Epigenetics has been a hot topic at this year's meeting. When I ducked out of a symposium devoted to it on Saturday afternoon to catch another talk, by the time I got back the room was jam packed and a convention center employee was turning people away. "If the fire marshal comes we'll be in big trouble," she said.
There was only slightly more elbow room at this afternoon's press conference, where half a dozen researchers described their recent work investigating the possible roles of epigenetic mechanisms in everything from learning and memory to problems such as obesity, drug addiction and anxiety.
In a nutshell, epigenetics means altering gene expression without messing with DNA sequences. It includes DNA methylation, a chemical alteration to DNA that prevents genes from being read out to make proteins, and histone deacetylation, which accomplishes the same thing by keeping DNA strands tightly wound around spool-like histone proteins. Epigenetics has been a growing area of exploration in cancer biology over the last 20 years. Drugs that inhibit histone deacetylation, for example, have shown promise as cancer-fighting drugs.
Relatively little is known about the role of epigenetic mechanisms in the brain, but researchers described several intriguing findings at the press conference. Among them:
Tania Roth of the University of Alabama, Birmingham reported that rats exposed to early life stress exhibited abnormal DNA methylation that lasts into adulthood and reduces expression of the gene for an important growth factor in the amygdala, a hub of emotional processing in the brain.
Tracy Bale of the University of Pennsylvania in Philadelphia presented findings suggesting that high-fat diets during pregnancy can increase the body size of subsequent generations via epigenetic mechanisms in mice.
Quincey LaPlant of Mount Sinai School of Medicine in New York City described evidence that exposure to cocaine alters gene expression in reward pathways in the rodent brain via epigenetic mechanisms.
In the final presentation, Michael Ahlijanian of EnVivo Pharmaceuticals in Watertown, Massachusetts described the cognitive enhancing effects of an compound called EVP-0334. The drug inhibits histone deacetylation, and Ahlijanian and colleagues have found that it improves short- and long-term memory in standard lab tests with mice. But Ahlijanian raised a few eyebrows when he said EnVivo hopes to soon begin a phase I clinical trial with EVP-0334 to assess its safety in healthy volunteers (ultimately the team hopes it might restore memory in Alzheimer's patients). After all, it's not known what genes are affected and how permanently their activity is altered. "We don't think we're globally changing gene expression with this molecule," Ahlijanian said, but he added that something like 5% of genes might be affected. Mice given high doses of the drug for 28 days suffer no ill effects, he said. Well, I guess that's encouraging. But given the lasting effects described in some of the other talks and all the unanswered questions, I know one guy who's not quite ready to swallow that pill.
--Greg Miller
There was only slightly more elbow room at this afternoon's press conference, where half a dozen researchers described their recent work investigating the possible roles of epigenetic mechanisms in everything from learning and memory to problems such as obesity, drug addiction and anxiety.
It would appear that this would have significant application to treatment of alergies, asthma, arthritis and other inflamitory diseases as this technology could be used to manage the body's reaction to the irritants.