DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for orofacial cleft 1 — screening already-approved drugs against its 14-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 1 maps to a 14-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 1 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
collagen type II alpha 1 chain (COL2A1) — COL2A1 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 p33drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5NIR · 1.74 Å · ligand 3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL (P33). Experimental structure, not a prediction.
What the evidence adds up to
Orofacial clefts affect roughly 1 in 1000 live births and are among the most common congenital head and neck anomalies worldwide. The condition is a complex trait with no single cause; both genetic and environmental factors contribute, and non-syndromic forms are more common than syndromic ones. Animal models and molecular studies have begun to identify candidate genes and loci, but the detailed mechanisms that bridge individual signalling pathways to the actual cleft remain elusive. One pathway repeatedly mentioned is Sonic hedgehog (Shh) signalling, which is indispensable for normal embryonic development; disruption of Shh signalling can result in a wide spectrum of craniofacial disorders including cleft lip, yet a precise causal chain from signalling failure to tissue defect has not been established.
Treatment for children with orofacial clefts is multidisciplinary and long-term. The main goals are functional and aesthetic rehabilitation of the soft tissues, jaw defect, and dentition, as well as ensuring normal speech without hypernasality and supporting psychosocial development. Dental and orthodontic procedures begin as early as 9 months to one year of age to prepare for later surgery. In the Czech Republic, care is centralised in specialised cleft centres in Prague and Brno, where orthodontic therapy is an integral part of the treatment protocol, coordinated with surgical reconstruction of the midface.
No drug therapy for orofacial clefts is described in any of these abstracts. The 2021 supplemental materials from a study in a developing country assess knowledge and attitudes of patients or parents toward orthodontic treatment, but no results or numbers are reported in the provided text. The 2010 paper is a review of orthodontic treatment phases and does not present new clinical data.
What is still missing is any clinical trial of a pharmacological intervention for orofacial cleft prevention or treatment. The basic biology of Shh and other pathways has not been translated into a tested drug. No patient stratification by genetic subtype has been used in a treatment trial. Funding for such translational work, and for trials that could test whether any existing drug might modulate the relevant signalling during development, remains absent from the published record.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
Česká stomatologie a praktické zubní lékařství · 2010 · 1 citations · open access
Orthodontic Treatment of a Patient with Facial Cleft (Part 1)
AbstractCĂlem lĂŠÄby pacientĹŻ postiĹženĂ˝ch rozĹĄtÄpem v orofaciĂĄlnĂ oblasti je funkÄnĂ a estetickĂĄ rehabilitace mÄkkĂ˝ch tkĂĄnĂ obliÄeje, defektu Äelisti a dentice. Na komplexnĂ lĂŠÄbÄ se v zĂĄvislosti na typu a rozsahu defektu, postnatĂĄlnĂm vĂ˝voji a zdravotnĂm stavu postiĹženĂŠho dĂtÄte podĂlĂ tĂ˝m specialistĹŻ, jehoĹž interdisciplinĂĄrnĂ pĂŠÄe je soustĹedÄna do specializovanĂ˝ch rozĹĄtÄpovĂ˝ch center. V ÄeskĂŠ republice majĂ dlouholetou tradici pracoviĹĄtÄ v Praze a v BrnÄ. NedĂlnou souÄĂĄstĂ lĂŠÄebnĂŠho protokolu je ortodontickĂĄ terapie. NĂĄsledujĂcĂ sdÄlenĂ je shrnutĂm nejdĹŻleĹžitÄjĹĄĂch fĂĄzĂ ortodontickĂŠ lĂŠÄby v nĂĄvaznosti na chirurgickĂŠ rekonstrukce stĹednĂ obliÄejovĂŠ etĂĄĹže.
IP International Journal of Medical Paediatrics and Oncology · 2020 · 1 citations · open access
Orofacial clefts in children and its management
AbstractOrofacial cleft is one of the commonest congenital irregularities which impacts adversely on the life of the individual and to an enormous degree influences the family. Brought about by the collaboration of ecological and hereditary variables, this variation from the norm realizes diminished personal satisfaction. The board of this irregularity involves a group including a split specialist, language teacher, dental specialist, orthodontists, etc. In this review article we will learn about causes, risk factors and various treatment.
Cleft Lip and Palate in Children: Classification and Treatment
AbstractOrofacial clefts are one of the most common head and neck birth defects worldwide, affecting children of all socioeconomic and cultural backgrounds. Orofacial clefts refer to a cleft lip and palate, a complex trait caused by multiple genetic and environmental factors. Children with orofacial clefts commonly have various issues, such as learning difficulties, speech and language disorders, middle ear abnormalities, psychosocial problems, and dental abnormalities. Due to the complex nature of a cleft lip/palate, the treatment involves interdisciplinary teams, including plastic surgeons, pediatric dentists, maxillofacial surgeons, orthodontists, and speech therapists. Dental and orthodontic procedures are required at an early age (9 months to one year of age) to aid normal facial and dental development and prepare the patient for surgery later. The main treatment goals in cleft lip and palate cases are to maintain the natural anatomical form of the lips and palate to ensure everyday speech without hypernasality. An additional goal is to ensure normal psychosocial development.
Supplemental Material, sj-docx-1-cpc-10.1177_1055665621998179 - Cleft Care in a Developing Country: An Assessment of Knowledge and Attitudes of Patients/Parents of Children With an Orofacial Cleft to Orthodontic Treatment
AbstractSupplemental Material, sj-docx-1-cpc-10.1177_1055665621998179 for Cleft Care in a Developing Country: An Assessment of Knowledge and Attitudes of Patients/Parents of Children With an Orofacial Cleft to Orthodontic Treatment by Oluranti Olatokunbo daCosta, Ikenna Gerald Isiekwe and Chetachi Mariagoretti Ogbonna in The Cleft Palate-Craniofacial Journal
Supplemental Material, sj-pdf-1-cpc-10.1177_1055665621998179 - Cleft Care in a Developing Country: An Assessment of Knowledge and Attitudes of Patients/Parents of Children With an Orofacial Cleft to Orthodontic Treatment
AbstractSupplemental Material, sj-pdf-1-cpc-10.1177_1055665621998179 for Cleft Care in a Developing Country: An Assessment of Knowledge and Attitudes of Patients/Parents of Children With an Orofacial Cleft to Orthodontic Treatment by Oluranti Olatokunbo daCosta, Ikenna Gerald Isiekwe and Chetachi Mariagoretti Ogbonna in The Cleft Palate-Craniofacial Journal
Science Journal of Clinical Medicine · 2016 · 0 citations · open access
A Century of Cleft Treatment- An Orthodontic Perspective
AbstractOrofacial clefting is the most common congenital deformity. Its treatment is a long drawn process with various challenges. However, successful completion of treatment is highly satisfying not just to the patient but also the team of specialists involved with it. The following article provides an overview of the evolution of cleft treatment over the past century. It briefly describes the changing views of the orthodontic specialty towards the diagnosis and treatment of this deformity over the past century. Its gradual process from the rudimentary treatment protocols of the early 20th century to the holistic approach followed currently.
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.
