DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for sitosterolemia — 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 moduleSitosterolemia 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
approvedEzetimibeApproved drug
Structures already discussed alongside sitosterolemia in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
The structure of mouse AsterC (GramD1c) — Ezetimibe has a real, experimentally solved structure in complex with this target (PDB 8AXW, 1.6 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet h56drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8AXW · 1.6 Å · ligand Ezetimibe (H56). Experimental structure, not a prediction.
What the evidence adds up to
Sitosterolemia is a rare autosomal recessive disorder caused by mutations in ABCG5 or ABCG8, leading to elevated plant sterols in plasma and tissues. Cholesterol synthesis is very low due to HMG-CoA reductase deficiency, while intestinal absorption of plant sterols is increased and hepatic sterol removal is slow. Plasma cholesterol levels are often elevated but can be normal. Clinical features include xanthomas, premature vascular disease, and arthritis; adolescent boys and girls are susceptible to fatal cardiac events.
A 15-month-old Korean girl presented with severe hypercholesterolaemia (total cholesterol 675 mg/dL, LDL-C 540 mg/dL) and intertriginous xanthomas first noticed at 3 months while exclusively breastfed. A low-fat/low-cholesterol diet and cholestyramine therapy normalised her serum cholesterol within 2 months, and cholestyramine was tapered off. Xanthomas regressed and disappeared by age 3. Gas chromatography-mass spectrometry at age 3, when LDL-C was 118 mg/dL, showed a sitosterol level of 19.36 mg/dL. Direct sequencing of ABCG5 revealed compound heterozygous null mutations. An 11-month-old female infant developed linear xanthomas in ankle skin folds at around 6 months, with significantly elevated total cholesterol and LDL-C. Genetic testing identified a homozygous ABCG5 c.1166G>A (p.Arg389His) mutation, inherited from heterozygous parents. A 7-year-old girl with tuberous xanthomas is also reported.
Bile acid malabsorption mobilises body sterols for bile acid synthesis and dramatically lowers plasma and monocyte sterol concentrations, potentially halting atherosclerotic progression. Ezetimibe has been reported to produce an excellent response in a patient with sitosterolemia and haemolytic anaemia. The disorder should be suspected when hypercholesterolaemia responds unexpectedly well to dietary modification or bile acid sequestrant therapy. Delayed diagnosis can lead to cardiovascular disease and haematological abnormalities.
What remains missing is systematic data on long-term outcomes with current treatments, prospective trials comparing ezetimibe versus bile acid sequestrants, and any evidence that lowering plant sterols prevents cardiac events in this population. No randomised controlled trials exist, and patient numbers are too small to stratify by genotype or age at diagnosis.
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 Lipid Research · 1992 · 252 citations · open access
Sitosterolemia.
AbstractSitosterolemia is a rare inherited lipid storage disease characterized chemically by the accumulation of plant sterols and 5 alpha-saturated stanols in plasma and tissues. Very low cholesterol synthesis due to a deficiency of HMG-CoA reductase associated with increased intestinal plant sterol absorption and slow hepatic sterol removal are major biochemical features. Because cholesterol synthesis cannot up-regulate, bile acid malabsorption mobilizes body sterols for bile acid synthesis and dramatically lowers plasma and monocyte sterol concentrations and may halt the progression of the atherosclerotic process.
International Journal of Clinical Practice · 2008 · 67 citations
Long-term efficacy and safety of ezetimibe 10 mg in patients with homozygous sitosterolemia: a 2-year, open-label extension study
AbstractOBJECTIVE: To assess the long-term efficacy and safety profile of ezetimibe 10 mg/day in patients with homozygous sitosterolemia. METHODS: This was an extension of a multi-centre, randomised, double-blind, placebo-controlled base study in which patients with homozygous sitosterolemia and plasma sitosterol concentrations > 5 mg/dl were randomised 4 : 1 to ezetimibe 10 mg/day (n = 30) or placebo (n = 7) for 8 weeks. Patients who successfully completed the base study with > 80% compliance to study medication were eligible to enter two, successive, 1-year extension studies in which ezetimibe 10 mg/day was administered in an open-label manner. Patients remained on their current treatment regimen (e.g. bile salt-binding resins, statins and low-sterol diet) during the base and extension studies. Patients had to be off ezetimibe therapy for > or = 4 weeks prior to entering the first extension. Efficacy and safety/tolerability parameters were evaluated every 12 and 26 weeks in the first and second years respectively. The primary efficacy end-point was mean percentage change in plasma sitosterol from baseline to study end for the cohort of patients (n = 21) who successfully completed the second extension study. RESULTS: Treatment with ezetimibe 10 mg/day led to significant mean percentage reductions from baseline in plasma concentrations of sitosterol (-43.9%; p < 0.001), campesterol (-50.8%; p < 0.001), low-density lipoprotein (LDL) sterols (-13.1%; p < 0.050), total sterols (-10.3%; p < 0.050) and apolipoprotein (apo) B (-10.1%; p < 0.050). No significant changes from baseline were observed for lathosterol, high-density lipoprotein sterol, triglycerides or apo A-1. Maximal reductions in sitosterol and campesterol occurred within the first 52 weeks of treatment and were sustained for the duration of the study. For LDL sterol, total sterols and apo B, maximal reductions were achieved early (by weeks 4 or 16) and waned slightly through the remainder of the study. Overall ezetimibe 10 mg was well tolerated. CONCLUSION: In patients with homozygous sitoserolemia, long-term treatment with ezetimibe 10 mg/day for 2 years was effective in reducing plasma plant sterol concentrations with an overall favourable safety and tolerability profile.
The Journal of Clinical Endocrinology & Metabolism · 2014 · 62 citations · open access
Sitosterolemia Presenting With Severe Hypercholesterolemia and Intertriginous Xanthomas in a Breastfed Infant: Case Report and Brief Review
AbstractCONTEXT: Sitosterolemia is an autosomal recessive disorder characterized by increased intestinal absorption of plant sterols. It is caused by mutations in genes encoding ATP-binding cassette, subfamily G5 (ABCG5) or G8 (ABCG8), and clinical features include elevated plant sterol levels, xanthomas, and accelerated atherosclerosis. Although it was originally reported in patients with normolipemic xanthomas, patients with sitosterolemia also hyperabsorb cholesterol, and serum cholesterol levels tend to be elevated. OBJECTIVE: We report an infant with sitosterolemia who presented with severe hypercholesterolemia and intertriginous xanthomas. CASE REPORT: A 15-month-old Korean girl presented with yellow dermal plaques over flexural areas including the wrist, neck, and gluteal folds, which were consistent with intertriginous xanthomas. The lesions were first noticed at 3 months of age when she was being exclusively breastfed. Her total cholesterol and low-density lipoprotein-cholesterol levels were 675 and 540 mg/dL, respectively. A low-fat/low-cholesterol diet and cholestyramine therapy were introduced. Unexpectedly, her serum cholesterol level decreased dramatically and normalized in 2 months. Cholestyramine was tapered off. The xanthomas also regressed and disappeared by 3 years of age. Gas chromatography-mass spectrometric analysis was performed with serum drawn at 3 years of age when her low-density lipoprotein-cholesterol was 118 mg/dL, which revealed striking elevation of her sitosterol level at 19.36 mg/dL. Direct sequencing for ABCG5 revealed compound heterozygous null mutations c.904+1G>A (p.Met302Asnfs*82) and c.1336C>T(p.Arg446*). CONCLUSIONS: Our case suggests that sitosterolemia can present with severe hypercholesterolemia and intertriginous xanthomas. Sitosterolemia should be suspected when a patient with hypercholesterolemia shows unexpectedly good response to dietary modification or bile acid sequestrant therapy.
Long-Term Follow-Up of a Patient with Sitosterolemia and Hemolytic Anemia with Excellent Response to Ezetimibe
AbstractLong-Term Follow-Up of a Patient with Sitosterolemia and Hemolytic Anemia with Excellent Response to Ezetimibe Sitosterolemia (MIM #210250), also known as phytosterolemia, first described in 1974, is characterized by disruption of the normal homeostatic mechanisms that regulate dietary cholesterol absorption and prevent the accumulation of non-cholesterol sterols. Phytosterols are almost undetectable in plasma from normal individuals. Sitosterolemia is inherited in an autosomal recessive fashion and results from mutations in two genes at the STSL locus that maps to human chromosome 2p21: the ATP-binding cassette,subfamily G, members 5 and 8 (ABCG5 and ABCG8), that encode two proteins known as sterolin-1 and -2.
Clinical Cosmetic and Investigational Dermatology · 2025 · 1 citations · open access
From Xanthomas to Genetic Diagnosis: A Case Report of Sitosterolemia in an Infant with a Homozygous ABCG5 c.1166G>A (p.Arg389His) Variant
AbstractIntroduction: Sitosterolemia is a rare autosomal recessive disorder characterized by disrupted lipid metabolism and elevated plasma plant sterol levels. Clinical manifestations often include cutaneous and tendon xanthomas and hypercholesterolemia; delayed diagnosis can lead to cardiovascular disease and hematological abnormalities. This case report describes an 11-month-old female infant with sitosterolemia who presented with xanthomas appearing around 6 months of age. Genetic sequencing identified a homozygous ABCG5 c.1166G>A (p.Arg389His) mutation. This report aims to discuss the clinical features and genetic diagnosis of sitosterolemia caused by ABCG5 mutations, highlighting the challenges and key characteristics for early diagnosis to improve clinical awareness. Case and Methods: Clinical data of a pediatric patient with sitosterolemia caused by a homozygous ABCG5 gene mutation were retrospectively analyzed. Results: An 11-month-old female infant developed linear xanthomas in the skin folds of her ankles at approximately 6 months of age, which progressively worsened. Blood tests revealed significantly elevated total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels. Sequencing of coding regions for genes associated with familial hypercholesterolemia and sitosterolemia identified a homozygous ABCG5 mutation: c.1166G>A (p.Arg389His). Sanger sequencing confirmed that this variant was inherited from each parent in a heterozygous state. The diagnosis of sitosterolemia was confirmed based on genetic testing ( ABCG5/ABCG8 ), lipid profile results, and clinical presentation. Conclusion: Sitosterolemia should be suspected in patients presenting with cutaneous xanthomas, prompting thorough investigation including lipid profiling, genetic testing, and plasma plant sterol quantification to avoid misdiagnosis as familial hypercholesterolemia (FH). Keywords: sitosterolemia, homozygous, ABCG5 Gene, xanthomas, hypercholesterolemia, low-density lipoprotein cholesterol
Estadística para veterinarios: Análisis de repeticiones por ciclo de parto
AbstractSitosterolemia is an autosomal recessive lipid disorder in which plasma plant sterol levels are extremely elevated and cholesterol levels are often elevated but may be normal. Clinically sitosterolemia is characterized by xanthomas, premature vascular disease, and arthritis. Adolescent boys and girls with sitosterolemia are susceptible to fatal cardiac events. Dermatologists may have a vital role in the diagnosis of this rare but serious condition because early detection and treatment are important in preventing the associated atherosclerotic heart disease. We present a 7-year-old girl with sitosterolemia and tuberous xanthomas.
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.
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