DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for fatty liver disease — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleFatty liver disease maps to a 1-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 fatty liver disease 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.
What the evidence adds up to
Non-alcoholic fatty liver disease (NAFLD) is a complex condition with an estimated global prevalence of 25%. A 2023 study identified a rare causal variant in the MTTP gene (c.1691T>C p.I564T) in a four-generation family with progressive NAFLD leading to cirrhosis, decompensation, and hepatocellular carcinoma in the absence of obesity or type 2 diabetes. Hepatocyte-like cells derived from a homozygote donor showed significantly lower microsomal triglyceride transfer protein activity and lower lipoprotein ApoB secretion than wild-type cells, despite similar levels of MTTP mRNA and protein. Cytoplasmic triglyceride accumulation in these cells triggered endoplasmic reticulum stress, secretion of pro-inflammatory mediators, and production of reactive oxygen species. This variant was not associated with the characteristic features of abetalipoproteinaemia.
A 2013 review noted that both innate and adaptive immune systems contribute to NAFLD development, with pathogen-associated and danger-associated molecular patterns activating pattern-recognition receptors that result in inflammation. A 2024 review of new drugs for metabolic dysfunction-associated fatty liver disease (MASLD) stated that some progress has been made in drug research and development but that there is still great space for exploration. The paper summarised reasons for the current clinical status and challenges in developing new drugs for MASLD.
No drug is mentioned in any of these abstracts. The 2023 study provides a cell model for studying disease pathways but does not test any intervention. The 2024 review does not name any specific drug candidate or report any clinical trial results. What is still missing is a drug candidate that has been tested in a clinical trial for this specific MTTP variant or for the immune-inflammatory pathways described, as well as patient stratification strategies that account for rare genetic causes of NAFLD.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Hepatology International · 2013 · 182 citations · open access
Immune and inflammatory pathways in NASH
AbstractImmune and inflammatory pathways have a central role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Both the innate and adaptive immune systems contribute to the development of NAFLD. Pathogen-associated molecular patterns and danger-associated molecular patterns are known to activate a variety of pattern-recognition receptors that result in inflammation. The key features of the immune system and inflammatory pathways in the development of NAFLD are discussed in this review.
Identification and characterisation of a rare MTTP variant underlying hereditary non-alcoholic fatty liver disease
AbstractBackground & Aims Non-alcoholic fatty liver disease (NAFLD) is a complex trait with an estimated prevalence of 25% globally. We aimed to identify the genetic variant underlying a four-generation family with progressive NAFLD leading to cirrhosis, decompensation, and development of hepatocellular carcinoma in the absence of common risk factors such as obesity and type 2 diabetes. Methods Exome sequencing and genome comparisons were used to identify the likely causal variant. We extensively characterised the clinical phenotype and post-prandial metabolic responses of family members with the identified novel variant in comparison with healthy non-carriers and wild-type patients with NAFLD. Variant-expressing hepatocyte-like cells (HLCs) were derived from human-induced pluripotent stem cells generated from homozygous donor skin fibroblasts and restored to wild-type using CRISPR-Cas9. The phenotype was assessed using imaging, targeted RNA analysis, and molecular expression arrays. Results We identified a rare causal variant c.1691T>C p.I564T (rs745447480) in MTTP , encoding microsomal triglyceride transfer protein (MTP), associated with progressive NAFLD, unrelated to metabolic syndrome and without characteristic features of abetalipoproteinaemia. HLCs derived from a homozygote donor had significantly lower MTP activity and lower lipoprotein ApoB secretion than wild-type cells, while having similar levels of MTP mRNA and protein. Cytoplasmic triglyceride accumulation in HLCs triggered endoplasmic reticulum stress, secretion of pro-inflammatory mediators, and production of reactive oxygen species. Conclusions We have identified and characterised a rare causal variant in MTTP , and homozygosity for MTTP p . I564T is associated with progressive NAFLD without any other manifestations of abetalipoproteinaemia. Our findings provide insights into mechanisms driving progressive NAFLD. Impact and Implications A rare genetic variant in the gene MTTP has been identified as responsible for the development of severe non-alcoholic fatty liver disease in a four-generation family with no typical disease risk factors. A cell line culture created harbouring this variant gene was characterised to understand how this genetic variation leads to a defect in liver cells, which results in accumulation of fat and processes that promote disease. This is now a useful model for studying the disease pathways and to discover new ways to treat common types of fatty liver disease.
[Clinical status and challenges of new drugs for metabolic dysfunction-associated fatty liver disease].
AbstractMetabolic dysfunction-associated fatty liver disease (MASLD) is a major public health problem that seriously affects human health. At present, some good progress has been made in the research and development of new drugs for MASLD, but there is still great space for exploration. This paper summarizes and analyzes the reasons in the current clinical status and challenges for the research and development of new drugs for MASLD.
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.
