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NIAAA to Fund PGx for Alcoholism

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – The National Institutes of Health wants to fund studies aimed at personalizing drug treatments for alcoholism by using pharmacogenomic approaches and research into how genetic variation affects drug reactions.

Because recent research in human and animal models have discovered that genetic variation is “significantly” linked to the efficacy of drugs for treating alcoholism, the National Institute on Alcohol Abuse and Alcoholism plans to give out $2 million in 2011 for a range of research efforts in this area, according to NIH.

Because of the genetic heterogeneity between alcohol drinkers there is no one medication treatment that works in all patients, which has made it necessary to provide a menu of treatments that clinicians can use to find which ones work.

A personalized treatment approach that matches specific interventions to the individual, particularly to an individual’s genetic profile, is more efficient, according to NIAAA.

The studies funded under this grant program will aim to use human and animal studies that can help to determine the full range of genetic variation that affects the pharmacodynamic and pharmacokinetic parameters that result in altered drug efficacy and toxicity.

Although pharmacogenetic research for alcohol use disorders is in its early stages, NIAAA said in its request for applications that progress is being made in identifying genetically influenced pharmacodynamic variability for the efficacy and toxicity of alcohol medications.

One example of the potential and problems for these studies is a single-nucleotide polymorphism in the mopoid receptor gene that has been associated in two studies with the efficacy of naltrexone in reducing drinking. Because some other studies did not find the same effect, however, it is likely that there are other genetic and environmental factors involved in the reactions.

Another example is medication that targets parts of the serotonergic systems and which may be used for personalized alcohol treatments. The presence of the L versus the S allele on a serotonin transporter gene has been found to influence responses to the GlaxoSmithKline drug ondansetron. Alcoholics with the L-allele have greater alcohol craving than those with the S-allele, and polypmorphisms in another receptor result in differences in sensitivity to benzodiazepines, a first line medication to treat early stage alcohol withdrawal systems.

Researchers may apply for funding for a range of studies of AUDs, including efforts to: use information from genome-wide association studies to determine which genetic variations affect medication response; supplement clinical trials to collect genotype data; use deep-sequencing technologies to identify variations in candidate genes that may play a role in drug responses; use pharmacogenomic testing in diverse populations; develop pharmacogenomic tests to examine genetic variability in side effects from medication; use gene expression profiling to determine transcriptomics changes associated with drug response; perform expression and proteomic profiling in animal models; perform genomic mapping of drug response traits, and other related studies.