A custom collaboration with: Quintiles
Much of tomorrow’s healthcare will depend on making sense of the genome and developing personal medicine around it. But some exciting and promising health R&D looks beyond genomics to mechanisms that control how genes behave—and farther still, to research that has nothing to do with genomics.
Researchers have long known that genes are not everything. Identical twins have the same genes but differ in many ways, and the older they get, the more they differ. That’s because living modifies how genes work.
These processes are often lumped under the heading “epigenetics”—mechanisms that change gene function by modifying DNA without altering its sequence of bases. One example is DNA methylation, in which a methyl group attaches to DNA, usually silencing a gene. The Food and Drug Administration has already approved a handful of drugs that work on epigenetic mechanisms. Vidaza, which treats blood cancer, is one; scores more are in clinical trials.
When we say “gene,” we usually mean DNA that codes for proteins. More than 90 percent of our DNA, however, makes noncoding RNA (ncRNA), which does not lead to proteins but can govern epigenetic events.
About a third of protein-coding genes are thought to be controlled by a type of ncRNA called microRNA (miRNA), just one of which can target a hundred different genes. Researchers see two future roles for miRNAs: as promising diagnostic markers with potential for classifying cancers, and as treatment for disease. Noncoding-RNA proponent John Mattick, of the Institute for Molecular Bioscience at the University of Queensland, St. Lucia, Australia, has observed that it may be both easier and more productive to adjust the epigenetic regulatory software—for example, ncRNAs—than to try to correct the hardware in the form of protein-coding genes.
“I see a huge future for the use of noncoding RNAs to direct epigenetic changes at specific loci, rather than the shotgun approach using drugs that target the generic enzymes involved, which can have system-wide effects,” says Mattick.
Brain disorders, especially those related to aging, are another major focus of research. “In 2025, we’ll be able to take a 50-year-old, put that person through a series of simple blood tests and brain scans and come up with a risk score that will tell that person whether they’re at low, medium or high risk for developing Alzheimer’s disease or some other degenerative dementia of old age,” says P. Murali Doraiswamy, who heads Duke University’s biological psychiatry division. He hopes there will also be strategies to lower their risk.
Doraiswamy sees two other trends in brain research likely to have an eventual impact on medicine. One is the use of functional magnetic resonance imaging in a way analogous to a treadmill test for the heart. This technology can map brain circuits to show whether different parts of the brain are working well together. The second is the study of the brain’s cognitive reserve capacity—its inherent ability to resist disease through the use of alternate circuits in the brain.