Mayo Clinic. US: In an international study, Mayo Clinic researchers and
collaborators have identified genetic markers that may help in
identifying individuals who could benefit from the alcoholism treatment
drug acamprosate (Campral). The findings, published in the journal Translational Psychiatry,
show that patients carrying these genetic variants have longer periods
of abstinence during the first three months of acamprosate treatment.
Acamprosate
is a commonly prescribed drug used to aid patients in recovery from
alcoholism. Mayo researchers studied the association between variation
in candidate genes and the length of sobriety in alcohol-dependent
patients treated with acamprosate in community-based programs. They
found that, when other environmental and physiological factors were
considered, patients with the common allele of the genetic variant
rs2058878 located in the GRIN2B gene, stayed sober more days
than those with a variant allele of the same polymorphism. This finding
was replicated in a sample of alcohol-dependent patients treated with
acamprosate in a study conducted by collaborators from Germany.
“This association finding is a first step towards development of a
pharmacogenetic test allowing physicians to choose appropriate treatment
for specific subgroups of alcohol-dependent patients,” says Victor Karpyak, M.D., Ph.D.,
Mayo Clinic psychiatrist and lead author of the article. “We believe
that individualized treatment selection will eliminate the need for
trial-and-error approaches and improve treatment efficacy in patients
with alcohol use disorders.”
The Mayo findings support evidence implicating an important role of the N-Methyl-D-aspartate
(NMDA) receptors in the treatment effects of acamprosate. The
researchers say more studies are needed to determine potential
importance of identified genetic variants in the longer-term effects of
acamprosate, as well as the molecular and physiological mechanisms
behind the drug’s action.
The study was funded in part by the Mayo Clinic Center for Individualized Medicine;
the SC Johnson Genomics of Addiction Program at Mayo Clinic; the
National Institutes of Health; the National Center for Advancing
Translational Sciences; the National Genome Research Network of the
German Federal Ministry of Education and Research; the Bundesministerium
für Bildung und Forschung; and the Alfred Krupp von Bolen und
Halbach-Stiftung (Foundation).
Other authors include J. M. Biernacka, Ph.D., Jennifer Geske, G.D.
Jenkins, J.M. Cunningham, Ph.D., A.A. Leontovich, Ph.D., O.A. Abulseoud,
M.D., Daniel Hall-Flavin, M.D., L.L. Loukianova, M.D., Ph.D., T.D.
Schneekloth, M.D., M.K. Skime, Richard Weinshilboum, M.D., Mark Frye,
M.D., and D.S. Choi, Ph.D., of Mayo Clinic; J. Ruegg, Karolinska
Institutet; O. Kononenko, Uppsala University; J. Frank, M.D., M.
Rietschel, M.D., F. Kiefer, M.D., and K. F. Mann, M.D.,
Mannheim-Heidelburg University; and M.M. Nöthen, M.D., University of
Bonn.