DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for clubfoot — screening already-approved drugs against its 13-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleClubfoot maps to a 13-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 clubfoot 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
polycystin 1, transient receptor potential channel interacting (PKD1) — PKD1 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 1rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8ZKH · 2.3 Å · ligand (1R)-2-{[(S)-{[(2S)-2,3-dihydroxypropyl]oxy}(hydroxy)phosphoryl]oxy}-1-[(hexadecanoyloxy)methyl]ethyl
(9Z)-octadec-9-enoate (PGW). Experimental structure, not a prediction.
What the evidence adds up to
Between 1996 and 2006 in the United States, the estimated number of infants under six months diagnosed with clubfoot stayed fairly constant at about 2140 per year, while surgical releases in patients under twelve months fell from 1641 to 230. The percentage of clubfeet treated with extensive surgery dropped from just over 70% in 1996 to just over 10% in 2006, a decline of 6.7% per year. The authors attribute this to increased use of less invasive techniques such as the Ponseti method.
A 2009 study of 91 patients (133 feet) treated with the Ponseti method between 2005 and 2007 reported good results in 70% of feet, indeterminate in 7.5%, fair in 6.76%, and poor in 15.8%. Good results improved each year, from 50% in 2005 to 72.2% in 2006 and 93% in 2007. Poor results were linked to very rigid feet (6%), problems with Denis-Brown splint availability (14.5%), ill-fitting shoes (15%), faulty correction technique, and poor family compliance with bracing (11.2%). A delayed start of treatment had no significant effect on outcomes.
A 1996 paper notes that conservative treatment in experienced hands leads to a satisfactory result in about one third of cases, and recommends primary conservative treatment with surgery at age 2–5 months for resistant cases. The same text calls for more prospective studies and generally accepted grading systems. A 2010 paper confirms that the rate of extensive surgery in the US declined substantially over the decade studied.
What is still missing: prospective studies with standardised outcome measures, consistent long-term follow-up beyond four years to track recurrence, and reliable methods to ensure family compliance with bracing protocols. No drug is mentioned in any of these abstracts.
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 Bone and Joint Surgery · 2010 · 119 citations
Has the Rate of Extensive Surgery to Treat Idiopathic Clubfoot Declined in the United States?
AbstractBACKGROUND: In the late 1990s, renewed interest emerged in less invasive treatment options, most notably the Ponseti method, to correct idiopathic clubfoot deformity. Recently, reports from several centers have demonstrated that such minimally invasive techniques may be used reliably to correct this complex deformity. The present study sought to determine whether the rate of extensive surgical releases to treat idiopathic clubfoot in the United States has decreased. METHODS: We used data from the Centers for Disease Control and Prevention and the Nationwide Inpatient Sample to determine the number of live births, the number of patients diagnosed with clubfoot, and the number of extensive surgical releases that were performed each year from 1996 to 2006. The trends over time were evaluated with use of regression analysis, and changes in frequency were analyzed with use of time series analysis. The percentage of clubfeet that were treated with surgery in each year was calculated by dividing the number of surgical release procedures by the number of clubfoot diagnoses. RESULTS: Between 1996 and 2006, the estimated number of patients under six months of age diagnosed with clubfoot remained fairly constant, averaging 2140 infants per year. The linear equation estimated a slight decrease of approximately thirty-one infants with clubfoot per year (R(2) = 0.51, p < 0.05). In contrast, in the same decade, the estimated number of surgical releases performed in patients less than twelve months of age decreased substantially, from 1641 releases in 1996 to 230 releases in 2006. The linear equation estimated a decrease of approximately 157 surgical releases per year (R(2) = 0.83, p < 0.05). The trend analysis indicated that the percentage of clubfeet treated with surgical release generally decreased over time at a rate of 6.7% per year, decreasing from just over 70% in 1996 to just over 10% in 2006 (R(2) = 0.81, p < 0.05). CONCLUSIONS: In the United States between 1996 and 2006, the rate of extensive surgery to treat idiopathic clubfoot in patients less than twelve months old decreased substantially. This trend is likely due to an increased use of less invasive techniques, such as the Ponseti method, which a growing body of evidence has shown to be a viable treatment option for clubfoot.
Journal of Bone and Joint Surgery · 2004 · 58 citations
Dynamic Foot-Pressure Measurement in the Assessment of Operatively Treated Clubfeet
AbstractBACKGROUND: Decreased motion of the subtalar joint is common after operative treatment of idiopathic clubfeet. The purposes of this study were to validate parameters of dynamic foot-pressure measurement that enable detection of physiological pronation of the subtalar joint and to analyze the consequences of absent or decreased pronation following clubfoot surgery on long-term functional results. METHODS: To validate parameters of dynamic foot-pressure measurement, we initially analyzed two control groups: one of forty asymptomatic normal feet and the other of five feet with a previous subtalar joint arthrodesis. The resulting parameters were then applied to a group of nineteen patients with twenty-four idiopathic clubfeet for whom initial conservative treatment had failed and in whom a posterior surgical release (lengthening of the Achilles tendon and release of the posterior ankle capsule) had been performed at a mean age of twenty months. The mean duration of follow-up was forty-one years. All feet were evaluated radiographically, and the clinical results were assessed with the American Orthopaedic Foot and Ankle Society score. RESULTS: An interruption in the rise of the pressure-time curve and a short medial deviation of the center of pressure path immediately after heel strike are reliable and objective characteristics of pronation movement of the subtalar joint. Nineteen clubfeet had a demonstrable pronation movement, and five clubfeet did not. The nineteen feet with pronation movement were either asymptomatic (twelve feet) or mildly painful on occasion (seven feet). The mean American Orthopaedic Foot and Ankle Society score for the nineteen feet was 87 points. The five feet without pronation movement were moderately painful during strenuous activities only (four feet) or were nearly always painful (one foot). The mean score for those feet was 57 points. There was a significant difference between these two groups with regard to the pain scores and the total scores (p < 0.001), but there was no appreciable difference regarding function and hindfoot motion. It was not possible to distinguish between these two groups on the basis of the findings of the physical or radiographic examinations. CONCLUSIONS: Idiopathic clubfeet with preserved hindfoot pronation have a better long-term prognosis. Preservation of functional mobility of the subtalar joint is a key factor in the treatment of clubfoot deformity.
Journal of Pediatric Orthopaedics B · 1996 · 11 citations
Critical Aspects of Neonatal Surgery in Clubfoot
AbstractGood results after early operative treatment of clubfoot has been reported by some investigators. Most have recommended early conservative treatment and later surgical procedures in resistant cases. Operation immediately after birth is demanding, and the operative team must master all problems of neonatal surgery, anesthesiology, and postoperative care. Conservative treatment in experienced hands may lead to a satisfactory result in one third of cases. We recommend primarily conservative treatment, but patients with resistant cases must undergo operation at age 2-5 months. We need more prospective studies and generally accepted grading systems of results.
Acta chirurgiae orthopaedicae et traumatologiae Cechoslovaca · 2009 · 9 citations · open access
The Ponseti Method of Treatment of Congenital Clubfoot - First Experiences
AbstractPURPOSE OF THE STUDY: To provide a detailed description of the Ponseti method and report the first results of its use, including factors that played a role. MATERIAL AND METHODS: In the 2005-2007 period, 91 patients with idiopathic rigid clubfoot (133 feet) were treated by the Ponseti method. The group comprised 62 boys and 29 girls. In most patients the Ponseti method was used as primary treatment, or by 3 months of age when previous treatment failed. In five children this treatment was started between the 3rd and 8th months of age. The result were evaluated by the criteria described by Richards et al., who distinguished four groups. The result was regarded as good when a permanent plantigrade foot was achieved (group 1). Plantigrade feet likely to require posterior release later were considered indeterminate rusults (group 2). Feet that needed posterior release, anterior tibial muscle transfer or lateral column shortening fell in the fair result group (3). Feet requiring complete subtalar release were classified as poor results (group 4). The results achieved in each year were statistically evaluated using Fisher's test (p<0.05). RESULTS: The overall evaluation for 3 years showed good results in 70%, indeterminate in 7.5%, fair in 6.76% and poor in 15.8% of the treated feet. A detailed analysis for each year revealed that, in 2005, good results (50%) were recorded in a significantly lower number of feet than in 2006 (72.2%; p=0.032) and 2007 (93%; p<0.001). On comparison of the years 2006 and 2007, good results in 2007 were found in a significantly higher number of feet than in 2006 (p=0.019). The poor results were due to 1) very rigid feet (6%); 2) initial problems with availability of Denis-Brown splints (19 feet; 14.5%); 3) problems with shoes not made to custom and not fitting patient's little feet (20 feet; 15%) 4) faulty techniques of correcting the deformity (4 feet); 5) poor family cooperation in compliance with the bracing protocol (15 feet; 11.2%). Some of the factors were combined. A delayed beginning of the treatment had no significant effect on the results. DISCUSSION: Our 3-year results of clubfoot treatment, by which plantigrade foot position was acheved on average in 77.5% of the patients, are in agreement with those achieved outside Ponseti centres. However, there were clear differences, with the worst results in 2005. The results comparable with those of Ponseti and his co-workers were achieved by us only in 2007. In accordance with the findings of Richards et al. we suggest that the percentage of short-term good results can change insignificantly within 4 years because of increased recurrence of deformities. CONCLUSIONS: Although our initial results were worse than reported in the literature, it can be concluded that the Ponseti method of treating idiopathic clubfoot is more efficient that the methods used previously and can be recommended as an efficient, safe and economical technique. Good compliance with the protocol improves the therapeutic results.
Cisco CallManager Fundamentals: A Cisco AVVID Solution (2nd Edition)
AbstractGood results after early operative treatment of clubfoot has been reported by some investigators. Most have recommended early conservative treatment and later surgical procedures in resistant cases. Operation immediately after birth is demanding, and the operative team must master all problems of neonatal surgery, anesthesiology, and postoperative care. Conservative treatment in experienced hands may lead to a satisfactory result in one third of cases. We recommend primarily conservative treatment, but patients with resistant cases must undergo operation at age 2-5 months. We need more prospective studies and generally accepted grading systems of results.
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.
