DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Leber congenital amaurosis 9 — 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 moduleLeber congenital amaurosis 9 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 leber congenital amaurosis 9 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.
What the evidence adds up to
In a mouse model of guanylate cyclase-1 deficiency, which corresponds to LCA1 rather than LCA9, subretinal delivery of AAV vectors carrying murine GC1 cDNA restored cone function as measured by electroretinography. Responses were clearly measurable out to one year after treatment with the AAV8(Y733F) capsid mutant, which was the most efficient of the vectors tested. Cones were preserved for at least 11 months after treatment, and vector genomes were recovered primarily from the optic nerve of the treated eye, with only one brain sample positive out of 20. The authors state this is the first demonstration of long-term therapy lasting roughly one year in a mammalian model of GC1 deficiency, and they argue it justifies developing an AAV-based gene therapy vector for LCA1.
No abstract in this set addresses LCA9 specifically. One abstract reports three novel pathogenic variants in the CRB1 gene, which is associated with 9–15% of LCA cases, but CRB1-related LCA is a different genetic subtype. That study used whole exome sequencing and targeted gene panels to identify the variants and confirmed segregation by Sanger sequencing, noting that next-generation sequencing is efficient for identifying causative variants in disorders with genetic heterogeneity. A third abstract is a case report of three siblings with Leber congenital amaurosis in Kaduna State, Nigeria, describing it as an irreversible blinding condition; it discusses genetic issues, clinical presentation, counselling, and treatment but provides no quantitative outcome data.
For LCA9 specifically, no preclinical or clinical treatment data are available in these abstracts. What is missing is any gene therapy construct or animal model for the LCA9 gene, any clinical trial, and any patient stratification by the specific genetic mutation. Funding and trial design for LCA9 remain absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Long-term Preservation of Cone Photoreceptors and Restoration of Cone Function by Gene Therapy in the Guanylate Cyclase-1 Knockout (GC1KO) Mouse
AbstractPURPOSE: The authors previously showed that subretinal delivery of AAV5 vectors containing murine guanylate cyclase-1 (GC1) cDNA driven by either photoreceptor-specific (hGRK1) or ubiquitous (smCBA) promoters was capable of restoring cone-mediated function and visual behavior and preserving cone photoreceptors in the GC1 knockout (GC1KO) mouse for 3 months. Here, the authors compared therapy conferred by the aforementioned vectors to that achieved with the highly efficient capsid tyrosine mutant AAV8(Y733F) and asked whether long-term therapy is achievable in this model. METHODS: AAV5-hGRK1-mGC1, AAV5-smCBA-mGC1, or AAV8(Y733F)-hGRK1-mGC1 was delivered subretinally to GC1KO mice between postnatal day (P)14 and P25. Retinal function was assayed by electroretinography. Localization of AAV-mediated GC1 expression and cone survival were assayed with immunohistochemistry, and the spread of vector genomes beyond the retina was quantified by PCR of optic nerve and brain tissue. RESULTS: Cone function was restored with all vectors tested, with AAV8(Y733F) being the most efficient. Electroretinographic responses were clearly measurable out to 1 year after treatment. AAV-mediated expression of GC1 was found exclusively in photoreceptors out to 15 months after injection. Cones were preserved for at least 11 months after treatment. AAV5- and AAV8(733)-delivered vector genomes were recovered primarily from optic nerve of the treated eye and, in only instance, from brain (1 of 20 samples). CONCLUSIONS: The authors demonstrate for the first time that long-term therapy (∼1 year) is achievable in a mammalian model of GC1 deficiency. These data provide additional justification for the development of an AAV-based gene therapy vector for the clinical treatment of Leber congenital amaurosis-1.
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.
Nigerian Journal of Ophthalmology · 2008 · 1 citations · open access
Lebers Amaurosis in Three Siblings: A case report
AbstractThis case report appears to be first reported incident of Lebers congenital amaurosis in three siblings in Kaduna State. Genetic issues, clinical presentation, counselling, treatment and future progression of this irreversible blinding condition are discussed. Keywords: Lebers amaurosis, retinitis pigmentosa, Kaduna, NigeriaNigerian Journal of Ophthalmology Vol. 16 (1) 2008: pp. 26-29
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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