DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cone-rod dystrophy 24 — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCone-rod dystrophy 24 maps to a 1-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 cone-rod dystrophy 24 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
unc-119 lipid binding chaperone (UNC119) — UNC119 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 gnpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4GOJ · 2.1 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER (GNP). Experimental structure, not a prediction.
What the evidence adds up to
In 33 patients from 25 families, two major electroretinographic types of cone-rod dystrophy were identified: type 1, where cone amplitudes were reduced more than rod amplitudes, and type 2, where cone and rod amplitudes were reduced equally. Each type was subdivided by visual field loss patterns. Among 95 additional patients with sufficient data, all but two fit one of the four subtypes. A separate study of 10 patients with cone dystrophy and supernormal rod ERG found onset in the first or second decade, with reduced central vision, photophobia, myopia, and severely reduced red-green colour discrimination while tritan colour vision was relatively preserved. Nyctalopia appeared later. No disease-causing variants in NR2E3 were found in four tested patients.
Mutations in KCNV2 were identified in eight unrelated patients with cone dystrophy and supernormal rod ERG, with every patient carrying one or two mutations including frameshift, nonsense, non-stop, and missense changes. The authors concluded that KCNV2 mutations account for most if not all cases of this specific form. In a four-generation pedigree of autosomal dominant cone-rod dystrophy linked to chromosome 19q, 34 affected and 22 unaffected members were examined. Loss of visual acuity began in the first decade, night blindness after age 20, and little function remained after age 50. Psychophysical and electrophysiologic testing before age 26 showed more marked loss of cone than rod function. The phenotype did not fit well into previous subtypes.
No treatment or intervention was tested in any of these studies. What remains missing is any therapy for any genetic form of cone-rod dystrophy, along with the clinical trial infrastructure, patient stratification by genotype and functional subtype, and funding needed to develop and test potential treatments.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Ophthalmology · 1993 · 87 citations
Clinical Subtypes of Cone-Rod Dystrophy
AbstractOBJECTIVE: To determine possible distinct phenotypic subtypes of cone-rod dystrophy. PATIENTS: Thirty-three patients with cone-rod dystrophy (from 25 families) were assessed prospectively on electroretinography, visual field testing, psychophysical threshold profiles, and fundus features. The clinical records of an additional 150 patients with cone-rod dystrophy were examined retrospectively in terms of the classification schema derived from the prospective study. RESULTS: Based on electroretinographic recordings, two major types of cone-rod dystrophy were differentiated. In type 1, cone amplitudes were reduced to a greater degree than were rod amplitudes on electroretinography, while in type 2, cone and rod electroretinographic amplitudes were reduced in equal proportion. These two types were further subdivided on the basis of patterns of visual field loss and threshold elevation. In type 1a, there was a central or paracentral scotoma, and cone thresholds were more elevated centrally than peripherally. In type 1b, there was no central scotoma, and cone thresholds were more elevated peripherally than centrally. In type 2a, there was a central scotoma, cone thresholds were more elevated centrally than peripherally, and rod thresholds were more elevated peripherally than centrally. In type 2b, a partial or complete ring scotoma was present, cone thresholds were more elevated peripherally than centrally, and rod thresholds were more elevated in the midperipheral than in either the central or far peripheral region of the retina. Of the 150 additional patients with cone-rod dystrophy, data sufficient for classification were available for 95 patients, and all but two had findings that were consistent with classification into one of these four subtypes. CONCLUSION: Our results identify four functionally distinct subtypes of cone-rod dystrophy that may be useful for patient counseling and future molecular genetic studies.
British Journal of Ophthalmology · 2005 · 70 citations · open access
A detailed phenotypic study of "cone dystrophy with supernormal rod ERG"
AbstractAIMS: To characterise the detailed phenotype of "cone dystrophy with supernormal rod ERG" in a case series of 10 patients. METHODS: 10 affected patients were examined clinically and underwent colour fundus photography, with nine undergoing detailed electrophysiological testing. Five patients were assessed further with fundus autofluorescence (AF) imaging, automated photopic and dark adapted perimetry, and dark adaptometry. Detailed colour vision assessment was performed in six subjects. Blood samples were taken from four patients for DNA extraction and mutation screening of NR2E3 was undertaken. RESULTS: The onset of symptoms was in the first and second decades of life. Subjects presented with reduced central vision and marked photophobia. All individuals were myopic and colour vision testing revealed severely reduced colour discrimination predominantly along the red-green axes; tritan colour vision was relatively well preserved. Nyctalopia is a later feature of the disorder. Funduscopy and AF imaging revealed a range of macular appearances. There was electrophysiological evidence of marked macular dysfunction, reduced and delayed cone responses, and supernormal and delayed rod responses. Photopic and dark adapted perimetry revealed central scotomata with widespread peripheral sensitivity loss. No disease causing sequence variants in NR2E3 were identified. CONCLUSIONS: The largest case series to date has been described of the clinical, psychophysical and electrophysiological characteristics of this unusual cone dystrophy with supernormal rod responses. Electrophysiological data were consistent with a post-phototransduction, but pre-inner nuclear layer, site of dysfunction. While the definitive diagnosis can only be made with electrophysiological testing, several characteristics that may increase suspicion of this diagnosis are presented.
Novel Mutations in the<i>KCNV2</i>Gene in Patients with Cone Dystrophy and a Supernormal Rod Electroretinogram
AbstractPURPOSE: To identify mutations in KCNV2 in patients with a form of cone dystrophy characterized by a supernormal rod electroretinogram (ERG). METHODS: The 2 exons and flanking intron DNA of KCNV2 from 8 unrelated patients were PCR amplified and sequenced. RESULTS: We found 1 frameshift, 2 nonsense, 1 non-stop, and 6 missense mutations. Every patient had one or two mutations identified. Of the missense mutations, 4 affected residues were in the amino terminal region of the protein, and two in the pore region. CONCLUSIONS: KCNV2 mutations account for most if not all cases of cone dystrophy with a supernormal rod ERG.
AbstractOBJECTIVE: To describe the phenotype in a family with dominantly inherited cone-rod dystrophy with chromosome assignment to a 19q locus, and to correlate this with current classifications of this retinal dystrophy. DESIGN: A detailed clinical examination including Goldmann perimetry was undertaken in all family members. Six members under the age of 30 years underwent dark-adapted electroretinography, color contrast-sensitivity measurement, dark-adapted static perimetry, and dark adaptometry. PATIENTS: The study included 34 affected and 22 unaffected patients in four generations of a pedigree that manifested autosomal dominant cone-rod retinal dystrophy linked to a chromosome 19q locus by genetic linkage analysis. RESULTS: Loss of visual acuity occurred in the first decade of life, onset of night blindness occurred after 20 years of age, and little visual function remained after the age of 50 years. Central and, later, peripheral retinal fundus changes were associated with central scotoma, pseudoaltitudinal field defects, and finally global loss of function. Psychophysical and electrophysiologic testing before the age of 26 years showed more marked loss of cone than rod function. CONCLUSIONS: The phenotype associated with this mutation does not fit well into previous subtypes of cone-rod dystrophy. Further studies will be needed to correlate specific genetic mutations in this group of conditions with the various clinical phenotypes.
Klinische Monatsblätter für Augenheilkunde · 2008 · 8 citations
Intraepitheliale Phototherapeutische Keratektomie und Alkohol-Abrasio zur Therapie der rezidivierenden Erosio corneae - zwei minimalinvasive chirurgische Alternativen
AbstractBACKGROUND: Phototherapeutic keratectomy (PTK) has become established as a successful therapy for recurrent corneal erosions. After epithelial debridement, Bowman's lamella and anterior stroma are ablated by the Excimer laser. We have evaluated two alternative stroma-sparing treatment options, intraepithelial PTK, and alcohol delamination. PATIENTS AND METHODS: All treatments were performed in the relapse-free period. 17 eyes with recurrent corneal erosions were treated with intraepithelial PTK: from the intact epithelium, 12 - 25 microm of tissue were ablated by the Excimer laser (group I). Alcohol delamination was performed in 13 eyes (group II). Follow-up time was between 6 months and 7 years (mean 4.2 years). RESULTS: Both methods turned out to be safe, no refractive changes were detectable. After intraepithelial PTK, we saw a cumulative recurrence rate of 12 % after 1 year, 18 % after 2 years, and 24 % after 3 years, and a temporary subepithelial scaring was seen. Alcohol delamination resulted in a recurrence rate of 15 % during the whole follow-up time (no statistically significant difference compared to intraepithelial PTK), showing no haze or scarring. CONCLUSION: Both minimally invasive, stroma-sparing methods were effective for the treatment of trauma-associated recurrent erosion. The ablation of Bowman's lamella or anterior stroma does not seem to be necessary. However, for basal membrane dystrophy, we recommend PTK after epithelial debridement for the partial ablation of Bowman's lamella.
A novel homozygous missense variant in <i>POC1B</i> causes cone dystrophy in a consanguineous Pakistani family
AbstractBACKGROUND: Cone dystrophy is a heterogeneous hereditary retinal disorder with disease symptoms appearing in the late first or early second decades of life. METHODS: A consanguineous Pakistani family with three affected individuals underwent detailed clinical and genetic investigation. RESULTS: The proband, a 63-years old male, showed severely reduced day vision, a visual acuity of counting fingers (CF), color vision deficiency, high myopia and photophobia. Fundus images showed bilateral peripapillary atrophy, bilateral dull foveal reflex, tilted disc, tessellated fundus, and hyperfluorescence at the peripheral superior temporal arcade and leak at an early stage. OCT macula and angiography findings suggested traction near the disc in the right eye and sub-retinal fluid at the fovea in the left eye. Retinal layers were normal toward the periphery but disorganized near the disc. Full visual field tests showed bilateral central scotoma, while single visual field tests indicated bilateral generalized depression of the visual field. The proband showed normal bilateral intraocular pressure, normal choroidal vessels, and unremarkable anterior segment. Exome sequencing identified a novel homozygous missense variant (POC1B:NM_172240.3:c.1391T>C;p.L464P) in the proband. Existing evidence supported pathogenicity of the identified variant in the family. CONCLUSION: In conclusion, we document a first-ever Pakistani family with POC1B-related cone dystrophy.
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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