DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for alcohol abuse — screening already-approved drugs against its 10-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAlcohol abuse maps to a 10-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for alcohol abuse is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
alcohol dehydrogenase 1C (class I), gamma polypeptide (ADH1C) — ADH1C is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet naddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1U3W · 1.45 Å · ligand NICOTINAMIDE-ADENINE-DINUCLEOTIDE (NAD). Experimental structure, not a prediction.
What the evidence adds up to
Genetic influences account for approximately 40% to 60% of the risk for alcohol abuse and dependence, according to a 2000 review. A 1999 family study contributed data from 1,214 members of 105 pedigrees, each containing three or more individuals affected with alcoholism. Over 160 genes have been individually assessed in relation to ethanol consumption, and nine microarray papers have identified 600 novel gene transcripts that may contribute to alcohol abuse. However, functional genomic experiments have failed to identify a single alcoholism gene. A 2015 study of 548 male inpatients with alcohol dependence found that polymorphisms of the dopamine-beta-hydroxylase gene modulate the trajectory of dependence: in carriers of the DBH*444 G/G genotype, alcohol withdrawal syndrome developed within two years in 22.5% of patients, compared with 8.11% of A/A carriers.
Clinical examination provides greater diagnostic accuracy than laboratory tests for detecting alcohol abuse. A 1986 study of 131 outpatients with alcohol problems, 131 social drinkers, and 52 family practice patients reported overall diagnostic accuracy of 85–91% for clinical signs, 84–88% for medical history items, and 71–83% for laboratory tests. A probability of alcohol abuse exceeding 0.90 was found if four or more clinical signs or four or more medical history items from the alcohol clinical index were present.
There is no cure for alcohol dependence. As of 2010, only three medications were approved by the U.S. Food and Drug Administration: disulfiram, naltrexone, and acamprosate. A number of other agents have been investigated, including selective serotonin reuptake inhibitors, 5-HT receptor agonists and antagonists, dopamine receptor antagonists and agonists, a GABA(B) receptor agonist, and a cannabinoid-1 receptor antagonist. Some showed promising efficacy in initial clinical studies, but the authors stated that further randomised studies with larger samples are warranted to establish their efficacy and safety.
What is still missing are adequately powered randomised controlled trials for the many candidate drugs that have shown only initial promise, a validated single genetic target that could guide drug development, and a clear stratification of patients by genetic or clinical subtypes to match them to existing or experimental treatments.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal on Addictions · 2000 · 148 citations
Genetics of the Risk for Alcoholism
AbstractThis paper reviews the literature on the importance of genetic influences in the development of alcohol abuse and dependence (alcoholism). The alcohol use disorders are fairly typical of most complex genetic conditions in that multiple genetic influences combine together to explain approximately 40% to 60% of the risk. One useful approach for identifying specific genes related to alcoholism involves identifying a population in which known genetic factors are controlled and using genome scan and/or case-control, association approaches to search for specific genes. Several characteristics, or endophenotypes, have been identified as both genetically influenced and contributing toward the risk for alcoholism, including alcohol-metabolizing enzymes, the low level of response to alcohol, and electrophysiological measures. The potential importance of each of these characteristics is reviewed, and data relating to the search for specific genetic material for each endophenotype are presented. These findings are placed in the perspective of the impact that they are likely to have on both prevention and treatment efforts in the alcohol field.
Clinical versus laboratory detection of alcohol abuse: the alcohol clinical index.
AbstractTo determine reliable indicators of alcohol abuse a comprehensive set of clinical and laboratory information was acquired from three groups of subjects with a wide range of drinking histories: 131 outpatients with alcohol problems, 131 social drinkers, and 52 patients from family practice. Findings from clinical examination provided greater diagnostic accuracy than laboratory tests for detecting alcohol abuse. Logistic regression analysis produced an overall accuracy of 85-91% for clinical signs, 84-88% for items from the medical history, and 71-83% for laboratory tests in differentiating the three groups. Further analyses showed 17 clinical signs and 13 medical history items that formed a highly diagnostic instrument (alcohol clinical index) that could be used in clinical practice. A probability of alcohol abuse exceeding 0.90 was found if four or more clinical signs or four or more medical history items from the index were present. Despite recent emphasis on the laboratory diagnosis of alcohol abuse simple clinical measures seem to provide better diagnostic accuracy.
Alcohol and Alcoholism · 2004 · 46 citations · open access
ALCOHOL AND GENE EXPRESSION IN THE CENTRAL NERVOUS SYSTEM
AbstractAIMS: To describe recent research focusing on the analysis of gene and protein expression relevant to understanding ethanol consumption, dependence and effects, in order to identify common themes. METHODS: A selective literature search was used to collate the relevant data. RESULTS: Over 160 genes have been individually assessed before or after ethanol administration, as well as in genetically selected lines. Techniques for studying gene expression include northern blots, differential display, real time reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization. More recently, high throughput functional genomic technology, such as DNA microarrays, has been used to examine gene expression. Recent gene expression analyses have dramatically increased the number of candidate genes (nine array papers have illuminated 600 novel gene transcripts that may contribute to alcohol abuse and alcoholism). CONCLUSIONS: Although functional genomic experiments (transcriptome analysis) have failed to identify a single alcoholism gene, they have illuminated important pathways and gene products that may contribute to the risk of alcohol abuse and alcoholism.
Description of the genetic analysis workshop 11 collaborative study on the genetics of alcoholism
AbstractProblem 1 of Genetic Analysis Workshop 11 consists of data from a family study of the genetics of alcoholism and related traits contributed by the six centers making up the National Institute for Alcohol Abuse and Alcoholism sponsored by the Collaborative Study on the Genetics of Alcoholism (COGA). The family data included 1,214 members of 105 pedigrees ascertained for having three or more individuals affected with alcoholism. Data available to workshop participants included clinical phenotypes, personality measures, smoking behavior, event-related potentials, platelet monamine oxidase B activity, and a genome scan of 296 markers.
Current Pharmaceutical Design · 2010 · 24 citations
Identification of Molecular Targets Associated with Ethanol Toxicity and Implications in Drug Development
AbstractAlcohol dependence is a major disease burden of adults in modern society worldwide. There is no cure for alcohol dependence. In this study, we have examined the molecular targets of ethanol-induced toxicity in humans based on a systematic review of literature data and then discussed current and potential therapeutic targets for alcohol abuse and dependence. Using human samples with ethanol exposure, microarray analyses of gene expression have shown that numerous genes are up- and/or down-regulated by alcohol exposure. The ethanol-responsive genes mainly encode functional proteins such as proteins involved in nucleic acid binding, transcription factors, selected regulatory molecules, and receptors. These genes are also correlated with important biological pathways, such as angiogenesis, integrin signalling pathway, inflammation, wnt signaling pathway, platelet-derived growth factor signaling pathway, p53 pathway, epidermal growth factor receptor signaling pathway and apoptosis signaling pathway. Currently, only three medications were approved by the U.S. Food and Drug Administration (FDA) for the treatment of alcohol abuse and alcohol dependence, including the aldehyde dehydrogenase inhibitor disulfiram, the micro-opioid receptor antagonist naltrexone, and the N-methyl-D-aspartate (NMDA) receptor inhibitor acamprosate (oral and injectable extended-release formulations). In addition, a number of agents are being investigated as novel treatments for alcohol abuse and dependence. These include selective 5-HT reuptake inhibitors (e.g. fluoxetine), 5-HT(1) receptor agonists (e.g. buspirone), 5-HT(2) receptor antagonists (e.g. ritanserin), 5-HT(3) receptor antagonists (e.g. ondansetron), dopamine receptor antagonists (e.g. aripiprazole and quetiapine), dopamine receptor agonists (e.g. bromocriptine), GABA(B) receptor agonists (e.g. baclofen), and cannabinoid-1 (CB(1)) receptor antagonists. Some of these agents have shown promising efficacy in initial clinical studies. However, further randomized studies with larger samples are warranted to establish their efficacy and safety profiles in the treatment of alcohol dependence.
S S Korsakov Journal of Neurology and Psychiatry · 2015 · 1 citations
The 444G/A and -1021 C/T polymorphisms of the dopamine-beta-hydroxylase gene modulate the trajectory of alcohol dependence development
AbstractAIM: To study the influence of 444 G/A (rs 1108580) and -1021 C/T (rs 1611115) polymorphisms of the dopamine beta-hydroxylase (DBH) gene on clinical parameters of the trajectory of alcohol dependence. MATERIAL AND METHODS: Authors studied 548 male inpatients, of Slavic ethnicity, with ICD-10 diagnosis of «alcohol dependence» (F-10.2). RESULTS: The effects of DBH * 444 G/A on the rate of formation of alcohol withdrawal syndrome (AWS), and DBH *-1021C/T on the age of onset of alcohol abuse with significant role of the age of first alcohol use were identified. In 444 G/A GG carriers, the development of AWS was accelerated since the beginning of alcohol abuse compared with AA carriers (p=0.026), AG carriers occupied an intermediate position. In 22.5% of GG carriers, AWS developed within 2 years (AA: 8.11%, p=0.005; AG: 17.67%, p=0.04). According to the results of linear regression analysis, in AG carriers the alcohol abuse (p=0.037) and the AWS (p=0.049) developed earlier than in AA carriers if the first alcohol use occured at the age of about 15 years. Among -1021C/T genotype carriers who began to abuse alcohol at an early age (before 20 years), there were 23.45% patients with CC genotype and only 11.97% with a T allele (genotypes CT+TT) (p=0.03), but T carriers began to abuse alcohol earlier than others (p=0.05) if the first alcohol use occurred at the age of about 16 years. CONCLUSION: The results can be used to search for genetic markers for prognosis of alcohol dependence development.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
