DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for anterior segment dysgenesis — screening already-approved drugs against its 12-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAnterior segment dysgenesis maps to a 12-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 anterior segment dysgenesis 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
retinol binding protein 4 (RBP4) — RBP4 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 {4-[2-(trifluoromethyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6QBA · 1.8 Å · ligand 2-[({4-[2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)amino]benzoic acid (2T1). Experimental structure, not a prediction.
What the evidence adds up to
Anterior segment dysgenesis is a spectrum of disorders caused by abnormal migration and differentiation of neural crest cells during embryogenesis. The periocular mesenchyme, which gives rise to structures such as the cornea and trabecular meshwork, is derived from neural crest cells and cranial paraxial mesoderm. Several genes involved in the migration and specification of these cells have been identified, including PITX2, FOXC1, and Tfap2b. Patients with anterior segment dysgenesis are susceptible to developing infantile glaucoma, congenital endothelial dystrophy, sclerocornea, and aniridia. There is overlapping genetic mutation between the anterior segment dysgenesis phenotypic spectrum and primary congenital glaucoma, since both involve abnormal development of Schlemm's canal and the drainage structures.
In a retrospective study of 220 eyes of 139 patients seen between 2002 and 2009, clinical diagnoses were Peters anomaly (72.7%), anterior staphyloma (11.4%), Rieger anomaly (7.7%), sclerocornea (6.4%), and others (1.8%). Visual acuity was measured in 61 patients. In bilaterally involved patients, best-corrected visual acuity in the better eye was 20/60 to 20/1000 (low vision) in 43.2% and less than 20/1000 (legally blind) in 24.3%. Fundus disorders were seen in 12 of 82 eyes examined (14.6%). Systemic abnormalities were present in 35 of 139 patients (25.2%), and a family history was present in 5 of 139 (3.6%). Of the 109 patients with Peters anomaly, 46.8% had bilateral disease, 27.5% had a normal fellow eye, and 25.7% showed other abnormal ocular findings in the fellow eye.
One review notes that new technologies for delivering drugs such as small molecules and biologics to the anterior segment are of growing interest, but the challenge remains to deliver effective drugs at therapeutic concentrations to targeted ocular tissue with minimal side effects. The review covers physiological and anatomical barriers to effective delivery, pathological conditions of the anterior segment, and unmet needs for treatment. No specific drug therapy for anterior segment dysgenesis itself is described in these abstracts. One letter discusses intracameral recombinant tissue plasminogen activator for refractory toxic anterior segment syndrome, a post-surgical inflammatory condition, not for anterior segment dysgenesis.
What is still missing is any clinical trial of a drug specifically intended to treat or reverse anterior segment dysgenesis. The literature remains descriptive of anatomy, genetics, and natural history. No therapy has been tested in patients for this condition. The barriers to progress include the lack of a clear drug target, the need for animal models that recapitulate the human disease, and the difficulty of designing a trial for a rare, heterogeneous disorder with variable visual 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.
Journal of Ocular Pharmacology and Therapeutics · 2013 · 96 citations
Anterior Eye Segment Drug Delivery Systems: Current Treatments and Future Challenges
AbstractNew technologies for delivery of drugs, such as small molecules and biologics, are of growing interest among clinical and pharmaceutical researchers for use in treating anterior segment eye disease. The challenge is to deliver effective drugs at therapeutic concentrations to the targeted ocular tissue with minimal side effects. To achieve this, a better understanding of the unmet needs, what is required of the various methods of delivery to achieve successful delivery, and the potential challenges of anterior segment drug delivery is necessary and the primarily aim of this review. This review covers the various physiological and anatomical barriers that exist for effective delivery to the targeted tissue of the eye, the pathological conditions of the anterior segment, and the unmet needs for treatment of these ocular diseases. Second, it reviews the novel delivery technologies that have the potential to maintain and/or improve the drug's therapeutic index and improving both patient adherence for chronic therapy and potential patient outcomes. This review bridges the pharmaceutical and clinical research/challenges and provides a detailed overview of anterior segment drug delivery accomplishments thus far, for researchers and clinicians.
Clinical Features of Anterior Segment Dysgenesis Associated With Congenital Corneal Opacities
AbstractPURPOSE: Anterior segment dysgenesis is one of the main causes of congenital corneal opacities. In this study, we investigated the clinical features and visual outcomes of patients with anterior segment dysgenesis in a large number of cases. METHODS: The medical records of patients with congenital corneal opacities in relation to anterior segment dysgenesis seen in the National Center for Child Health and Development, Japan, between April 2002 and October 2009, were retrospectively studied. RESULTS: Records of 220 eyes of 139 patients were reviewed. Mean follow-up period was 5 years. Clinical diagnoses were Peters anomaly (72.7%), anterior staphyloma (11.4%), Rieger anomaly (7.7%), sclerocornea (6.4%), and others (1.8%). Visual acuity was measured in 61 patients. The best-corrected visual acuity in the better eye of bilaterally involved patients was 20/60 to 20/1000 (low vision according to the International Classification of Diseases, Ninth Revision, Clinical Modification) in 43.2% and less than 20/1000 (legally blind) in 24.3%. Fundus examination was performed in 82 eyes, and disorders were seen in 12 (12 of 82; 14.6%). Systemic abnormalities were present in 35 patients (35 of 139; 25.2%); a family history was present in 5 patients (5 of 139; 3.6%). Of the 160 eyes of 109 patients with Peters anomaly, 51 patients (51 of 109; 46.8%) had bilateral Peters anomaly, 30 (30 of 109; 27.5%) had fellow eyes that were normal, and 28 (28 of 109, 25.7%) showed other abnormal ocular findings in the fellow eye. CONCLUSIONS: Anterior segment dysgenesis shows diverse clinical features, various severities of corneal opacities, and visual outcomes. Further understanding of the disease as an abnormality during embryogenesis and neural crest cell differentiations may be required.
Advances in Ophthalmology & Visual System · 2017 · 2 citations · open access
Update on Anterior Segment Development with Emphasis on Genetics and Correlation with Pathogenesis of Developmental & Primary Open Angle Glaucoma
AbstractThe ocular anterior segment structures are derived from periocular mesenchyme, which consists of neural crest cells and cranial paraxial mesoderm. Many embryological facts have been developed based on the fates of neural crest and mesoderm in mice and in chick. The interactions between the ocular mesenchyme and the surface ectoderm derived cells are also essential for the coordination of anterior segment development. These interactions are mediated by several transcription factors expressed in both the epithelial and mesenchymal cells and are being extensively studied. Anterior Segment dysgenesis (ASD) is a spectrum of disorders of variable phenotypic expressions caused by abnormal migration and differentiation of neural crest cells. Patients with ASD are susceptible to develop infantile glaucoma, congenital endothelial dystrophy, sclerocornea and aniridia. There has been an evident overlapping observation in the genetic mutations between the ASD phenotypic spectrum and glaucoma especially the primary congenital glaucoma (PCG) since it involves abnormal development of Schlemm's canal and the drainage structures. In this review, we are highlighting the steps in the embryological development of the anterior segment chamber structures. We also present the role of various transcription factors and link the above information to some of the genetic abnormalities, which are known in association with the pathogenesis of glaucoma.
Relationship Between Neural Crest Cell Specification and Anterior Segment Dysgenesis
AbstractDevelopment of the anterior segment of the eye is closely associated with neural crest cell migration and specification. Its development is complex as it requires the functioning of a combination of local factors, receptors, inductors, and signalling between tissues such as the optic cup and periocular mesenchyme (POM). POM is comprised of neural crest-derived mesenchymal progenitor cells that give rise to numerous important anterior segment structures such as the cornea, and trabecular meshwork. Several genes involved in the migration and specification of the POM have been identified, including PITX2, FOXC1, and Tfap2b. The author, with the help of Judith West-Mays and Vanessa Martino, has conducted an extensive literature search on recently published articles surrounding anterior segment dysgenesis and its associated genes and transcription factors in order to construct this review paper.
AbstractWe read an interesting ‘Clinical science’ article by Dotan et al 1 entitled ‘Intracameral recombinant tissue plasminogen activator (r-tPA) for refractory toxic anterior segment syndrome’. After studying the manuscript there are some issues that come to mind.
First, their prospective study was performed between May 2010 and November 2011. r-tPA was injected into patients …
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.
