Cold turkey

We are back from the Research Society on Alcoholism meeting brimming with new ideas. Conferences are always a fun time to show off your discoveries, get ideas for new projects and start up new collaborations with your friends and colleagues.  Some of our new ideas demanded our immediate attention (in part because our summer students needed projects), and we took a little hiatus from our blog to get those projects going in the lab.

Something we have not talked about in the development of new medicines, but is nonetheless important, is gene regulation.  It is commonly thrown around in every day media that we are born with (and die with) a set of genes that influence what we look like, our behaviors and our susceptibility to certain diseases. How this happens is that our genes provide the code for the proteins that make up our bodies.

What is important for drug development is the fact that gene expression is highly regulated. That is to say, which ones, how much and where in our body our genes are used to make protein is all under strict control. Not only can our genes influence our susceptibility to certain diseases but disease can also change how our genes are regulated.  New research indicates that targeting gene regulation seems to be a viable option for developing new treatments for disease.

One form of gene regulation is histone acetylation and deactylation. Histone acetylation allows genes to be transcribed and eventually used to make proteins while histone deactylation prevents this from happening. Histone deactylase (HDAC) inhibitors are a type of drug that tips the scales in favor of the former process, that is, allowing genes to be used to make proteins. One example in which this form of gene regulation has been targeted for disease treatment is for alcohol dependence.

For people addicted to alcohol and in animal models of alcohol abuse, going cold turkey on booze produces a number of withdrawal symptoms. These symptoms can be alleviated by alcohol and are a large component of what drive people to drink again. One of these symptoms is extreme anxiety.  During withdrawal, HDAC activity in the brain increases and the production of a protein called neuropeptide Y decreases. These effects of alcohol withdrawal can be treated by an HDAC inhibitor called trichostatin A . Trichostatin A treatment decreases HDAC activity and increases NPY production during withdrawal. More importantly, this treatment reduces withdrawal-induced anxiety.

Much more research needs to be done to better understand how genes are regulated normally and in diseased states.  This area of research will bring a promising new class of drug treatments.