kentucky, and colleagues have found that sufferers lack an enzyme normally involved in the processing of microRNA, leading to an accumulation of double-stranded RNA and apoptosis in the retina’s pigmented epithelial cells.
Three years ago, while studying angiogenesis in the mouse eye, Ambati’s lab found that injecting short, double-helical fragments of RNA prevented new blood vessel growth. They then collected eyes of human patients who had suffered from macular degeneration, and, “to our surprise,” Ambati says, found “huge accumulations of RNA duplexes.”—specifically, double-stranded RNA transcripts of Alu repeats, mobile sequences scattered throughout the genome.
Ambati’s lab tested different RNA-processing enzymes, and found that DICER1, which cuts pre-miRNA into its functional form, was reduced in the eyes of human patients suffering from late-stage macular degeneration. The lack of DICER1 allowed Alu repeats to accumulate, impeding cell function and initiating cell death.
Preventing Alu accumulation with antisense drugs “offers hope for some kind of targeted therapy,” according to Orly Reiner of the Weizmann Institute of Science. Ambati has already carried out successful tests in primates, and is planning a clinical trial in a few months.