DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for craniosynostosis — screening already-approved drugs against its 44-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCraniosynostosis maps to a 44-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 craniosynostosis 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
fibroblast growth factor 2 (FGF2) — FGF2 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 idydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4OEE · 1.5 Å · ligand 1-O-methyl-2-O-sulfo-alpha-L-idopyranuronic acid (IDY). Experimental structure, not a prediction.
What the evidence adds up to
A 2009 in vitro study on postnatal day-21 wild-type mice (n=18) found that cyclical compressive loading of 0.3 g for 30 minutes daily over 14 days induced premature fusion of the sagittal suture. The nine loaded sutures showed histologic evidence of craniosynostosis and increased alkaline phosphatase activity and bone sialoprotein expression, while the nine unloaded control sutures remained patent. The authors concluded that abnormal mechanical forces may play an epigenetic role in nonsyndromic craniosynostosis, but this has not been tested in humans.
A 2018 retrospective review of 81 patients who underwent primary open cranial vault repair for craniosynostosis at a single US centre from 1995 to 2015 reported no intraoperative deaths, a 1.2% readmission rate for wound infection (one syndromic patient), and a 2.5% reoperation rate for fronto-orbital readvancement (two syndromic patients). Mean hospital stay was 4.31 days. The sample included 14 syndromic patients (17.3%) and 67 nonsyndromic patients; affected sutures were unicoronal (28), metopic (24), sagittal (11), bicoronal (7), multisuture (9), and lambdoid (2). A 2012 review noted that surgical options now include endoscopic suturectomy, spring-mediated cranioplasty, and distraction osteogenesis alongside traditional vault remodelling, but that optimal timing and procedure remain disputed.
A 2017 case report of a 2-year-old Chinese boy with dolichocephaly craniosynostosis identified microduplications on chromosomes 8p11.22 q12.1 and 16q11.2 q21 by array-based DNA hybridisation, with no known pathogenic point mutations in FGFRs or other hotspot genes. A 2018 review stated that craniosynostosis has a prevalence of 1 in 2,500 newborns and that several genes have been identified in its pathogenesis, but that molecular signalling pathways are still being mapped for potential therapeutic targeting.
No drug treatment for craniosynostosis appears in any of these abstracts. What is missing is any clinical trial of a pharmacological intervention, any validated non-surgical therapy, and any patient stratification that might identify which genetic or mechanical subtypes could respond to a repurposed drug. Funding for such trials and for basic research into the mechanical and molecular triggers of suture fusion remains absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Plastic & Reconstructive Surgery · 2009 · 38 citations
Force-Induced Craniosynostosis in the Murine Sagittal Suture
AbstractBACKGROUND: The cause of nonsyndromic craniosynostosis remains elusive. Although compressive forces have been implicated in premature suture fusion, conclusive evidence of force-induced craniosynostosis is lacking. The purpose of this study was to determine whether cyclical loading of the murine calvaria could induce suture fusion. METHODS: Calvarial coupons from postnatal day-21, B6CBA, wild-type mice (n = 18) were harvested and cultured. A custom appliance capable of delivering controlled, cyclical, compressive loads was applied perpendicular to the sagittal suture within the coupon in vitro. Nine coupons were subjected to 0.3 g of force for 30 minutes each day for a total of 14 days. A control group of nine coupons was clamped in the appliance without loading. Analysis of suture phenotype was performed using alkaline phosphatase and hematoxylin and eosin staining techniques and in situ hybridization analysis using bone sialoprotein. RESULTS: Control group sagittal sutures-which normally remain patent in mice-showed their customary histologic appearance. In contradistinction, sagittal sutures subjected to cyclic loading showed histologic evidence of premature fusion (craniosynostosis). In addition, alkaline phosphatase activity and bone sialoprotein expression were observed to be increased in the experimental group when compared with matched controls. CONCLUSIONS: An in vitro model of force-induced craniosynostosis has been devised. Premature fusion of the murine sagittal suture was induced with the application of controlled, cyclical, compressive loads. These results implicate abnormal forces in the development of nonsyndromic craniosynostosis, which supports our global hypothesis that epigenetic phenomena play a crucial role in the pathogenesis of craniosynostosis.
Twenty-Year Outcome Experience With Open Craniosynostosis Repairs
AbstractBACKGROUND: Surgical intervention during infancy for both syndromic and nonsyndromic patients with craniosynostosis remains the criterion standard of treatment with the 2 main options being open vault remodeling versus minimally invasive surgery. Although open cranial vault remodeling was initially considered a high-risk procedure, many advances have improved its safety. Despite this, there is a paucity of literature on the long-term outcomes of contemporary open craniosynostosis repair. METHODS: A retrospective review of all patients who underwent primary open cranial vault repair for craniosynostosis by a single surgeon (J.A.A.) at New York-Presbyterian Hospital from 1995 to 2015 was performed. RESULTS: For primary open repair, 81 patients (46 males, 35 females) were analyzed, and affected sutures included unicoronal (28), bicoronal (7), metopic (24), sagittal (11), lambdoid (2), and multisuture (9). Fourteen patients (17.3%) were syndromic. Mean (SD) operative patient age was 13.81 (16.24) months: 34 (42%) were 0 to 6 months; 26 (32%), 7 to 12 months; and 21 (26%), 12 months of age or older. There were no intraoperative complications. Mean (SD) estimated blood loss for the plastic surgery portion of all cases was 74.53 (72.34) mL, and total estimated blood loss was 174.93 (182.23) mL. Mean (SD) hospital length of stay was 4.31 (1.59) days. One syndromic patient was readmitted for a wound infection (1.2%) that was successfully treated with antibiotics, and 2 syndromic patients (2.5%) had reoperation for fronto-orbital readvancement. CONCLUSIONS: This 20-year experience demonstrates the safety of modern open craniosynostosis repairs at a large academic medical center with low rates of mortality (0%), complications (1.2%), and reoperations (2.5%).
Current Opinion in Otolaryngology & Head & Neck Surgery · 2012 · 19 citations
Current approaches to management of nonsyndromic craniosynostosis
AbstractPURPOSE OF REVIEW: Surgical alternatives to traditional cranial vault remodeling for the treatment of craniosynostosis are being discussed in recent plastic and neurosurgical literature. This review highlights recent developments and discusses the risks as well as benefits of each. RECENT FINDINGS: Surgical treatment of craniosynostosis has evolved from simple suturectomy, to extensive cranial vault remodeling, and now back to the minimally invasive. Options today include endoscopic suturectomies, spring-mediated cranioplasties, and distraction osteogenesis as well as cranial vault remodeling. There are disagreements among centers on the most optimal timing and best operative procedure. SUMMARY: Clinicians should be aware that different surgical treatments are rapidly being developed for nonsyndromic craniosynostosis.
Journal of Korean Neurosurgical Society · 2016 · 6 citations · open access
Current and Future Perspectives in Craniosynostosis
AbstractCraniosynostosis has a varied clinical spectrum, ranging from isolated single suture involvement to multi-sutural fusions. Greater understanding of the pathogenesis of craniosynostosis has led to the development of practical treatment protocols. Three stages of growth have determined the approach to managing craniosynostosis : the early period, up to 12 months; the intermediate period, from 1 to 10 years; and the late period, beginning at 10 years. This review discusses current surgical management and future perspectives in craniosynostosis.
Novel chromosomal microduplications associated with dolichocephaly craniosynostosis
AbstractINSTRUCTION: Craniosynostosis is a human disorder characterized by the premature fusing of the cranial sutures in infants. Point mutations in hotspot genes such as FGFRs are the well-recognized causes of syndromic craniosynostosis, but chromosomal abbreviations may also play an important role in developing this disease. Here, we report the case in China of a 2-year-boy dolichocephaly craniosynostosis. Karyotyping by both G-bind staining and array-based DNA hybridization identified microduplications on Chromosomes 8p11.22 q12.1 and 16q11.2 q21, but none of the known pathogenic mutations was detected. CONCLUSIONS: This finding not only expands knowledge on the genetic mechanism of craniosynostosis but also provides a new target for the early diagnosis of this rare disease.
IOP Conference Series Earth and Environmental Science · 2018 · 0 citations · open access
Molecular genetics of craniosynostosis
AbstractTight regulation process and complex interplay occur along the osteogenic interfaces of the cranial sutures in normal growth and development of the skull. Cranial sutures serve as sites of bone growth while maintaining a state of patency to accommodate the developing brain. Cranial sutures are fibro-cellular structures that separate the rigid plates of the skull bones. Premature fusion of one or more cranial sutures leads to a condition known as craniosynostosis. Craniosynostosis is one of the most common craniofacial anomalies with a prevalence of 1 in 2,500 newborns. Several genes have been identified in the pathogenesis of craniosynostosis. Molecular signaling events and the intracellular signal transduction pathways implicated in the suture pathobiology will provide a useful approach for therapeutic targeting.
World Neurosurgery · 2025 · 0 citations · open access
Craniosynostosis in Africa: Insights from 8 Countries—A Systematic Review and Meta-Analysis
AbstractOBJECTIVE: Craniosynostosis is a congenital skull deformity that impacts development and quality of life of children if left untreated. This study aimed to evaluate literature regarding presentation, treatment, and outcomes of craniosynostosis in Africa. METHODS: A systematic review of the literature using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Fourteen retrospective/prospective studies with 620 patients and 14 case reports involving 27 cases (8 countries) were included. In 12 articles, 56.6% of patients (317/560) were males, with a mean age of 2.4 years (confidence interval [CI]: 1.1-3.7). Abnormal head shape was the most reported presentation in 77.8% of cases (332/427, 8 articles). Syndromic craniosynostosis was seen in 25.2% (CI: 13.7%-36.6%). Common phenotypes were trigonocephaly in 31.5% (CI: 3.6%-59.4%), anterior plagiocephaly in 23.2% (CI: 5.1%-41.3%), and scaphocephaly in 22.1% (CI: 13.5%-30.8%). Five hundred seventy eight patients, 99.5% (CI: 99.0%-100.0%), underwent surgical treatment. Vault remodeling was performed in 72.9% patients (CI: 47.4%-98.6%). Postoperative complications included cerebrospinal fluid leaks 5.4% (CI: 0.0%-11.6%) and surgical site infections 4.5% (CI: 0.0%-10.8%). Follow-up ranged between 0.2 and 40.9 months; 95.6% of cases (CI: 90.1%-100.0%) exhibited improved deformity and neurological deficits at last follow-up. The mortality rate was 3.1% (CI: 0.0%-6.9%, 2 articles). CONCLUSIONS: Few studies on craniosynostosis in Africa highlight the need for more research. Treatment with open techniques yields few complications and a low mortality rate. Early diagnosis and collaborative data reporting will enhance understanding of its burden and variations across Africa.
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.
