DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cholesteryl ester storage 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 moduleCholesteryl ester storage 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 cholesteryl ester storage 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.
Molecular view
lipase A, lysosomal acid type (LIPA) — LIPA 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6V7N · 2.62 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Cholesteryl ester storage disease (CESD) involves a severe deficiency of acid cholesteryl ester hydrolase and triglyceride lipase activity in liver, spleen, and lymph node, with the hydrolase also deficient in aorta. Tissue storage of both cholesteryl esters and triglycerides is generalised. The lipid and enzymatic changes are very similar to those in Wolman’s disease. A 2017 case report of a two-year-ten-month-old female with hepatomegaly, elevated liver enzymes, and dyslipidemia was diagnosed by liver biopsy, though the authors note that measuring enzyme activity is the gold standard for diagnosis.
A 2003 review of cholesteryl ester transfer protein (CETP) as a drug target states that CETP facilitates exchange of neutral lipids between HDL and apolipoprotein B containing lipoproteins. The question of whether CETP promotes or protects from atherosclerosis had not been answered at that time. Data on CETP as a marker were inconclusive and not useful for clinical decision making. A first clinical study of pharmacological inhibition of the protein proved effective in raising HDL cholesterol, which the review describes as promising.
A 1992 review on cholesteryl ester accumulation in atherosclerotic lesions covers transcytosis of lipoproteins, effects of platelets and PGI2 on endothelial transport, transformation of macrophages to foam cells, and cholesteryl ester deposition in extracellular space. It describes the development of monoclonal antibodies recognising atherosclerotic lesions and peroxidised lipoproteins.
No clinical trial has tested a drug that reverses the underlying enzyme deficiency in CESD. The CETP inhibitor studies cited are for atherosclerosis, not CESD. What is missing is any trial of enzyme replacement, gene therapy, or substrate reduction in patients with CESD, along with funding for such work and clear patient stratification by residual enzyme activity.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Clinical Investigation · 1972 · 128 citations · open access
Enzyme deficiency in cholesteryl ester storage disease
AbstractCholesteryl ester storage disease has been shown to involve severe deficiency of acid cholesteryl ester hydrolase and triglyceride lipase activity in liver, spleen, and lymph node. The cholesteryl ester hydrolase was also deficient in aorta. Tissue storage of both cholesteryl esters and triglycerides is generalized. Both the lipid and enzymatic changes are very similar to those in Wolman's disease.
Current Opinion in Lipidology · 2003 · 18 citations
Cholesteryl ester transfer protein: gathering momentum as a genetic marker and as drug target
AbstractPURPOSE OF REVIEW: Cholesteryl ester transfer protein facilitates the exchange of neutral lipids between HDL and apolipoprotein B containing lipoproteins, which hold powerful opposing roles as risk factors for coronary artery disease. The question as to whether cholesteryl ester transfer protein promotes or protects from atherosclerosis, however, has not been answered. RECENT FINDINGS: This review considers studies dealing with cholesteryl ester transfer protein variants and their effect on blood lipids in various metabolic and clinical settings. Other studies discussed deal with the association between the transfer protein and cardiovascular disease. Research on the biological activity of the cholesteryl ester transfer protein molecule is described including a first clinical study where pharmacological inhibition of the protein proved to be effective in raising HDL cholesterol. SUMMARY: Data concerning the potential marker role of cholesteryl ester transfer protein, although accumulating, are still inconclusive and, at present, not useful for clinical decision making. Inhibition of the protein was demonstrated to be feasible and appears to be promising.
LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) · 2017 · 3 citations · open access
IMPORTANCE OF LIVER BIOPSY IN THE DIAGNOSIS OF LYSOSOMAL ACID LIPASE DEFICIENCY: A CASE REPORT
AbstractABSTRACT Objective: To describe a case of cholesteryl ester storage disease (CESD) and discuss the importance of liver biopsy for diagnosis. Case description: A female patient, aged two years and ten months, presented with an increased abdominal volume following hepatomegaly for four months. Abdominal ultrasound demonstrated hepatomegaly and hepatic steatosis. Laboratory tests showed elevated liver serum enzymes and dyslipidemia. Liver biopsy was consistent with CESD. Comments: Although measuring enzyme activity is the gold standard for CESD diagnosis, liver biopsy is very helpful when investigating suspected cases of CESD, particularly upon other differential diagnoses to be considered.
Accumulation of Cholesteryl Ester in Atherosclerotic Lesions
AbstractThis article reviews aspects of the molecular pathology of cholesteryl ester accumulation in atherosclerotic lesions. 1. Transcytosis of lipoproteins through a cultured endothelial monolayer. 2. Effects of platelets and PGI2 on intercellular transport of endothelial cells. 3. Transformation of macrophages to foam cells. 4. Cholesteryl ester deposition in the extracellular space of atherosclerotic lesions. The development and use of novel monoclonal antibodies recognizing atherosclerotic lesions and peroxidized lipoproteins prepared from then are also discussed.
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.
