This article goes along with: From Genetics to Epigenetics: Seeking to Identify How Environmental Triggers May Cause Brain and Behavior Disorders
From The Quarterly, Summer 2012
Although Dr. Akbarian concedes that we are still in the ‘early days’ of the effort to understand how patterns of epigenetic marks correlate with mechanisms of pathology in illnesses like autism and schizophrenia, he and others have already begun to explore how epigenetic knowledge can translate into new treatments.
“If we can understand very precisely the ‘risk-landscape’ in individual patients,” he says, “my hope is that we can use this information to design better treatments.” There is already a strong precedent for this kind of approach, he notes. With the comparatively deep knowledge scientists have acquired over the last 10-15 years in cancer biology, it is already established procedure to test certain subsets of patients for the presence of particular gene mutations for which targeted treatments have been developed. For instance, women with breast cancer are routinely tested for the presence of the so-called HER-2 mutation, whose presence or absence influences treatment decisions.
Dr. Akbarian has in mind a risk assessment of patients with brain and behavior disorders that might combine the insights of genetics and epigenetics. It will take some years before knowledge of the nervous system, and especially the brain and its complex neural networks, is extensive enough to support this approach. But his research and that of other neuroscience labs is beginning to paint a picture of what Dr. Akbarian calls ‘a risk constellation' that stitches together knowledge about places in the genome and epigenome where abnormalities correlate with pathology.
One very exciting, although still very new concept now being explored by Dr. Akbarian’s team is the use of various methods to target the enzymes that carry epigenetic marks to DNA (and the histones, which are proteins that are attached to it), and those which remove them. Epigenetic marks—chemical groups, such as CH3 (methyl groups)—are constantly being added and subtracted from the DNA letters that make up our genome.
Enzymes that add methyl groups to DNA are called methylases; enzymes that remove methyl groups from DNA are called demethylases. The object of a potential therapy might be to either add or subtract a methyl group at a particular position or positions in the genome, where research suggests doing one or the other would reverse an abnormality found to promote or be directly involved in disease pathology. This is not far-fetched by any means; a class of drugs called HDAC inhibitors have long been used as mood stabilizers in psychiatry. These drugs prevent an enzyme called deacetylase from removing epigenetic marks called acetyl groups.