DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cone-rod dystrophy 2 — screening already-approved drugs against its 3-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 2 maps to a 3-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 2 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
AIP like 1 HSP90 co-chaperone (AIPL1) — AIPL1 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 gerdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5U9J · 2.1 Å · ligand GERAN-8-YL GERAN (GER). Experimental structure, not a prediction.
What the evidence adds up to
In a 1993 prospective study of 33 patients from 25 families, cone-rod dystrophy was divided into two electroretinographic types: 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 further split into two subtypes based on visual field loss and threshold patterns. Among 95 of 150 additional retrospective patients with sufficient data, all but two fitted one of these four subtypes. The authors proposed these subtypes might aid counselling and genetic studies, but no molecular cause was identified.
Cone dystrophy with supernormal rod response (CDSRR) was studied in 17 patients from 13 families in 2008. All patients carried mutations in KCNV2, either homozygous or compound heterozygous; ten of eleven mutations were novel, including missense, truncating, and one gross deletion. No mutations were found in PDE6H. Visual acuity was reduced to a variable degree, colour vision was defective, and macular defects ranging from mild pigmentary changes to distinct foveal atrophy were present in nine patients. Progression was noted in only three of seven patients with follow-up. A 2005 case series of ten CDSRR patients reported symptom onset in the first or second decade, with reduced central vision, photophobia, myopia, and severely reduced red-green colour discrimination with relative preservation of tritan colour vision. Nyctalopia appeared later. Electrophysiology showed marked macular dysfunction, reduced and delayed cone responses, and supernormal and delayed rod responses. No disease-causing variants in NR2E3 were found.
A 1995 study of a four-generation family with autosomal dominant cone-rod dystrophy linked to chromosome 19q examined 34 affected and 22 unaffected members. Visual acuity loss began in the first decade, night blindness after age 20, and little function remained after age 50. Central and later peripheral fundus changes were accompanied by central scotoma, pseudoaltitudinal field defects, and eventual global loss. Before age 26, cone loss was more marked than rod loss. The authors noted the phenotype did not fit previous subtypes. Another 1995 report described a Japanese family with autosomal dominant cone-rod dystrophy and a negative electroretinogram. The proband, a 45-year-old man, had bull’s eye maculopathy and a negative bright-flash ERG; his father and one of three children also showed negative ERG responses, the child without fundus changes. No mutations were found in rhodopsin or peripherin/RDS.
A 1981 linkage study of five generations of a family with autosomal dominant cone-rod dystrophy with complete penetrance examined 73 members with 17 biochemical and serological markers. Twenty-five relatives were affected. No linkage was established by maximum likelihood analysis. What remains missing is a clear molecular diagnosis for most cone-rod dystrophy families, a trial design that accounts for the functional subtypes and variable progression described, and patient stratification by genotype and electrophysiological type before any intervention can be meaningfully tested.
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.
Cone Dystrophy with Supernormal Rod Response Is Strictly Associated with Mutations in<i>KCNV2</i>
AbstractPURPOSE: Cone dystrophy with supernormal rod response (CDSRR) is a retinal disorder characterized by reduced visual acuity, color vision defects, and specific alterations of ERG responses that feature elevated scotopic b-wave amplitudes at high luminance intensities. Mutations in PDE6H and in KCNV2 have been described in CDSRR. A combined clinical and genetic study was conducted in a cohort of patients with CDSRR, to substantiate these prior METHODS: Seventeen patients from 13 families underwent a detailed ophthalmic examination including color vision testing, Goldmann visual fields, fundus photography, Ganzfeld and multifocal ERGs, and optical coherence tomography. The coding sequences and flanking intron/UTR sequences of PDE6C and KCNV2 were screened for mutations by means of DHPLC and direct DNA sequencing of PCR-amplified genomic DNA. results. Whereas no mutations were detected in the PDE6H gene, mutations in KCNV2 were identified in all patients, in either the homozygous or compound heterozygous state. Ten of the 11 identified mutations were novel, including three missense and six truncating mutations and one gross deletion. The mutations concordantly segregate in all available families according a recessive mode of inheritance. The CDSRR phenotype was associated with reduced visual acuity of variable degree and color vision defects. Macular defects ranging from mild pigmentary changes to distinct foveal atrophy were present in nine patients. Progression of the disease was observed in only three of seven patients with follow-up data. CONCLUSIONS: The phenotype of cone dystrophy with supernormal rod response is tightly linked with mutations in KCNV2.
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.
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.
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.
Exogenously administered adenosine attenuates renal damage in streptozotocin-induced diabetic rats
AbstractBACKGROUND: Diabetic nephropathy (DNP) is one of the most serious complications of diabetes mellitus (DM). In the present study, we investigated the potential of adenosine as a therapeutic candidate for preventing DNP. METHODS: Twenty-one adult male rats were included in the study. Fourteen rats were administered a single dose of 60 mg/kg streptozotocin (STZ) to induce diabetes. Seven rats served as normal control group. Diabetic rats were randomly divided into two groups: one group was treated with 1 mL/kg saline/day (DM + saline) and the other group was treated with 5 mg/kg/day adenosine (DM + adenosine) for 6 weeks. After 6 weeks, biochemical parameters including urea, creatinine, blood urea nitrogen (BUN), kidney injury molecule-1 (KIM-1) and tumor necrosis factor-α (TNF-α) were measured in plasma samples. Also, kidneys were removed for histopathological assessment. RESULTS: Both of plasma KIM-1 and TNF-α levels were significantly higher in DM + saline group compared to controls. However, treatment of diabetic rats with adenosine significantly decreased the plasma KIM-1 and TNF-α levels compared to DM + saline group. Significant histopathological changes were observed in diabetic rats whereas adenosine treatment effectively prevented these changes. CONCLUSIONS: The findings of the present study suggest that adenosine may be a useful therapeutic agent for preventing DNP.
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.
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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