DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for retinoschisis — screening already-approved drugs against its 36-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleRetinoschisis maps to a 36-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 retinoschisis 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
protein tyrosine phosphatase receptor type B (PTPRB) — PTPRB 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 tert-butoxycarbonyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2I4G · 1.65 Å · ligand N-(TERT-BUTOXYCARBONYL)-L-TYROSYL-N-METHYL-4-(SULFOAMINO)-L-PHENYLALANINAMIDE (UA1). Experimental structure, not a prediction.
What the evidence adds up to
Retinoschisis in patients with pars planitis was bilateral in all 34 cases reviewed, and 13 eyes (19%) developed retinoschisis. In six patients (86%) the schisis was bilateral. Average best-corrected visual acuity at last follow-up was 20/22, with an average follow-up of seven years. Schisis developed or progressed in patients with both active and inactive inflammation. Five eyes of five patients underwent vitrectomy; three for disease control with scleral buckle to reduce residual traction, and two for retinal detachment with progressive schisis despite inactive uveitis. Seven eyes remained stable without intervention.
A retrospective analysis of 263 patients (372 eyes) over age 18 found retinoschisis in 1.1% of examined patients. In uncomplicated cases, bilateral changes occurred in 35% and unilateral in 65%; in complicated cases, bilateral in 44.5% and unilateral in 55.5%. Ametropia distribution was equal: 21.5% myopia and emmetropia, 57% hypermetropia. Retinoschisis was diagnosed in the lower temporal quadrant in 58% of cases. The condition was nearly twice as common in female patients, mainly with hypermetropia and aged 50–70 years.
Laboratory investigation of the molecular relationship between retinoschisis (RS1 gene) and Norrie disease (NDP gene) found no direct protein-protein interaction between retinoschisin and norrin by co-immunoprecipitation and mass spectrometry. However, STRING database analysis suggested a potential indirect functional association, possibly through the FZD4 protein interactome via PLIN2 and the MAP kinase signalling pathway. The exact molecular link remains unknown.
What is still missing are prospective trials that stratify patients by aetiology (inflammatory, degenerative, or X-linked genetic), standardised outcome measures beyond visual acuity, and funding for mechanistic studies that could identify drug targets. No drug has been tested in any of these cohorts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Ocular Immunology and Inflammation · 2016 · 21 citations
Retinoschisis in Pars Planitis
AbstractPURPOSE: To describe the course of retinoschisis in patients with pars planitis (PP). METHODS: Chart review of PP patients seen July 2012-September 2014 at a single institution. RESULTS: Included were 34 patients (68 eyes). Uveitis was bilateral in all cases. Thirteen eyes (19%) developed retinoschisis. In six patients (86%), the schisis was bilateral. The average follow-up of patients with schisis was 7 years; the average best-corrected visual acuity (BCVA) was 20/22 at last follow-up. Schisis was noted to develop or progress in patients with both active and inactive inflammation. Five eyes of five patients underwent vitrectomy; three for disease control, with scleral buckle to reduce residual traction. Two eyes required vitrectomy for retinal detachment with progressive schisis, despite inactive uveitis. Seven eyes remained stable without intervention. CONCLUSIONS: Retinoschisis is a common complication in patients with PP. It is typically bilateral, and may develop or progress, despite control of uveitis.
BMC Research Notes · 2021 · 3 citations · open access
Retinoschisis and Norrie disease: a missing link
AbstractOBJECTIVE: Retinoschisis and Norrie disease are X-linked recessive retinal disorders caused by mutations in RS1 and NDP genes respectively. Both are likely to be monogenic and no locus heterogeneity has been reported. However, there are reports showing overlapping features of Norrie disease and retinoschisis in a NDP knock-out mouse model and also the involvement of both the genes in retinoschisis patients. Yet, the exact molecular relationships between the two disorders have still not been understood. The study investigated the association between retinoschisin (RS1) and norrin (NDP) using in vitro and in silico approaches. Specific protein-protein interaction between RS1 and NDP was analyzed in human retina by co-immunoprecipitation assay and MALDI-TOF mass spectrometry. STRING database was used to explore the functional relationship. RESULT: Co-immunoprecipitation demonstrated lack of a direct interaction between RS1 and NDP and was further substantiated by mass spectrometry. However, STRING revealed a potential indirect functional association between the two proteins. Progressively, our analyses indicate that FZD4 protein interactome via PLIN2 as well as the MAP kinase signaling pathway to be a likely link bridging the functional relationship between retinoschisis and Norrie disease.
Ophthalmology and Therapy · 2020 · 2 citations · open access
Adult Presentation of X-Linked Retinoschisis: Patient and Physician Perspectives
AbstractThis commentary article is co-authored by an adult patient with X-linked retinoschisis and two ophthalmologists affiliated with the University Hospitals Birmingham NHS Foundation Trust. It describes the patient's experiences of sight loss and the diagnosis and management of X-linked retinoschisis. The treating ophthalmologists then draw upon these experiences and discuss the disease and associated sight loss in a wider context.
Modern technologies in ophtalmology · 2023 · 0 citations
Features of the course of retinoschisis in patients of the Republic of Buryatia
AbstractIt is known that the formation of retinoschisis occurs at any age, the senile form is more common, with the same probability in men and women. However, data on the nature of retinoschisis and their prevalence in patients over 18 years of age are fragmentary and unsystematic. Material and methods. A retrospective analysis of the occurrence of retinoschisis in patients older than 18 years was carried out. Results. Retinoschisis was diagnosed in 263 patients (372 eyes), which was 1.1 % of the number of examined patients. Group I included patients with uncomplicated retinoschisis, and group II included patients with complicated retinoschisis. In group I, bilateral changes were observed in 35 % of cases, and unilateral changes were observed in 65 %. In group II, bilateral changes were diagnosed in 44.5 % of cases, unilateral – 55.5 %. The distribution by type of ametropia was equal in both groups: 21.5 % of patients had myopia and emmetropia, in 57 % of cases – hypermetropia. According to the location in both groups, retinoschisis was diagnosed more often in the lower temporal quadrant in 58 % of cases. Conclusion. Retinoschisis is almost 2 times more common in female patients, mainly with hypermetropia and at the age of 50–70 years. In all types of ametropia, retinoschisis was localized in the lower temporal quadrant in 58 % of cases. Keywords: retinoschisis, retinal detachment, retinal hole, laser coagulation
AbstractAbstract Objective Retinoschisis and Norrie disease are X-linked recessive retinal disorders caused by mutations in RS1 and NDP genes respectively. Both are likely to be monogenic and no locus heterogeneity has been reported. However, there are reports showing overlapping features of Norrie disease and retinoschisis in a NDP knock-out mouse model and also the involvement of both the genes in retinoschisis patients. Yet, the exact molecular relationships between the two disorders have still not been understood. The study investigated the association between retinoschisin (RS1) and norrin (NDP) using in vitro and in silico approaches. Specific protein–protein interaction between RS1 and NDP was analyzed in human retina by co-immunoprecipitation assay and MALDI-TOF mass spectrometry. STRING database was used to explore the functional relationship. Result Co-immunoprecipitation demonstrated lack of a direct interaction between RS1 and NDP and was further substantiated by mass spectrometry. However, STRING revealed a potential indirect functional association between the two proteins. Progressively, our analyses indicate that FZD4 protein interactome via PLIN2 as well as the MAP kinase signaling pathway to be a likely link bridging the functional relationship between retinoschisis and Norrie disease.
AbstractAbstract Objective Retinoschisis and Norrie disease are X-linked recessive retinal disorders caused by mutations in RS1 and NDP genes respectively. Both are likely to be monogenic and no locus heterogeneity has been reported. However, there are reports showing overlapping features of Norrie disease and retinoschisis in a NDP knock-out mouse model and also the involvement of both the genes in retinoschisis patients. Yet, the exact molecular relationships between the two disorders have still not been understood. The study investigated the association between retinoschisin (RS1) and norrin (NDP) using in vitro and in silico approaches. Specific protein–protein interaction between RS1 and NDP was analyzed in human retina by co-immunoprecipitation assay and MALDI-TOF mass spectrometry. STRING database was used to explore the functional relationship. Result Co-immunoprecipitation demonstrated lack of a direct interaction between RS1 and NDP and was further substantiated by mass spectrometry. However, STRING revealed a potential indirect functional association between the two proteins. Progressively, our analyses indicate that FZD4 protein interactome via PLIN2 as well as the MAP kinase signaling pathway to be a likely link bridging the functional relationship between retinoschisis and Norrie disease.
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.
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