DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cone-rod dystrophy 3 — 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 moduleCone-rod dystrophy 3 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 cone-rod dystrophy 3 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
ATP binding cassette subfamily A member 4 (ABCA4) — ABCA4 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…
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RCSB Protein Data Bank · entry 7M1Q · 2.92 Å · ligand [(2S)-3-[2-[(E)-[(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenylidene]amino]ethoxy-oxidanyl-phosphoryl]oxy-2-[(Z)-octadec-9-enoyl]oxy-propyl] (Z)-octadec-9-enoate (HZL). Experimental structure, not a prediction.
What the evidence adds up to
Cone-rod dystrophy 3 is one of several clinical labels that, according to a 2016 Danish study, refer to a broad continuous spectrum of appearances caused mostly by mutations in CACNA1F. That study examined 74 individuals diagnosed with Åland eye disease over 34 years and found that 59 of 60 subjects in a follow-up cohort harboured a CACNA1F mutation, while one had a CABP4 mutation. Subnormal visual acuity was present in all subjects with a CACNA1F mutation, nystagmus in 63%, and foveal hypoplasia in 25 of 43 subjects. Foveal pit volume and outer segment length at the fovea were both significantly reduced compared to normal. The estimated birth prevalence was 1 per 22,000 live-born males. The authors argued that Åland eye disease, incomplete congenital stationary night blindness, and X-linked cone-rod dystrophy 3 are the same entity.
A 2007 study of eight unrelated patients with cone dystrophy and a supernormal rod electroretinogram found mutations in KCNV2 in every patient, including frameshift, nonsense, non-stop, and missense changes. That paper concluded that KCNV2 mutations account for most if not all cases of that specific electrophysiological phenotype. A 1993 prospective study of 33 patients from 25 families, plus retrospective review of 150 additional patients, proposed four functional subtypes of cone-rod dystrophy based on electroretinography and visual field patterns: type 1a, 1b, 2a, and 2b. Of the 95 retrospective patients with sufficient data, all but two could be classified into one of those four subtypes.
A 1995 report described a Japanese family with autosomal dominant cone-rod dystrophy and a negative electroretinogram, a configuration not previously reported in that inheritance pattern. The proband had bull’s eye maculopathy, his father had macular degeneration, and one of the proband’s three children showed no fundus changes but had the negative ERG. No mutations were found in the rhodopsin or peripherin/RDS genes. An earlier 1981 linkage study of a five-generation family with autosomal dominant cone-rod dystrophy with complete penetrance examined 17 biochemical and serological markers in 73 family members, of whom 25 were affected, but could not establish linkage to any of those markers. A 2024 case report described the second confirmed case of rod-cone dystrophy associated with a GNB1 mutation, in a 56-year-old patient who also had mild intellectual disability, attention deficit/hyperactivity disorder, and truncal obesity.
What is still missing: large-scale natural history studies that stratify patients by the specific gene (CACNA1F, KCNV2, GNB1, or unknown) and by the functional subtypes described in 1993; funding for clinical trials of any intervention in any of these genetically defined groups; and a trial design that accounts for the slow progression and variable expressivity of the disease.
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.
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.
Clinical Characteristics, Mutation Spectrum, and Prevalence of Åland Eye Disease/Incomplete Congenital Stationary Night Blindness in Denmark
AbstractPurpose: To assess clinical characteristics, foveal structure, mutation spectrum, and prevalence rate of Åland eye disease (AED)/incomplete congenital stationary night blindness (iCSNB). Methods: A retrospective survey included individuals diagnosed with AED at a national low-vision center from 1980 to 2014. A subset of affected males underwent ophthalmologic examinations including psychophysical tests, full-field electroretinography, and spectral-domain optical coherence tomography. Results: Over the 34-year period, 74 individuals from 35 families were diagnosed with AED. Sixty individuals from 29 families participated in a follow-up study of whom 59 harbored a CACNA1F mutation and 1 harbored a CABP4 mutation. Among the subjects with a CACNA1F mutation, subnormal visual acuity was present in all, nystagmus was present in 63%, and foveal hypoplasia was observed in 25/43 subjects. Foveal pit volume was significantly reduced as compared to normal (P < 0.0001). Additionally, outer segment length at the fovea was measured in 46 subjects and found to be significantly reduced as compared to normal (P < 0.001). Twenty-nine CACNA1F variations were detected among 34 families in the total cohort, and a novel CABP4 variation was identified in one family. The estimated mean birth prevalence rate was 1 per 22,000 live-born males. Conclusions: Our data support the viewpoint that AED, iCSNB, and X-linked cone-rod dystrophy 3 are designations that refer to a broad, continuous spectrum of clinical appearances caused in the majority by a variety of mutations in CACNA1F. We argue that the original designation AED should be used for this entity.
British Journal of Ophthalmology · 1995 · 18 citations · open access
Autosomal dominant cone-rod dystrophy with negative electroretinogram.
AbstractAIMS: The negative electroretinogram (ERG) is observed in many hereditary retinal disorders. However, no reports have described a negative ERG in a family with autosomal dominant cone-rod dystrophy. A Japanese family with autosomal dominant cone-rod dystrophy with negative ERG is described. METHOD: Members of a Japanese family with autosomal dominant cone-rod dystrophy were examined and evaluated with Goldmann and Humphrey perimetry, bright flash ERG with an intense white stimulus, rod, cone, and flicker ERGs, and fluorescein angiography. Molecular analysis of the rhodopsin and peripherin/RDS genes in the patients was also performed. RESULTS: A 45-year-old Japanese man (proband) presented with decreased visual acuity. His fundi revealed bull's eye maculopathy and his single flash bright ERG showed a negative configuration. Negative ERG responses also were found in his father, who had macular degeneration, and one of the proband's three children who showed no fundus changes. No irregularities were found in their rhodopsin or peripherin/RDS genes. CONCLUSION: The condition of this family is believed to represent a previously undescribed autosomal dominant cone-rod dystrophy.
American Journal of Medical Genetics · 1981 · 4 citations
Autosomal dominant cone‐rod dystrophy: A linkage study with 17 biochemical and serological markers
AbstractFive generations of a family with autosomal-dominant cone-rod dystrophy (CRD) with complete penetrance have been previously studied extensively clinically. The young members of this family were reevaluated, and blood from 73 available family members was studied with 17 biochemical and serological markers. A total of 25 relatives was found to be affected. Linkage between the gene for CRD in this family and the markers studied could not be established by maximum likelihood analysis.
Case Reports in Ophthalmology · 2024 · 1 citations · open access
GNB1-Related Rod-Cone Dystrophy: A Case Report
Abstract<b><i>Introduction:</i></b> The <i>GNB1</i> (guanine nucleotide-binding protein, β1) gene encodes for the ubiquitous β1 subunit of heterotrimeric G proteins, which are associated with G-protein-coupled receptors (GPCRs). <i>GNB1</i> mutations cause a neurodevelopmental disorder characterized by a broad clinical spectrum. A novel variant has recently been confirmed in a case of rod-cone dystrophy. <b><i>Case Presentation:</i></b> We describe the second confirmed case of a classical rod-cone dystrophy associated with a mutation located in exon 6 of <i>GNB1</i> [NM_002074.5:c.217G&gt;C, p.(Ala73Pro)] in a 56-year-old patient also presenting mild intellectual disability, attention deficit/hyperactivity disorder, and truncal obesity. <b><i>Conclusion:</i></b> This paper confirms the role of <i>GNB1</i> in the pathogenesis of a classic rod-cone dystrophy and highlights the importance of including this gene in the genetic analysis panel for inherited retinal diseases.
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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