DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for non-alcoholic steatohepatitis — screening already-approved drugs against its 47-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNon-alcoholic steatohepatitis maps to a 47-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 non-alcoholic steatohepatitis 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
phosphodiesterase 6D (PDE6D) — PDE6D 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 6rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4JV8 · 1.45 Å · ligand (6R)-6-(pyridin-2-yl)-5,6-dihydrobenzimidazo[1,2-c]quinazoline (1M1). Experimental structure, not a prediction.
What the evidence adds up to
In a 2018 study of 178 patients with non-alcoholic fatty liver disease, those who consumed up to 20 g of ethanol per day had significantly lower ballooning and fibrosis scores on liver biopsy than non-drinkers, though steatosis and inflammation scores did not differ between groups. Gene expression analysis in the light alcohol group showed marked inhibition of immune response pathways, and the authors concluded that light alcohol consumption might suppress non-alcoholic steatohepatitis activity by reducing immune-related gene expression, associated with less liver fibrosis and hepatocellular injury. No survival or response rate data were reported.
A 2020 review notes that several molecules for NASH are in development but that reported efficacy to date has been limited. It argues that because NASH pathophysiology is complex, engaging multiple targets and pathways will be needed to improve pharmacological results, providing a rationale for combination therapy. The review discusses advantages and limitations of this approach but provides no new clinical data.
A 2013 review emphasises that alcoholic steatohepatitis and non-alcoholic steatohepatitis, despite similar histopathology and a shared role for innate immunity, have disease-specific mechanisms downstream of Toll-like receptor 4 and differential inflammasome involvement, making them distinct biological entities. It calls for further studies to dissect these emerging differences.
What is still missing are large, randomised trials that test specific combination regimens head-to-head against monotherapy and placebo, with histological endpoints and long-term follow-up. The 2018 alcohol finding is observational and confounded by self-selection; it does not establish causation or a safe dose for NASH patients. No drug has yet shown convincing efficacy in phase 3 trials, and patient stratification by genetic, metabolic, or inflammatory subtype remains unvalidated. Funding for adequately powered trials and biomarker development is lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Gut · 2020 · 196 citations · open access
Combination therapy for non-alcoholic steatohepatitis: rationale, opportunities and challenges
AbstractNon-alcoholic steatohepatitis (NASH) is becoming a leading cause of cirrhosis with the burden of NASH-related complications projected to increase massively over the coming years. Several molecules with different mechanisms of action are currently in development to treat NASH, although reported efficacy to date has been limited. Given the complexity of the pathophysiology of NASH, it will take the engagement of several targets and pathways to improve the results of pharmacological intervention, which provides a rationale for combination therapies in the treatment of NASH. As the field is moving towards combination therapy, this article reviews the rationale for such combination therapies to treat NASH based on the current therapeutic landscape as well as the advantages and limitations of this approach.
Light alcohol consumption has the potential to suppress hepatocellular injury and liver fibrosis in non-alcoholic fatty liver disease
AbstractBACKGROUND & AIMS: The modest consumption of alcohol has been reported to decrease the incidence of fatty liver or prevalence of steatohepatitis. In this study, we investigated the effect of light alcohol consumption on liver function and gene expression in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: The study group was formed of 178 patients diagnosed with non-alcoholic fatty liver disease, subclassified into two groups for analysis based on the daily alcohol consumption: non-alcohol group and light alcohol consumer group (≤20 g of ethanol/day). Clinical characteristics, liver histological features, gene expression, comprehensively analyzed using microarrays (BRB-Array tools), and molecular network were evaluated and compared between the two groups. RESULTS: No significant differences in steatosis or inflammation score were noted among the groups. However, the ballooning and fibrosis scores were significantly lower in the light alcohol consumer group than in the non-alcohol group. Gene expression analysis revealed a marked inhibition of the pathways involved in the immune response in the light alcohol group compared to that in the non-alcohol group. CONCLUSIONS: Light alcohol consumption might suppress activity of non-alcoholic steatohepatitis by reducing gene expression levels involved in the immune response. This inhibition in gene expression was associated with a lowering of liver fibrosis and hepatocellular injury.
Journal of Gastroenterology and Hepatology · 2013 · 33 citations · open access
Differences in innate immune signaling between alcoholic and non‐alcoholic steatohepatitis
AbstractThe similar histopathological characteristics of alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH), and the crucial role of the innate immune response in both conditions may lead to the assumption that ASH and NASH represent the same pathophysiological entities caused by different risk factors. In this review paper, we elaborate on the pathophysiological differences between these two entities and highlight the disease-specific involvement of signaling molecules downstream of the Toll-like receptor 4, and the differential mechanism by which the inflammasome contributes to ASH versus NASH. Our findings emphasize that ASH and NASH have disease-specific mechanisms and therefore represent distinct biological entities. Further studies are needed to dissect the emerging differences in pathogenesis of these two conditions.
Open Access CRIS of the University of Bern · 2020 · 0 citations · open access
Combination therapy for non-alcoholic steatohepatitis: rationale, opportunities and challenges.
AbstractNon-alcoholic steatohepatitis (NASH) is becoming a leading cause of cirrhosis with the burden of NASH-related complications projected to increase massively over the coming years. Several molecules with different mechanisms of action are currently in development to treat NASH, although reported efficacy to date has been limited. Given the complexity of the pathophysiology of NASH, it will take the engagement of several targets and pathways to improve the results of pharmacological intervention, which provides a rationale for combination therapies in the treatment of NASH. As the field is moving towards combination therapy, this article reviews the rationale for such combination therapies to treat NASH based on the current therapeutic landscape as well as the advantages and limitations of this approach.
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.
