DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for orofacial cleft 15 — 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 moduleOrofacial cleft 15 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 orofacial cleft 15 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.
What the evidence adds up to
A 2012 systematic review of cleft lip and palate treatment found only 28 randomised controlled trials among 170 articles identified. The experimental approaches tested in those trials included infant orthopaedics, rectal acetaminophen, palatal block with bupivacaine, infraorbital nerve block with bupivacaine, osteogenesis distraction, intravenous dexamethasone sodium phosphate, and alveoloplasty with bone morphogenetic protein-2. The review concluded that few randomised trials address cleft treatment, especially surgical repair, and called for more multicentre collaboration to reduce variation in treatment and to provide evidence-based practice. No survival or response-rate numbers were reported.
A 2015 review of Hedgehog signalling in upper lip formation states that orofacial clefting is one of the most common outcomes of retarded facial growth or fusion, and that Shh signalling is indispensable for normal embryonic development. Disruption of Shh signalling can result in craniofacial disorders including cleft lip. The review notes that a detailed mechanism linking individual signalling pathways to cleft lip remains elusive. No clinical trial data or patient numbers are given.
A 2014 review of orofacial cleft aetiology reports that these anomalies affect approximately 1 in 1000 people. The aetiology is complex, involving genetic and environmental factors. Non-syndromic clefts are more common and are thought to arise from gene–environment interactions. The review describes genes identified in humans and animal models but provides no treatment outcomes, survival data, or response rates.
What is still missing are large, multicentre randomised controlled trials that test surgical and non-surgical interventions with sufficient statistical power, as well as studies that stratify patients by genetic or environmental risk factors. Funding for such trials and for basic research into the signalling pathways that remain poorly understood is lacking.
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 Surgery International · 2012 · 96 citations · open access
Protocols in Cleft Lip and Palate Treatment: Systematic Review
AbstractObjectives. To find clinical decisions on cleft treatment based on randomized controlled trials (RCTs). Method. Searches were made in PubMed, Embase, and Cochrane Library on cleft lip and/or palate. From the 170 articles found in the searches, 28 were considered adequate to guide clinical practice. Results. A scarce number of RCTs were found approaching cleft treatment. The experimental clinical approaches analyzed in the 28 articles were infant orthopedics, rectal acetaminophen, palatal block with bupivacaine, infraorbital nerve block with bupivacaine, osteogenesis distraction, intravenous dexamethasone sodium phosphate, and alveoloplasty with bone morphogenetic protein-2 (BMP-2). Conclusions. Few randomized controlled trials were found approaching cleft treatment, and fewer related to surgical repair of this deformity. So there is a need for more multicenter collaborations, mainly on surgical area, to reduce the variety of treatment modalities and to ensure that the cleft patient receives an evidence-based clinical practice.
BioMed Research International · 2015 · 37 citations · open access
The Roles of Hedgehog Signaling in Upper Lip Formation
AbstractCraniofacial development consists of a highly complex sequence of the orchestrated growth and fusion of facial processes. It is also known that craniofacial abnormalities can be detected in 1/3 of all patients with congenital diseases. Within the various craniofacial abnormalities, orofacial clefting is one of the most common phenotypic outcomes associated with retarded facial growth or fusion. Cleft lip is one of the representative and frequently encountered conditions in the spectrum of orofacial clefting. Despite various mechanisms or signaling pathways that have been proposed to be the cause of cleft lip, a detailed mechanism that bridges individual signaling pathways to the cleft lip is still elusive. Shh signaling is indispensable for normal embryonic development, and disruption can result in a wide spectrum of craniofacial disorders, including cleft lip. This review focuses on the current knowledge about the mechanisms of facial development and the etiology of cleft lip that are related to Shh signaling.
Dicle Medical Journal / Dicle Tip Dergisi · 2014 · 5 citations · open access
Congenital orofacial clefts: Etiology and Frequency
AbstractOrofacial clefts are congenital structural anomalies of the lip and/or palate. These anomalies affect ~1/1000 in the community. The etiology of orofacial clefts is complex, including various genetic and environmental agents. Syndrome is not accompanied by any isolated orofacial clefts are more common, although environmental factors often play a role in the etiology. Mendelian or teratogenic origins; the non-syndromic forms of orofacial clefts are more common and are likely due to secondary gene–environment interactions. Latest researches in both molecular and quantitative approaches have begun to identify the genes responsible for the rare syndromic forms of cleft and have also identified both candidate genes and loci for the more common and complex non-syndromic variants. Animal models, have also contributed greatly to an comprehension of these anomalies. We aimed to describes genes that are involved in orofacial clefts in humans and animal models and explores genetic approaches to identifying additional genes and gene–environment interactions that constitute the many factors of orofacial clefts in this review.
Interdyscyplinarne leczenie rozszczepów wargi i/lub podniebienia – aktualny stan wiedzy
AbstractCleft lip and/or palate is one of the most common birth defects in the human population. It is responsible for 65% of craniofacial developmental anomalies, and the therapeutic procedure in this defect, due to the variety and complexity of problems that potentially result from it, can be extremely difficult. Numerous controversies concern both the surgical procedure itself, both primary and secondary, as well as rehabilitation, which in the simplest terms concerns maxillofacial conditions and speech. Over the last quarter of a century, there have been particularly many changes in the concept of treatment of orofacial clefts. This article presents them highlighting the most important new trends. With regard to the surgical treatment itself, the global tendency has been to shorten the date of primary surgical closure of the clefted palate. According to current standards, it should take place in the first year of a child’s life, which is related to both the development of pediatric anesthesiology and a modern view on speech and occlusion rehabilitation in this defect.
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.
