Dopamine Gene Variants Predict Response to Aripiprazole in Individuals

Description:

Technology: Since medications that can control, regulate, or change the brain dopamine system might be beneficial in treating Alcohol Use Disorder (AUD), MUSC investigators studied the anti-drinking effect of a marketed brain dopamine acting medication, aripiprazole, in individuals with AUD who were genotyped for variants in several brain-functional dopamine system genes including: the dopamine transporter gene (DAT1) variable nucleotide tandem repeat (VNTR 9R vs. 10R), the dopamine 4 receptor (DRD4) long (>7) vs, short (<7) VNTR’s), catechol-o-methyl transferase (COMT) (val158met SNP), and a dopamine D2 receptor SNP (rs 1076560). They found that the DAT1 genotype is most critical for the amount of drinks in non-treatment seeking individuals. In addition, an additive effect was found with additional gain of function dopamine alleles that demonstrate an added effect on the ability of aripiprazole to reduce drinking behavior (data not shown). As a whole, these brain dopamine system alleles can help inform AUD trials, guide development of new pharmacotherapies and be used as a diagnostic test to identify specific individuals that are most likely to benefit from dopaminergic based medications.

Overview: According to the National Institute for Alcohol Abuse and Alcoholism (NIAAA), 6.2 percent of adults in the US had an alcohol use disorder (AUD) in 2015. Medications available to treat AUD are not universally efficacious and in group studies have small to moderate effect sizes. Dopamine is one neurotransmitter thought to play a crucial role in the development and maintenance of AUD. Within the dopamine system there are a number of putative functional genetic variants influencing its production in the brain including receptor binding, synaptic abundance, breakdown, and that potentially might predict medication response. Clinical trials of dopaminergic medications, including the dopamine partial agonist aripiprazole (APZ), have been mixed, and positive effects highly variable. This suggests that genetic diversity may influence the effectiveness of dopaminergic medications for AUD and other conditions.  

Applications: Companion diagnostic, informing AUD treatment and AUD clinical trials, drug discovery.

Advantages:  Determine groups more likely to respond to dopaminergic compounds for multiple applications, including AUDs Key Words: AUD, alcohol use disorder, alcoholism, pharmacotherapy, aripiprazole, D2, DRD4. COMT, DAT1, SLC6A3, dopamine system, dopaminergic partial agonist, alcohol, addiction

Key Words: AUD, alcohol use disorder, alcoholism, pharmacotherapy, aripiprazole, D2, DRD4. COMT, DAT1, SLC6A3, dopamine system, dopaminergic partial agonist, alcohol, addiction

 

Background Publication:

Anton RF et al., (2008). A randomized, multicenter, double-blind, placebo-controlled study of the efficacy and safety of aripiprazole for the treatment of alcohol dependence. J Clin Psychopharmacol, 28(1):5-12.

 

Inventors: Ray Anton and Joe Schact       

Patent Status:  US utility filed 6.23.18                       

MUSC-FRD Technology ID: P1754       

 

 

Patent Information:
Category(s):
Diagnostic
For Information, Contact:
Scott Davis
Sr Licensing Manager
MUSC Foundation for Research Development
843-876-1900
davissco@musc.edu
Inventors:
Raymond Anton
Joseph Schacht
Keywords:
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