DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Cole-Carpenter syndrome — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCole-Carpenter syndrome maps to a 3-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 cole-carpenter syndrome 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
prolyl 4-hydroxylase subunit beta (P4HB) — P4HB 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 pgedrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6I7S · 2.5 Å · ligand TRIETHYLENE GLYCOL (PGE). Experimental structure, not a prediction.
What the evidence adds up to
The 2015 abstract describes a single 12-year-old female patient with a Cole-Carpenter syndrome phenotype who was enrolled in a study of atypical osteogenesis imperfecta. Genomic sequencing found she had a homozygous c.118G>T mutation predicted to result in a p.Glu40* amino acid change in exon 1 of CRTAP. The authors suggest this patient and others with Cole-Carpenter syndrome may have a rare form of OI type 3. The literature has described only a few patients with Cole-Carpenter syndrome involving multiple fractures and bone deformities similar to severe OI, along with proptosis, blue sclerae, hydrocephalus, and distinct facial features but normal intelligence.
The 2011 abstract concerns Carpenter syndrome, a different disorder caused by mutations in RAB23, and provides no data on Cole-Carpenter syndrome. The 2017 abstract reports a trial of bendamustine plus rituximab for chronic cold agglutinin disease, with 32 of 45 patients (71%) responding, 18 (40%) achieving complete response and 14 (31%) partial response. Among 14 patients previously treated with rituximab or fludarabine-rituximab, 7 (50%) responded. Hemoglobin increased by a median of 4.4 g/dL in complete responders, 3.9 g/dL in partial responders, and 3.7 g/dL in the whole cohort. Grade 3-4 neutropenia occurred in 15 patients (33%), and 13 (29%) had their dose reduced. This abstract has no relevance to Cole-Carpenter syndrome.
No drug treatment for Cole-Carpenter syndrome is reported in any of these abstracts. The only molecular finding is a single patient with a homozygous CRTAP mutation, but this has not been confirmed in other patients. What is still missing is a larger case series to establish whether CRTAP mutations are consistently found in Cole-Carpenter syndrome, funding for molecular analysis of additional patients, and any clinical trial design for a potential treatment.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Blood · 2017 · 141 citations · open access
Bendamustine plus rituximab for chronic cold agglutinin disease: results of a Nordic prospective multicenter trial
Abstractdays 1 and 2 for 4 cycles at a 28-day interval. Thirty-two patients (71%) responded; 18 (40%) achieved complete response (CR) and 14 (31%) partial response (PR). Among 14 patients previously treated with rituximab or fludarabine-rituximab, 7 (50%) responded to bendamustine-rituximab (3 CR and 4 PR). Hemoglobin levels increased by a median of 4.4 g/dL in the complete responders, 3.9 g/dL in those achieving PR, and 3.7 g/dL in the whole cohort. The 10th percentile of response duration was not reached after 32 months. Grade 3-4 neutropenia occurred in 15 patients (33%), but only 5 (11%) experienced infection with or without neutropenia. Thirteen patients (29%) had their dose of bendamustine reduced. In conclusion, bendamustine-rituximab combination therapy is highly efficient, sufficiently safe, and may be considered in first line for patients with CAD requiring therapy. The trial was registered at www.clinicaltrials.gov as #NCT02689986.
Human Mutation · 2011 · 44 citations · open access
Carpenter syndrome: extended <i>RAB23</i> mutation spectrum and analysis of nonsense‐mediated mRNA decay
AbstractCarpenter syndrome, a rare autosomal recessive disorder characterized by a combination of craniosynostosis, polysyndactyly, obesity, and other congenital malformations, is caused by mutations in RAB23, encoding a member of the Rab-family of small GTPases. In 15 out of 16 families previously reported, the disease was caused by homozygosity for truncating mutations, and currently only a single missense mutation has been identified in a compound heterozygote. Here, we describe a further 8 independent families comprising 10 affected individuals with Carpenter syndrome, who were positive for mutations in RAB23. We report the first homozygous missense mutation and in-frame deletion, highlighting key residues for RAB23 function, as well as the first splice-site mutation. Multi-suture craniosynostosis and polysyndactyly have been present in all patients described to date, and abnormal external genitalia have been universal in boys. High birth weight was not evident in the current group of patients, but further evidence for laterality defects is reported. No genotype-phenotype correlations are apparent. We provide experimental evidence that transcripts encoding truncating mutations are subject to nonsense-mediated decay, and that this plays an important role in the pathogenesis of many RAB23 mutations. These observations refine the phenotypic spectrum of Carpenter syndrome and offer new insights into molecular pathogenesis.
American Journal of Medical Genetics Part A · 2015 · 0 citations
In this issue
Abstractattempt to explain the molecular basis of Cole-Carpenter syndrome.The literature has described only a few patients with Cole-Carpenter syndrome involving multiple fractures and bone deformities similar to severe osteogenesis imperfecta (OI).These patients have also suffered from proptosis, blue sclerae, hydrocephalus, and distinct facial features but had normal intelligence.Because little is known about the syndrome's molecular basis and inheritance pattern, the researchers describe a 12-year-old female patient with a Cole-Carpenter syndrome phenotype who was enrolled in a study of atypical OI.Genomic sequencing found that she had a homozygous c.118G>T mutation predicted to result in a p.Glu40* amino acid change in exon 1 in CRTAP.Balasubramanian et al. suggest that the girl and other patients with Cole-Carpenter syndrome may have a rare form of OI type 3. Researchers call for molecular analysis of patients with Cole-Carpenter syndrome to confirm this observation.
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.
