DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Leber congenital amaurosis — screening already-approved drugs against its 37-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLeber congenital amaurosis maps to a 37-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 leber congenital amaurosis 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
MER proto-oncogene, tyrosine kinase (MERTK) — MERTK 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 1~{s},2~{s}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7AAZ · 1.855 Å · ligand 2-azanyl-~{N}-[(1~{S},2~{S})-2-[[4-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]phenyl]methoxy]cyclopentyl]-5-(1-methylpyrazol-4-yl)pyridine-3-carboxamide (R6K). Experimental structure, not a prediction.
What the evidence adds up to
In a study of 100 consecutive Leber congenital amaurosis patients, mutations were identified in only 11% of cases. GUCY2D mutations accounted for 6%, RPE65 for 3%, and CRX for 2%. Visual evolution in patients with GUCY2D and CRX mutations remained stable, while individuals with RPE65 mutations showed progressive visual loss. The authors concluded that molecular diagnosis could provide information about prognosis and course of treatment.
A later report on CRB1-related LCA noted that 9-15% of LCA cases have mutations in the CRB1 gene. Three novel pathogenic variants were identified using whole exome sequencing and targeted gene panels, with validation by Sanger sequencing. The authors stated that next-generation sequencing techniques are efficient for identifying causative variants in disorders with locus heterogeneity.
A single case report of a girl with RPE65-confirmed LCA followed from age 4 to 11 described nyctalopia, myopia, and choroid ocular fundus. Electroretinogram was not measurable in all phases. The report noted that gene therapy for RPE65 LCA had been researched with good functional outcomes up to that point, but provided no numerical data on visual improvement, sample size beyond one patient, or long-term follow-up results.
What is still missing: large-scale, long-term natural history studies with quantitative visual function endpoints; prospective trials that stratify patients by specific gene mutation; and funding for trials that test therapies beyond the single RPE65 gene therapy approach, given that most LCA patients have mutations in other genes.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Ophthalmic Genetics · 2000 · 111 citations
Mutational analysis and clinical correlation in Leber congenital amaurosis
AbstractUNLABELLED: Leber congenital amaurosis (LCA, MIM 204001) is a clinically and genetically heterogeneous retinal disorder characterized by severe visual loss from birth, nystagmus, poor pupillary reflexes, retinal pigmentary or atrophic changes, and a markedly diminished electroretinogram (ERG). PURPOSE: To examine 100 consecutive patients with LCA in order to assess the relative burden of the three known genes involved in LCA, namely retinal guanylyl cyclase (GUCY2D), retinal pigment epithelium protein ( RPE65), and the cone-rod homeobox (CRX), and to define their clinical correlates. METHODS: Mutational analysis and detailed clinical examinations were performed in patients diagnosed with LCA at the Johns Hopkins Center for Hereditary Eye Diseases and the Montreal Children's Hospital. RESULTS: Mutations were identified in 11% of our patients: GUCY2D mutations accounted for 6%, while RPE65 and CRX gene mutations accounted for 3% and 2%, respectively. The clinical presentation was variable; however, the visual evolution in patients with mutations in GUCY2D and CRX remained stable, while individuals with mutations in the RPE65 gene showed progressive visual loss. CONCLUSIONS: This study suggests that molecular diagnosis of Leber congenital amaurosis could provide important information concerning prognosis and course of treatment.
CRB1-Related Leber Congenital Amaurosis: Reporting Novel Pathogenic Variants and a Brief Review on Mutations Spectrum
AbstractBackground: Leber congenital amaurosis (LCA) is a rare inherited retinal disease causing severe visual impairment in infancy. It has been reported that 9-15% of LCA cases have mutations in CRB1 gene. The complex of CRB1 protein with other associated proteins affects the determination of cell polarity, orientation, and morphogenesis of photoreceptors. Here, we report three novel pathogenic variants in CRB1 gene and then briefly review the types, prevalence, and correlation of reported mutations in CRB1 gene. Methods: Whole exome sequencing and targeted gene panel were employed. Then validation in the patient and segregation analysis in affected and unaffected members was performed. Results: Our detected novel pathogenic variants (p.Glu703*, c.2128+1G>A and p.Ser758SerfsX33) in CRB1 gene were validated by Sanger sequencing. Segregation analysis confirmed the inheritance pattern of the pathogenic variants. Conclusion: Our findings show that emerging the next-generation sequencing-based techniques is very efficient in identifying causative variants in disorders with locus heterogeneity.
Gaceta Médica de México · 2017 · 1 citations · open access
Amaurosis congénita de Leber RPE-65, seguimiento a 7 años
AbstractLeber congenital amaurosis is a retinal dystrophy with several forms of presentation due to its genetic variability. Case of a female girl followed up from 4 to 11 years old is presented, with positive clinical data of nyctalopia, myopia and choroid ocular fundus. Electroretinogram was not measurable in all phases but diagnostic was confirmed by RPE65 mutation genetic study. RPE65 Leber congenital amaurosis is particularly important as it has been researched for a gene therapy treatment with good functional outcomes up to now, awaiting to offer hope and a better quality of life to people with this 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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