DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cerebrotendinous xanthomatosis — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCerebrotendinous xanthomatosis maps to a 2-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
approvedChenodeoxycholic acidApproved drug
Structures already discussed alongside cerebrotendinous xanthomatosis in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Bile Salt Hydrolase A from Lactobacillus gasseri — Chenodeoxycholic acid has a real, experimentally solved structure in complex with this target (PDB 7SVG, 1.35 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 jn3drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7SVG · 1.35 Å · ligand Chenodeoxycholic acid (JN3). Experimental structure, not a prediction.
What the evidence adds up to
In 1937 Van Bogaert and colleagues described a patient with cerebrotendinous xanthomatosis who died at age 40; a postmortem study followed. Two further patients were reported within three years. A 2007 case described a 43-year-old woman with progressive dementia since childhood, gait ataxia, mild polyneuropathy, painful Achilles tendon xanthomas, and bilateral cataract surgery in adolescence. Blood tests showed elevated cholestanol with normal cholesterol. Cerebral CT showed slight atrophy, mainly of the cerebellum. After treatment with simvastatin 20 mg/day and chenodeoxycholic acid 15 mg/kg/day, further disease progression was prevented. The authors noted that up to 30% of patients do not have severe xanthomas, making early diagnosis difficult, and that treatment should start as early as possible to prevent irreversible nervous system damage.
A 2023 study reported a patient with a milder phenotype. DNA sequencing of the CYP27A1 gene found a pathogenic variant (p.Arg474Trp) and a variant of unknown significance (p.Met130Ile) that caused a slight modification of the protein’s functional structure. The authors concluded that this variant in homozygosis or compound heterozygosis with other biallelic pathological mutations may explain the observed clinical phenotype. They noted that clinical manifestations are heterogeneous and sometimes wrongly suggest other diseases, and that some patients present an “incomplete” phenotype that could be redefined as a variant with further study.
No controlled trial data are available. The evidence rests on case reports and a single case series. It remains unknown whether the combination of simvastatin and chenodeoxycholic acid works in all patients, what the optimal doses are, or how long treatment must continue. No randomised trial has been conducted, no patient stratification by genotype or phenotype has been tested prospectively, and no funding for such a trial is described in these reports.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cambridge University Press eBooks · 2004 · 3 citations
Cerebrotendinous xanthomatosis
AbstractIn 1937, Van Bogaert et al., (1937a) described a patient with cerebrotendinous xanthomatosis (CTX) and made a detailed follow-up of this man. After the patient died at the age of 40 years, a thorough postmortem study was performed. This clinicopathologic description is the most detailed ever reported for CTX. Within 3 years, two additional patients were described (Van Bogaert et al., 1937b; Epstein, 1940).
DMW - Deutsche Medizinische Wochenschrift · 2007 · 2 citations
Zerebrotendinöse Xanthomatose
AbstractHISTORY AND CLINICAL FINDINGS: A 43-year-old woman had since childhood suffered from progressive dementia. Gait ataxia and mild polyneuropathy were noted in the neurological examination. She also had painful xanthomas of the achilles tendons. A bilateral cataract operation had been performed during adolescence. INVESTIGATIONS: An elevated concentration of cholestanol and a normal cholesterol level were found in the blood samples. The cerebral computed tomography revealed slight cerebral atrophy, predominantly affecting the cerebellum. Neurophysiological tests detected a sensory polyneuropathy in the legs. In addition the electroencephalogram showed a generalized slowing of electrical activity. DIAGNOSIS, TREATMENT AND COURSE: Clinical findings and laboratory values indicated the diagnosis of a cerebrotendinous xanthomatosis. After initiation of a drug therapy, based on a combination of an HMG-CoA-reductase inhibitor (simvastatin 20 mg/day) and a bile acid, chenodeoxycholic acid (15 mg/kg/day), further progression of the disease was prevented. CONCLUSION: The diagnosis of cerebrotendinous xanthomatosis is easily made in patients presenting all clinical symptoms expected in the disease. However, up to 30% of the patients do not show severe xanthomas. Especially in early stages of the disease the diagnosis may be difficult. Treatment can be efficacious and should be started as early as possible to prevent irreversible damage, particularly in the nervous system.
International Journal of Neuroscience · 2023 · 1 citations
Case Report: a novel CYP27A1 gene variant in a patient with cerebrotendinous xanthomatosis with unusual clinical findings
AbstractPURPOSE/AIM OF THE STUDY: Cerebrotendinous xanthomatosis is a disease with important clinical and molecular heterogeneity. CYP27A1 gene was described as the cause of these defects, with more than 50 mutations involved in the disease. The objective of this study was to carry out a genetic study and a clinical description of a patient with unusual clinical manifestation of the disease. MATERIALS AND METHODS: DNA sequencing was used for the evaluation of CYP27A1 exon sequences and their intron/exon boundaries. Copy number variants were calculated using a method based on depth of sequencing coverage. In addition, the potential effects of the missense variants were analyzed, and an in-silico protein modeling tool was used. Finally, a patient case description was performed in order to evaluate patient phenotype according to genetic results. RESULTS: Patient clinical features indicate the possible presence of a disease milder phenotype. When analyzing the CYP27A1 gene, patient presents a pathogenic variant (p.Arg474Trp) and a variant of unknown significance (p.Met130Ile) that causes a slight modification of the protein functional structure. This variant in homozygosis or double or compound heterozygosis together with other biallelic pathological mutations may be the cause of the clinical phenotype observed in the reported patient. CONCLUSIONS: Clinical manifestations of cerebrotendinous xanthomatosis are heterogeneous, and sometimes wrongly suggest the presence of other diseases. Some patients seem to present an "incomplete" phenotype, which could be redefined as a variant of the disease with further studies. The evaluation of new mutations allows for earlier diagnosis and greater effectiveness in its treatment.
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.
