DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for iris disorder — screening already-approved drugs against its 20-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleIris disorder maps to a 20-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 iris disorder 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
endoplasmic reticulum aminopeptidase 1 (ERAP1) — ERAP1 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 pgedrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6RQX · 1.68 Å · ligand TRIETHYLENE GLYCOL (PGE). Experimental structure, not a prediction.
What the evidence adds up to
The 2005 review of immune reconstitution inflammatory syndrome (IRIS) in HIV describes a condition where mycobacterial or cryptococcal disease accounts for roughly 30% of cases each, with proposed clinical definitions lacking prospective validation. The authors note that supportive care is usually sufficient unless symptoms are prolonged or life-threatening, and that blood tests such as CD4 count or viral load may be unreliable because the immune response can be compartmentalised to specific tissues like the brain. This abstract contains no data on iris disorders and offers no therapeutic intervention relevant to them.
A 1976 case series reports seven patients with iris nodules in essential iris atrophy, described as small yellow nodules appearing late in the disease that progressively increase in number and darken to brown. The differential diagnosis listed includes neurofibromatosis, melanomas, inflammatory nodules, and iridocorneal dysgenesis. No treatment or outcome data are provided, and the report is purely descriptive.
The 2017 study of a dominant-negative PIK3R1 mutation in SHORT syndrome used knock-in mice and two human subjects. In mice, OCT showed significantly decreased iris thickness and width with increased pupil area and irregular shape, while overall eye development, corneal clarity, anterior chamber volume, intraocular pressure, and retinal structure were normal. Both human subjects had Rieger anomaly with thin irides, irregular pupils, a prominent Schwalbe ring, goniosynechiae, early cataracts, and glaucoma, but no diabetic retinopathy despite over 30 years of diabetes. The study establishes a developmental role for PI3K in iris formation but offers no treatment.
The 2025 review of congenital aniridia identifies PAX6 pathogenic variants as the primary genetic cause, with additional implicated genes including FOXC1, PITX2, CYP1B1, FOXD3, PITX3, CPAMD8, ITPR1, TENM3, TRIM44, COL4A1, CRYAA, and PXDN. Differential diagnoses include WAGR syndrome, Axenfeld-Rieger syndrome, ring-chromosome 6 syndrome, COL4A1-related anterior segment dysgenesis, Gillespie syndrome, and Peters anomaly. The authors recommend genetic testing combined with clinical features such as iris anomalies, keratopathy, cataracts, glaucoma, foveal hypoplasia, nystagmus, and optic nerve head abnormalities. No quantitative outcomes or therapeutic results are reported.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Infectious Diseases · 2005 · 148 citations
Immune reconstitution inflammatory syndrome in HIV
AbstractPURPOSE OF REVIEW: The purpose of this review is to describe the epidemiology, clinical features, putative immune mechanisms and management of immune reconstitution inflammatory syndrome (IRIS) using data published in the last 2 years. RECENT FINDINGS: Ever more conditions are reported as IRIS events. These most frequently occur with mycobacterial (tuberculosis or Mycobacterium avium complex infection) or cryptococcal disease (each in approximately 30% of cases). Definitions have been proposed for its clinical diagnosis. These suffer from a lack of prospective studies to support their predictive value. The immunopathogenesis of IRIS appears to be related to the interaction between HAART-induced changes in host immune response and the presence of (usually microbial) antigen. Increasing evidence exists that this might be an anatomically compartmentalized phenomenon, such that immune responses may be localized to specific tissue sites such as the brain. This has implications for the use of simple blood tests, such as CD4 count or change in viral load, when assessing risk of IRIS. Treatment options include immune modulation, though supportive care is typically all that is required, unless symptoms are prolonged, significant or life-threatening. SUMMARY: IRIS is common and will become more so as HAART is rolled out worldwide. Clear clinical definitions are required to avoid its over-diagnosis due to misclassification of other conditions.
AbstractSeven cases are reported, believed to be the first in the literature, in which iris nodules are verified in the complete spectrum of essential iris atrophies. This feature appears late in the course of the disease as small yellow nodules that progressively increase in number and gradually become dark brown. The differential diagnosis of multiple iris nodules includes neurofibromatosis, melanomas, inflammatory nodules, and developmental anomalies such as iridocorneal dysgenesis.
Iris Malformation and Anterior Segment Dysgenesis in Mice and Humans With a Mutation in PI 3-Kinase
AbstractPurpose: To determine the ocular consequences of a dominant-negative mutation in the p85α subunit of phosphatidylinositol 3-kinase (PIK3R1) using a knock-in mouse model of SHORT syndrome, a syndrome associated with short stature, lipodystrophy, diabetes, and Rieger anomaly in humans. Methods: We investigated knock-in mice heterozygous for the SHORT syndrome mutation changing arginine 649 to tryptophan in p85α (PIK3R1) using physical examination, optical coherence tomography (OCT), tonometry, and histopathologic sections from paraffin-embedded eyes, and compared the findings to similar investigations in two human subjects with SHORT syndrome heterozygous for the same mutation. Results: While overall eye development was normal with clear cornea and lens, normal anterior chamber volume, normal intraocular pressure, and no changes in the retinal structure, OCT images of the knock-in mouse eyes revealed a significant decrease in thickness and width of the iris resulting in increased pupil area and irregularity of shape. Both human subjects had Rieger anomaly with similar defects including thin irides and irregular pupils, as well as a prominent ring of Schwalbe, goniosynechiae, early cataract formation, and glaucoma. Although the two subjects had had diabetes for more than 30 years, there were no signs of diabetic retinopathy. Conclusions: A dominant-negative mutation in the p85α regulatory subunit of PI3K affects development of the iris, and contributes to changes consistent with anterior segment dysgenesis in both humans and mice.
Ophthalmology and Therapy · 2025 · 9 citations · open access
Comprehensive Analysis of Congenital Aniridia and Differential Diagnoses: Genetic Insights and Clinical Manifestations
AbstractINTRODUCTION: Congenital aniridia (CA) is a severe and complex disorder involving the entire eye, primarily characterized by iris anomalies alongside other clinical features that pose significant risks to vision. This study seeks to offer a comprehensive overview of CA by detailing its clinical presentations, genetic underpinnings, associated phenotypes, and differential diagnoses. Additionally, it proposes a diagnostic framework to distinguish CA from other conditions that present with similar iris abnormalities. METHODS: We conducted a comprehensive literature review to compile and analyze clinical and genetic data related to CA and its differential diagnoses. We included all studies describing the clinical characteristics, pathogenic variants, and associated syndromes of congenital aniridia. RESULTS: CA presents a wide range of ocular symptoms. Pathogenic variants in the PAX6 gene are the primary genetic cause of CA, though variations in other genes, including FOXC1, PITX2, CYP1B1, FOXD3, PITX3, CPAMD8, ITPR1, TENM3, TRIM44, COL4A1, CRYAA, and PXDN may also be implicated. The differential diagnosis of CA requires careful consideration of conditions with overlapping symptoms, such as WAGR syndrome (which involves deletions affecting the PAX6 and WT1 genes on chromosome 11p13, and potentially BDNF on 11p14.1), Axenfeld-Rieger syndrome (FOXC1/PITX2), ring-chromosome 6 syndrome (which involves FOXC1 microdeletion), COL4A1-related anterior segment dysgenesis, Gillespie syndrome (ITPR1 gene) or Peters anomaly. Accurate diagnosis can be achieved by evaluating specific clinical features-including iris anomalies, aniridia-associated keratopathy, cataracts, glaucoma, foveal hypoplasia, nystagmus, and optic nerve head abnormalities-supplemented by genetic testing. CONCLUSIONS: Understanding the diverse clinical presentations and genetic basis of diseases associated with iris abnormalities is essential for accurate diagnosis and effective management. Integrating genetic diagnostics into the evaluation process enables the development of tailored treatment strategies, which can significantly improve patient outcomes.
An Alternative Hypothesis for Iris Maldevelopment (Aniridia)
AbstractTwo principal hypotheses for the pathogenesis of hypoplastic iris development ("aniridia") have been proposed: 1) the ectodermal theory, positing incomplete elaboration of the cup, resulting in an absence of framework for further development; and 2) the "mesodermal" theory, wherein inadequate migration or proliferation of mesenchymal elements is proposed. Two eyes of two patients with persistent "anterior leaf" iris strand remnants which traverse the pupillary space are reported. They are differentiated from the previously described persistent tunica vasculosa lentis. The presence of a persistent pupillary iris strand suggests portions of the iris may have formed and inappropriately regressed. Recent work in cell biology highlights the importance of remodeling and cell death in revealing ultimate phenotypic expression. This alternative hypothesis suggests that aniridia may be explained in part on the basis of excessive remodeling and cell death.
Clinical and Experimental Obstetrics & Gynecology · 2017 · 0 citations · open access
Changes in irisin levels in patients with hyperemesis gravidarum
AbstractPURPOSE: The aim of this study was to compare levels of serum irisin in hyperemesis gravidarum (HG) patients to healthy gravidas. MATERIALS AND METHODS: Twenty pregnant women with hyperemesis gravidarum (Group 1) and 20 healthy pregnant women (Group 2) all of similar ages, body mass index, and all at similar pregnancy development comprised the study cohort. Fasting serum samples were obtained and measured for irisin levels. Comparisons between groups were done by Mann Whitney U (MWU) test and p < 0.05 was considered as statistically significant. RESULTS: All the patients in groups 1 and 2 were primigravid and age, gestational week, and body mass index values were similar. No statistically significant difference were present among these parameters (p > 0.05, MWU test). The plasma irisin concentrations in group 1 were significantly higher (irisin (average ±S D): 116.9 ± 32.3 ng/ml vs. 87.7 ± 26.2 ng/ml) compared to the control group. CONCLUSION: This study suggests a possible role of irisin, which might be involved in the pathology of HG.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works using Disease Ontology synonyms, resolved on OpenAlex.
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