DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for X-linked retinoschisis — 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 moduleX-linked retinoschisis 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 x-linked 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
cyclin dependent kinase like 5 (CDKL5) — CDKL5 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-[(3-cyclopentyl-1h-pyrazol-5-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4BGQ · 2.0 Å · ligand [4-({4-[(3-cyclopentyl-1H-pyrazol-5-yl)amino]pyrimidin-2-yl}amino)phenyl]acetonitrile (38R). Experimental structure, not a prediction.
What the evidence adds up to
X-linked retinoschisis is a recessively inherited retinal degeneration caused by mutations in the RS1 gene. More than 80% of cases are due to missense mutations, though rare intragenic microdeletions have also been reported. A 2016 case report described a 17-year-old male with foveal and peripheral schisis and a Mizuo-Nakamura phenomenon, in whom sequencing revealed a novel in-frame deletion affecting the discoidin domain of retinoschisin. A 2006 report identified a novel Leu103Phe missense mutation in a Korean family. A 2014 study of a consanguineous family found a c.293C>A mutation in the RS1 gene across five affected individuals, including one homozygous female; the authors noted wide phenotypic variability, with the index patient showing a ring of enhanced autofluorescence and outer retinal atrophy, while his mother had a central atrophic retina with reduced autofluorescence signal.
Clinical diagnosis can be challenging because presentation varies widely and diagnostic tests may be normal at early stages. Electroretinography typically shows a reduced a/b ratio. A 2020 commentary co-authored by an adult patient and two ophthalmologists described the patient’s experience of sight loss and the diagnosis and management of the condition, but provided no new quantitative data on treatment outcomes.
A 2016 review stated that phase I clinical trials for X-linked retinoschisis had begun in the USA using adeno-associated virus (AAV8 or AAV2) mediated gene delivery. The review noted that three mouse models had been established and that new AAV vectors capable of transducing more retinal cells via intravitreal delivery were under development. No results from those trials were reported in the abstracts provided. What remains missing are published data from completed or ongoing human gene therapy trials, including any measures of visual function, safety, or durability of effect, as well as any validated patient stratification criteria that might predict which individuals respond to treatment.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Retina · 2014 · 12 citations
X-LINKED JUVENILE RETINOSCHISIS IN A CONSANGUINEOUS FAMILY
AbstractPURPOSE: To describe the phenotypic variability in a consanguineous family with genetically confirmed X-linked retinoschisis. METHODS: Five patients, including one homozygous female, were characterized by clinical examination, optical coherence tomography, fundus autofluorescence, mapping of macular pigment optical density, electroretinography, and DNA testing. RESULTS: The 36-year-old male index patient showed a ring of enhanced autofluorescence and outer retinal atrophy on optical coherence tomography. Electroretinography testing revealed a reduced a/b ratio. His mother presented with a central atrophic retina with markedly reduced autofluorescence signal and a surrounding ring of enhanced autofluorescence. The 40-year-old brother of the index patient and his 2 sons showed characteristic signs for X-linked retinoschisis, including retinal schisis and a reduced a/b ratio. Genetic testing revealed a c.293C>A mutation in the RS1 gene in all affected family members while the mother of the index patient was homozygous for this mutation. CONCLUSION: X-linked retinoschisis can present with a wide phenotypic variability. Here, detailed family history and genetic testing established the diagnosis of X-linked retinoschisis despite striking differences in phenotypic presentation in affected subjects, homozygosity of one affected female, and seemingly dominant inheritance in three subsequent generations because of multiple consanguinity.
BMC Medical Genetics · 2016 · 5 citations · open access
X-Linked retinoschisis associated to a novel intragenic microdeletion: case report
AbstractBACKGROUND: X-linked retinoschisis is a recessively inherited retinal degeneration. Clinical diagnosis can be challenging due to the highly variable phenotypic presentation. Also, clinical diagnostic tests may be normal at early stages of this condition. Therefore, genetic diagnosis has become a priceless tool in the management of this disease. CASE PRESENTATION: We present a case of a 17-year-old caucasian male with foveal and peripheral schisis, along with Mizuo-Nakamura phenomenon. RS1 sequencing led to the discovery of an in-frame deletion not previously described in the literature. CONCLUSIONS: Genetic deletions causative of X-linked retinoschisis are quite rare, since more than 80 % are caused by misssense mutations. In this particular case, its pathological effect comes from affecting a key element of the retinoschisin, the discoidin domain.
Korean Journal of Ophthalmology · 2006 · 3 citations · open access
A Novel Mutation in the XLRS1 Gene in a Korean Family with X-linked Retinoschisis
AbstractPURPOSE: To report a novel missense mutation in the XLRS1 gene in a Korean family with X-linked retinoschisis. METHODS: Observation case report of a family with a proband with X-linked retinoschisis underwent complete ophthalmologic examination. Genomic DNA was excluded from the family's blood and all exons of the XLRS1 gene were amplified by polymerase chain reaction and analyzed using a direct sequencing method. RESULTS: A novel Leu103Phe missense mutation was identified. CONCLUSIONS: A novel Leu103Phe mutation is an additional missense mutation which is responsible for the pathogenesis of X-linked retinoschisis.
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.
Molecular genetics and gene therapy of X-linked congenital retinoschisis
AbstractX-linked retinoschisis (XLRS) is a rare X-linked inherited retinal disorder, caused by mutations in retinoschisin 1 (RS1) gene. Three XLRS mice were established, providing ideal systems to study the mechanism and treatment methods for XLRS. RS1 gene mutations can induce abnormal secretion or adhesion function of RS1 protein. In the past year, phase I clinical trials for XLRS has begun in USA, using adeno associated virus (AAV, AAV8 or AAV2)-mediated gene delivery. With the rapid development of new generation of AAV vector that can transduce more retinal cells through intravitreous delivery, gene therapy for XLRS will have a brighter future.
Key words:
Retinoschisis/genetics; Gene Therapy; Review
Güncel Retina Dergisi (Current Retina Journal) · 2021 · 0 citations · open access
X-linked Retinoschisis
AbstractX-linked retinoschisis (XLRS) is a degenerative retinal disease, often affecting men, characterized by progressive dissociation in the inner layers of the retina with negative electroretinography (ERG). In this review, the clinical presentation of the disease, diagnostic tests, the pathophysiology of the disease, treatment options to date, and possible treatment alternatives in the future are aimed to be examined.
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.
