DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Holt-Oram syndrome — 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 moduleHolt-Oram syndrome 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 holt-oram 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
T-box transcription factor 5 (TBX5) — TBX5 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 2-{2-[2-(2-ethoxy-ethoxydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2X6U · 1.9 Å · ligand 2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL (PE4). Experimental structure, not a prediction.
What the evidence adds up to
The 1994 genetic-linkage study of two large families mapped the Holt-Oram syndrome gene to the long arm of chromosome 12 (12q2), with a combined multipoint lod score of 16.8, indicating odds greater than 10¹⁶:1 that the defect lies there. In Family A, all 19 affected members had mild-to-moderate skeletal deformities (triphalangeal thumbs, carpal-bone dysmorphism) and moderate-to-severe congenital cardiac defects (ventricular or atrial septal defects, atrioventricular-canal defects). In Family B, 18 affected members had moderate-to-severe skeletal deformities including phocomelia, but 12 of them had no cardiac defects and six had only atrial septal defects. The same locus on 12q2 produced this wide range of phenotypes, showing the gene is important for both skeletal and cardiac development.
Two case reports from 2019 describe clinical and radiological features of Holt-Oram syndrome in two patients, but provide no quantitative outcomes or treatment data. A 2017 case report describes a 31-year-old man with Holt-Oram syndrome who underwent wide excision of a tongue lesion with radical neck dissection; the report focuses on anaesthetic challenges and a safe outcome, but gives no survival or response data.
A 2024 cross-sectional study of 569 older adults examined the association between oral health-related quality of life and temporomandibular disorder symptoms, but this study did not involve Holt-Oram syndrome patients. It found that 33.4% had mild and 9.5% had moderate/severe TMD symptoms, and those with any TMD symptom had a 38% higher prevalence ratio for worst OHRQoL (95%CI 1.04-1.82) compared to those without.
No drug treatment, clinical trial, or therapeutic intervention for Holt-Oram syndrome appears in these abstracts. What is missing is any trial design, patient stratification, or funding for a drug-repurposing study in this rare genetic condition.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 1994 · 393 citations · open access
The Clinical and Genetic Spectrum of the Holt-Oram Syndrome (Heart-Hand Syndrome)
AbstractBACKGROUND: The Holt-Oram syndrome is an autosomal dominant condition characterized by skeletal abnormalities that are frequently accompanied by congenital cardiac defects. The cause of these disparate clinical features is unknown. To identify the chromosomal location of the Holt-Oram syndrome gene, we performed clinical and genetic studies. METHODS: Two large families with the Holt-Oram syndrome were evaluated by radiography of the hands, electrocardiography, and transthoracic echocardiography. Genetic-linkage analyses were performed with polymorphic DNA loci dispersed throughout the genome to identify a locus that was inherited with the Holt-Oram syndrome in family members. RESULTS: A total of 19 members of Family A had Holt-Oram syndrome with mild-to-moderate skeletal deformities, including triphalangeal thumbs and carpal-bone dysmorphism. All affected members of Family A had moderate-to-severe congenital cardiac abnormalities, such as ventricular or atrial septal defects or atrioventricular-canal defects. Eighteen members of a second kindred (Family B) had Holt-Oram syndrome with moderate-to-severe skeletal deformities, including phocomelia. Twelve of the affected members had no cardiac defects; six had only atrial septal defects. Genetic analyses demonstrated linkage of the disease in each family to polymorphic loci on the long arm of chromosome 12 (combined multipoint lod score, 16.8). These data suggest odds greater than 10(16):1 that the genetic defect for Holt-Oram syndrome is present on the long arm of chromosome 12 (12q2). CONCLUSIONS: Mutations in a gene on chromosome 12q2 can produce a wide range of disease phenotypes characteristic of the Holt-Oram syndrome. This gene has an important role in both skeletal and cardiac development.
Annals of Cardiac Anaesthesia · 2017 · 5 citations · open access
Holt–Oram Syndrome: Anesthetic Challenges and Safe Outcome
AbstractHolt-Oram syndrome (HOS) is an autosomal dominant disease with skeletal and cardiac manifestations. We here are presenting a 31-year-old man and a diagnosed case of HOS, with an ulceroproliferative lesion on lateral border of the tongue, was posted for wide excision of lesion with primary closure and left side radical neck dissection.
Association between oral health-related quality of life and symptoms of temporomandibular disorder among older adults: A cross-sectional study
AbstractOBJECTIVE: Evaluate the association between oral health-related quality of life (OHRQoL) and self-reported symptoms of TMD. METHODS: = 569). Both TMD symptoms and OHRQoL were assessed by Fonseca Anamnestic Index (FAI) and Oral Health Impact Profile-14 (OHIP-14), respectively. Prevalence (those answering "frequently" or "always" in at least one question), severity (total means scores), and extent (number of questions answered as "frequently" or "always") of OHRQoL were estimated. RESULTS: Overall, 33.4% and 9.5% had mild or moderate/severe TMD symptoms. Those with any symptom of TMD had a prevalence ratio (PR) 38% higher for the worst OHRQoL (95% confidence interval [95%CI]:1.04-1.82) compared to those without TMD symptoms. Worst OHRQoL were observed for those with mild (PR:1.35; 95%CI:1.01-1.81) and moderate/severe TMD (PR:1.53; 95%CI:1.04-2.26). Similar results were detected in the severity and extent of OHRQoL. CONCLUSION: Severity TMD was associated with worse ORHQoL.
CHRISMED Journal of Health and Research · 2019 · 2 citations · open access
Holt–Oram syndrome – Case series of two reports
AbstractHolt–Oram syndrome is a rare genetic autosomal dominant disorder which affects the upper limbs and heart. It is also known as “heart–hand” syndrome or “atriodigital dysplasia.” The present article describes the clinical and radiological images of the features of Holt–Oram syndrome in two patients.
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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