DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for primary failure of tooth eruption — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePrimary failure of tooth eruption maps to a 2-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 primary failure of tooth eruption 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
myosin light chain 3 (MYL3) — MYL3 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 adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9TPJ · 3.02 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
Primary failure of tooth eruption is a rare condition that predominantly affects molar dentition and leads to posterior open bites. It is difficult to diagnose and difficult to treat. Traditional orthodontic treatments are ineffective because the teeth do not respond to physiological eruption forces despite the absence of any physical obstruction. In a 37-year-old adult case, restorative management alone, without surgical or orthodontic intervention, achieved successful functional and aesthetic outcomes. The condition has variable presentation, and a family history of tooth eruption problems is common, suggesting a significant genetic component.
Genetic studies have focused on the parathyroid hormone 1 receptor (PTH1R) gene, mutations in which are associated with primary failure of eruption. The condition exists without systemic involvement, distinguishing it from syndromic eruption disorders such as cleidocranial dysostosis or Trisomy 21. Hypodontia occurs more frequently in affected individuals. The basic physiology of tooth eruption involves serial and reciprocal gene expressions, but no pharmaceutical intervention has been developed to address eruption disorders.
A retrospective study of forced eruption in 468 impacted teeth (371 patients) found that age significantly differed between success and failure groups. Factors affecting treatment duration were apex formation, tooth position, rotation, and re-operation. Re-operation had a 96% success rate, and the average orthodontic treatment duration for re-operated teeth was 20.36 months, about 9 months shorter than the overall average of 29.99 months. Causes of forced eruption failure in 6 cases were ankylosis (3 cases), incomplete alignment with the dental arch (2 cases), and significant deviation in tooth location (1 case). No drug therapy was tested in any of these studies.
What is still missing is any clinical trial of a pharmaceutical agent for primary failure of eruption, a clear patient stratification method beyond genetic testing for PTH1R mutations, and funding for research into the underlying molecular mechanisms that might one day be targeted. The condition remains managed by surgical, orthodontic, or restorative means, with unpredictable outcomes.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
International Journal of Applied and Basic Medical Research · 2018 · 10 citations · open access
Failure of eruption of permanent tooth
AbstractPrimary failure of eruption (PFE) is a rare condition that can lead to posterior open bites. It is difficult to diagnose and difficult to treat. PFE appears to be a condition that predominantly affects the molar dentition. The increased frequency of hypodontia in affected individuals and common findings of a family history regarding tooth eruption problems suggests a significant genetic component to the etiology of this rare condition.
Genetic analysis of familial non-syndromic primary failure of eruption
AbstractWhile some eruption disorders occur as part of a medical syndrome, primary failure of eruption (PFE) – defined as a localized failure of secondary tooth eruption -exists without systemic involvement. Recent studies support that heredity may play an important role in the pathogenesis of PFE. The objective of our human genetic study is to investigate the genetic contribution to PFE.
AbstractBasic biomedical sciences form foundation for enlightened rational clinical practice and provide substance for innovation and advance. Tooth eruption is highly complex yet finely regulated process of developmental biology. Integration of local, regional and systemic mechanisms is uniquely displayed in eruption physiology. Serial and reciprocal gene expressions in the process enable parallel progress of opposite biologic process in close proximity. Rational clinical address to eruption disorders can only be based on sound understanding of basic physiologic process. Scope for developing enhanced therapeutic capabilities and pharmaceuticals must emerge through understanding and investigation on the perspectives. This review attempts to briefly present simplified view of physiology of tooth eruption drawn on the current understanding.
Archives of Medicine and Health Sciences · 2016 · 2 citations · open access
Primary failure of eruption
AbstractPrimary failure of eruption (PFE) is a partially understood oral condition associated with tooth eruption failure. Failure of eruption may affect one or a number of teeth, in either the primary or the permanent dentition, and depending on the underlying etiology, it can be partial or complete absence of teeth in oral cavity. For proper diagnosis, the differential diagnosis of PFE should always begin with the exclusion of potential systemic and local factors which can affect the eruption of teeth.
Journal of Healthcare Sciences · 2025 · 1 citations · open access
Tooth Eruption Disorders from Delayed Eruption to Ectopic Eruption Management
AbstractTooth eruption is a highly coordinated biological process that allows teeth to migrate from their developmental positions within the jawbone to their functional positions in the oral cavity. Disruption of this process can lead to a range of clinical anomalies, including delayed eruption, ectopic eruption, and primary failure of eruption (PFE). These anomalies present significant clinical challenges due to their profound implications for occlusal development, periodontal health, and overall patient quality of life. The etiology of eruption anomalies is multifactorial, encompassing local mechanical obstructions (retained deciduous teeth, odontomas, fibrous hyperplastic tissue), systemic disturbances (endocrine or nutritional deficiencies), and genetic conditions such as cleidocranial dysostosis, Trisomy 21, and mutations in the parathyroid hormone 1 receptor (PTH1R) gene associated with PFE. Ectopic eruptions, commonly affecting the first permanent molars and maxillary canines, can result in root resorption of adjacent teeth, arch length deficiencies, and long-term malocclusions if not detected early. Meanwhile, PFE is a rare clinical entity wherein teeth fail to respond to the physiological forces of eruption despite the absence of any physical obstruction, making traditional orthodontic treatments ineffective. This review analyzes the pathogenesis, clinical presentation, and diagnostic advances associated with delayed and ectopic eruption and PFE, while evaluating available treatment approaches, ranging from interceptive and surgical interventions to prosthodontic rehabilitation. Emphasis is placed on early detection, multidisciplinary collaboration, and personalized clinical planning to optimize outcomes. By synthesizing recent evidence, this review aims to guide clinicians in effectively managing eruption anomalies, highlighting the role of early intervention, precision diagnosis, and long-term patient monitoring.
Replacing buried teeth: A Review of primary failure of eruption of permanent teeth and case report
AbstractPrimary failure of eruption is a condition that has variable presentation and can be difficult to diagnose. This article provides an overview of the condition and discusses the management of an unusual case of primary failure of eruption of permanent teeth in a 37-year-old adult. CPD/Clinical Relevance: Where surgical and orthodontic options are unpredictable, restorative management alone may achieve successful functional and aesthetic outcomes for cases involving primary failure of eruption of permanent teeth.
Forced eruption in impacted teeth: analysis of failed cases and outcome of re-operation
AbstractAbstract Background Forced eruption of an impacted tooth usually requires surgical and orthodontic interventions to successfully bring the tooth into the dental arch. The clinical time required for a forced eruption is difficult to predict before treatment begins and success rates are affected by several factors before and after an eruption. This study was conducted to identify factors that affect the success of forced eruption, the duration of orthodontic treatment of impacted teeth, and the reasons for re-operation and forced eruption failure in a various teeth and cases. Methods In this retrospective study, the records regarding the forced eruption of 468 teeth in 371 patients from June 2006 to May 2020 at the Advanced General Dentistry Department of Yonsei University Dental Hospital were initially examined. The records of 214 teeth in 178 patients who completed orthodontic treatment were included in the analysis. Data on patient demographics, tooth characteristics, orthodontic treatment duration, re-operations, and failures were collected from electronic medical records. Results There was a significant difference in age between the success and failure forced eruption. Factors significantly affecting treatment duration were apex formation, position, rotation, and re-operation. Re-operation had a 96% success rate. The average orthodontic treatment duration was 29.99 ± 16.93 months, but the average orthodontic treatment duration for teeth that undergone re-operation was 20.36 ± 11.05 months, which was approximately 9 months shorter. Additionally, there was an interaction effect between rotation and re-operation on the duration of orthodontic treatment. The causes for failure of forced eruption in 6 cases were ankyloses (3 cases), incomplete alignment with the normal dental arch (2 cases), and a significant deviation in the impacted tooth’s location (1 case). Conclusions To increase the success rate of forced eruption, age should be considered as a priority, and in order to predict the treatment period, the apex formation status, position in the arch, and rotation should be considered in addition to age. When determining re-operation, considering factors such as ankylosis, root curvature, and apex formation can help in the success of orthodontic treatment.
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.
