DeCure for Cone dystrophy with supernormal rod response
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cone dystrophy with supernormal rod response — 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 dystrophy with supernormal rod response 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 dystrophy with supernormal rod response 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 1993 prospective study of 33 patients with cone-rod dystrophy from 25 families, plus retrospective review of 150 additional patients, two major electroretinographic types were identified. Type 1 showed cone amplitudes reduced more than rod amplitudes; type 2 showed cone and rod amplitudes reduced in equal proportion. Each type was subdivided by visual field loss and threshold patterns, yielding four functional subtypes. Among 95 retrospectively reviewed patients with sufficient data, all but two fit one of these four subtypes.
A 1995 report described a Japanese family with autosomal dominant cone-rod dystrophy and a negative electroretinogram, a combination not previously reported. The proband, a 45-year-old man, had bull’s eye maculopathy and a negative bright-flash ERG. His father had macular degeneration and a negative ERG; one of the proband’s three children had a negative ERG without fundus changes. No mutations were found in the rhodopsin or peripherin/RDS genes.
A 2011 study followed three siblings homozygous for the p.G461R mutation in KCNV2 for up to 14 years, from ages 5 years, 4 years, and 2 months. All three developed nystagmus, increased light sensitivity, reduced colour discrimination, and relative central scotomas. Visual acuities ranged from 20/200 to 20/70. Scotopic sensitivity was reduced by 2 log units and photopic sensitivity by 1 log unit. ERG responses were markedly delayed; photopic amplitudes were severely reduced. Scotopic b-waves rose steeply with flash intensity, but supernormal amplitudes for the standard flash were reached only in the girl. No patient showed unequivocal signs of rod degeneration, though rod dysfunction was present.
A 2024 case report described a 56-year-old patient with a classical rod-cone dystrophy associated with a GNB1 mutation (c.217G>C, p.Ala73Pro), the second confirmed case linking this gene to rod-cone dystrophy. The patient also had mild intellectual disability, attention deficit/hyperactivity disorder, and truncal obesity. The authors recommend including GNB1 in genetic testing panels for inherited retinal diseases. What remains missing is a unified molecular classification that accounts for the phenotypic heterogeneity seen across these reports, and any prospective trial that tests whether stratification by genetic subtype or ERG pattern improves prediction of disease course. No therapy is tested or proposed in any of these abstracts.
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 · 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.
Long-Term Follow-Up of the Human Phenotype in Three Siblings with Cone Dystrophy Associated with a Homozygous<i>p.G461R</i>Mutation of<i>KCNV2</i>
AbstractPURPOSE: To provide an up to 14-year overview of the early ocular phenotype in siblings with a homozygous p.G461R mutation in the KCNV2 gene. METHODS: Two brothers and their sister were followed-up clinically from ages 5 years, 4 years, and 2 months, respectively, including complete ophthalmological examinations. Goldmann visual fields, two-color-threshold (2CT) perimetry, color vision testing, optical coherence tomography (OCT), fundus autofluorescence (FAF), and Ganzfeld electroretinograms (ERGs) were performed according to age-related capabilities. Genetic analyses included whole genome linkage analysis, homozygosity mapping, and candidate gene sequencing. RESULTS: All three siblings were homozygous for the p.G461R mutation. At 5 months, the younger brother had no nystagmus and Teller-acuity of 3.2 cyc/deg. At older age, all three presented nystagmus, increased light sensitivity, reduced color discrimination, and relative central scotomas. Visual acuities ranged from 20/200 to 20/70. The macula developed minor irregularities of the RPE, thinning in optical coherence tomography, and a ring of increased FAF. Scotopic (rod) sensitivity was reduced by 2 log and photopic sensitivity by 1 log in two-color-threshold perimetry. ERG responses were markedly delayed. Photopic amplitudes were severely reduced. Scotopic b-waves rose steeply with flash intensity, but for the standard flash supernormal amplitudes were only reached in the girl. CONCLUSIONS: FAF was similar to that in cone-rod dystrophy. Although cone dysfunction was accompanied by rod dysfunction, and scotopic ERGs in patient 2 deteriorated, no patient demonstrated any unequivocal sign of rod degeneration. Grossly delayed b-waves with a steep response-versus-intensity relationship rather than supernormal amplitudes should remind clinicians of this specific condition.
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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