DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for orofacial cleft 8 — 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 8 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 8 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
tumor protein p63 (TP63) — TP63 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7Z7E · 1.8 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
No drug is tested or proposed for orofacial cleft 8 in these abstracts. The 2020 review states that many non-syndromic orofacial clefts result from extrinsic factors, genetic susceptibilities, and their interactions, and it examines molecular mechanisms of environmental factors that may protect against or increase risk. The 2015 review notes that Shh signalling is indispensable for normal embryonic development and that its disruption can cause cleft lip, but it also says a detailed mechanism bridging individual signalling pathways to cleft lip is still elusive. No quantitative outcomes such as survival or response rates are reported in any of these papers.
The 2010 and 2023 papers describe standard care: interdisciplinary teams including plastic surgeons, orthodontists, and speech therapists, with orthodontic therapy beginning as early as 9 months to one year of age. The 2023 paper lists common issues in affected children — learning difficulties, speech and language disorders, middle ear abnormalities, psychosocial problems, and dental abnormalities — and states that treatment goals are to maintain natural anatomical form and ensure everyday speech without hypernasality. The 2022 commentary warns that patients with cleft lip and/or palate undergo multiple reconstructive surgeries from infancy to adulthood and that the long-term effects of perioperative opioid prescriptions should concern all team members; it summarises evidence-based strategies to minimise opioid use. The 2023 review of presurgical infant orthopaedic protocols says these are applied before surgery to facilitate repair by restoring alar base and maintaining skeletal and soft tissue harmony, and that craniofacial orthodontists can choose from a wide array of treatment options.
No drug intervention for orofacial cleft 8 is mentioned. What is missing is any preclinical or clinical trial of a pharmacological agent for this specific cleft subtype, as well as patient stratification by genetic or environmental risk factors that might allow targeted prevention or therapy. Funding for such trials and for the basic research needed to identify druggable pathways in orofacial cleft 8 has not been reported in 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.
Neurology · 2008 · 172 citations
Does lamotrigine use in pregnancy increase orofacial cleft risk relative to other malformations?
AbstractOBJECTIVE: To investigate whether first trimester exposure to lamotrigine (LTG) monotherapy is specifically associated with an increased risk of orofacial clefts (OCs) relative to other malformations, in response to a signal regarding increased OC risk. METHODS: Population-based case-control study with malformed controls based on EUROCAT congenital anomaly registers. The study population covered 3.9 million births from 19 registries 1995-2005. Registrations included congenital anomaly among livebirths, stillbirths, and terminations of pregnancy following prenatal diagnosis. Cases were 5,511 nonsyndromic OC registrations, of whom 4,571 were isolated, 1,969 were cleft palate (CP), and 1,532 were isolated CP. Controls were 80,052 nonchromosomal, non-OC registrations. We compared first trimester LTG and antiepileptic drug (AED) use vs nonepileptic non-AED use, for mono and polytherapy, adjusting for maternal age. An additional exploratory analysis compared the observed and expected distribution of malformation types associated with LTG use. RESULTS: There were 72 LTG exposed (40 mono- and 32 polytherapy) registrations. The ORs for LTG monotherapy vs no AED use were 0.67 (95% CI 0.10-2.34) for OC relative to other malformations, 0.80 (95% CI 0.11-2.85) for isolated OC, 0.79 (95% CI 0.03-4.35) for CP, and 1.01 (95% CI 0.03-5.57) for isolated CP. ORs for any AED use vs no AED use were 1.43 (95% CI 1.03-1.93) for OC, 1.21 (95% CI 0.82-1.72) for isolated OC, 2.37 (95% CI 1.54-3.43) for CP, and 1.86 (95% CI 1.07-2.94) for isolated CP. The distribution of other nonchromosomal malformation types with LTG exposure was similar to non-AED exposed. CONCLUSION: We find no evidence of a specific increased risk of isolated orofacial clefts relative to other malformations due to lamotrigine (LTG) monotherapy. Our study is not designed to assess whether there is a generalized increased risk of malformations with LTG exposure.
Birth Defects Research · 2020 · 56 citations · open access
Environmental mechanisms of orofacial clefts
AbstractOrofacial clefts (OFCs) are among the most common birth defects and impart a significant burden on afflicted individuals and their families. It is increasingly understood that many nonsyndromic OFCs are a consequence of extrinsic factors, genetic susceptibilities, and interactions of the two. Therefore, understanding the environmental mechanisms of OFCs is important in the prevention of future cases. This review examines the molecular mechanisms associated with environmental factors that either protect against or increase the risk of OFCs. We focus on essential metabolic pathways, environmental signaling mechanisms, detoxification pathways, behavioral risk factors, and biological hazards that may disrupt orofacial development.
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.
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.
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.
Perspectives of the ASHA Special Interest Groups · 2022 · 0 citations
The Use of Opioids in the Surgical Care of Patients With Orofacial Clefts: A Commentary and Guide to Management
AbstractPurpose: This commentary outlines the surgical pathway for patients with cleft lip and/or palate (CLP), identifies risks associated with opioid prescribing in this patient population, and summarizes strategies to safely minimize the need for perioperative opioid prescribing. Conclusions: Patients with orofacial clefts, CLP, undergo multiple reconstructive surgeries. The long-term effects of perioperative opioid prescriptions should concern all members of the cleft and craniofacial team. The amount of surgery each patient with a CLP may face varies by patient and can begin in infancy and continue to adulthood. In this commentary, the surgical pathway for CLP is reviewed, and the opioid crisis is addressed in regard to this vulnerable patient group. Solutions for cleft and craniofacial team members from evidence-based literature are summarized to minimize the use of opioids prescribed in this patient population. Approaches to reduce opioid use after CLP surgery are holistic and multidisciplinary.
IntechOpen eBooks · 2023 · 0 citations · open access
Protocols in Presurgical Infant Orthopaedic Treatment—An Evidence Based Review
AbstractPresurgical infant orthopaedic (PSIO) protocol is applied prior to cleft Lip and/cleft palate surgical intervention to facilitate the repair by restoring the alar base and maintaining the skeletal, soft tissue harmony. The objective of this review is to assess the literature on the presurgical infant orthopaedic protocol most widely used and accepted. Searches were made in PubMed, Cochrane and Google Scholar on cleft lip and/palate. A large number of articles documented approaching PSIO for cleft treatment with the intent to provide a satisfactory treatment for cleft patients, requiring far more than just correctional surgery and its ability to do so is unique. Craniofacial Orthodontists can choose from a wide array of treatment options for their patients and can learn from the outcomes attained by applying a combination of outcomes at various other centers.
Journal of Dr. YSR University of Health Sciences. · 2013 · 0 citations
Management of oronasal fissure in an adolescent with cleft lip and palate
AbstractSuccessful treatment of cleft lip and palate requires a multidisciplinary approach from birth to adulthood. This article discusses the problem based diagnosis and treatment approach in an adolescent with a repaired cleft lip and untreated cleft palate. A treatment plan was developed to address the chief complaint of the patient. Maxillary expansion was done with a bonded hyrax screw rather than a quad helix, so as to shorten the pre-surgical treatment time followed by surgical closure of the oronasal fissure.
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.
