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Molecular genetic approach to treatment and diagnosis of alcohol and drug dependence

a genetic approach and alcohol and drug technology, applied in the direction of drug compositions, biochemistry apparatus and processes, nervous disorders, etc., can solve the problems of disulfiram having limited utility, nausea, vomiting, and hypertension

Inactive Publication Date: 2016-11-17
UNIV OF VIRGINIA ALUMNI PATENTS FOUND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is based on molecular genetics techniques that can predict which alcohol or drug dependent subjects will respond to specific treatments and which ones may have an adverse event. The invention also includes methods for determining whether a person has a predisposition to addictive disease, will be responsive to treatment, and identifying genetic markers indicative of a person's response to treatment. The invention can also be used to subtype groups of people with addictive diseases by biological or psychological measures to determine which treatment will be most effective for each individual.

Problems solved by technology

Patients who take disulfiram and drink alcohol experience an increased dilation of arterial and capillary tone producing hypotension, nausea, vomiting, flushing, headache and possibly in some, worse symptoms.
Nevertheless, recent research shows that disulfiram has limited utility because compliance is low unless it is administered by a partner or spouse.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

embodiments

[0122]The polymorphisms identified herein also include their related miRNA, mRNA, ncRNA, or protein expression, levels, or states of function, or other biochemical products or chemical associations, which may serve as biomarkers.

[0123]In an aspect, a method of treating an addictive disease or disorder is provided, comprising: administering to a patient in need thereof a therapeutically effective amount of an antagonist of the serotonin receptor 5-HT3, wherein the patient's serotonin transporter gene SLC6A4 is known to have at least one, including two, three, four, five or more, of rs1176719 (including the AA genotype), rs1150226 (including the AG genotype), rs17614942 (including the AC genotype), rs1042173 (including the TT genotype), rs1176713 (including the GG genotype), LL genotype of 5-HTTLPR, or any combination thereof. For example, the patient's serotonin transporter gene SLC6A4 is known to have rs1176719 and rs1150226; rs1176719, rs1150226 and rs17614942; rs1176719, rs1150226...

example 1

Analysis of Gene Patterns Related to Response to Ondansetron Treatment

[0370]Genotype data was collected from 281 patients participating in a clinical trial wherein ondansetron was administered. Epistatic analysis among SNPs from serotonin (SERT), 5HT-3A, and 5HT-3B reveal that significant epistatic effect exists among the three genes in affecting response to ondesetron treatment as measured by drinks / drinking day (DDD), drinks / day (DD), percentage heavy drinking days (PHDD), and percentage of days abstinent (PDA).

Combination of either 5-HTT (LL + TT) or rs1150226 (AG) orrs1176713 (GG)LL / TT or AG or GGOutcomes / Genotype combination(90 / 283 = 32%)ComparisonOND [40 / 133] vs. Placebo[50 / 139]Drinks per Drinking Days−1.77 [−2.94, −0.59](DDD)(0.003)Percentage of Heavy Drinking Days−11.60% [−22.49, −0.71](PHDD)(0.037)Percentage Days of Abstinent11.96% [1.11, 22.81](PDA)(0.031)Percentage of Subjects with No HeavyOdds RatioDrinking Days (PSNHDD)ComparisonOND [8 / 23] vs. Placebo [3 / 27]Last 1 month...

example 2

CART Analysis of Gene Patterns Related to Response to Ondansetron Treatment

[0371]A decision tree is a structure that can be used to divide up a large collection of records into successively smaller sets of records by applying a sequence of simple decision rules. One advantage of decision tree is that the results can be easily interpreted. CART is a popular decision tree algorithm first published in Breiman et al 1984. CART starts by dividing data into 2 sub-groups (child nodes) that are homogeneous with respect to a particular target variable, in our case the target variable is the binary class label Z. By doing exhaustive search over all possible cutoffs for all possible candidate covariates, sub-groups are formed by identifying optimal split point for the optimal candidate covariate. Repeat the process recursively at each child node until one of the stopping criteria is met. In the end, CART prunes tree to smaller optimal size using cross-validation. After the final tree is determ...

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PUM

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Abstract

The present invention provides compositions and methods useful for diagnosing, treating, and monitoring alcohol dependence and disorders and susceptibility to alcohol dependence disorders, as well as drug related dependence and disorders.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. application Ser. No. 13 / 606,271, filed Sep. 7, 2012, which is entitled to priority pursuant to 35 U.S.C. §119(e) to U.S. provisional patent application No. 61 / 532,781, filed on Sep. 9, 2011. The entire content of each are incorporated herein by reference in their entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]This invention was made with government support under Grant AA032903, AA001016, AA012964 and AA010522 awarded by the National Institutes of Health. The government has certain rights in the invention.BACKGROUND[0003]Alcohol abuse and dependence are widespread and it is estimated that 14 million American adults abused alcohol or were dependent on it in 1992 and that approximately 10% of Americans will be affected by alcohol dependence sometime during their lives. Alcohol dependence, characterized by the preoccupation with alcohol use, tolerance, and withdrawal, i...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/4178C12Q1/68
CPCA61K31/4178C12Q2600/156C12Q2600/106C12Q1/6883A61P25/30
Inventor JOHNSON, BANKOLE A.
Owner UNIV OF VIRGINIA ALUMNI PATENTS FOUND
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