DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Newfoundland cone-rod dystrophy — 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 moduleNewfoundland cone-rod dystrophy 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 newfoundland cone-rod dystrophy 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
retinaldehyde binding protein 1 (RLBP1) — RLBP1 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 retdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4CJ6 · 1.896 Å · ligand RETINAL (RET). Experimental structure, not a prediction.
What the evidence adds up to
In a prospective study of 33 patients from 25 families, cone-rod dystrophy was divided into two major electroretinographic types. Type 1 showed cone amplitudes reduced more than rod amplitudes; type 2 showed equal reduction of both. Each type was further split into two subtypes based on visual field loss and threshold patterns. Among 95 additional retrospective patients, all but two fit one of the four subtypes. The classification was proposed for counselling and molecular genetic studies, but no treatment or genetic cause was identified.
A case series of 10 patients with “cone dystrophy with supernormal rod ERG” reported 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. Electroretinography showed marked macular dysfunction, reduced and delayed cone responses, and supernormal and delayed rod responses. Perimetry revealed central scotomata with widespread peripheral sensitivity loss. No disease-causing variants in NR2E3 were found. The authors noted that definitive diagnosis requires electrophysiology, and the site of dysfunction appeared post-phototransduction but pre-inner nuclear layer.
A linkage study in a five-generation family with autosomal dominant cone-rod dystrophy and complete penetrance examined 73 family members, of whom 25 were affected. No linkage was found between the disease gene and 17 biochemical and serological markers.
A 2024 case report described a 56-year-old patient with classical rod-cone dystrophy carrying a GNB1 mutation (c.217G>C, p.Ala73Pro). The patient also had mild intellectual disability, attention deficit/hyperactivity disorder, and truncal obesity. This is the second reported case linking GNB1 to rod-cone dystrophy. The authors recommended including GNB1 in genetic testing panels for inherited retinal diseases.
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.
Pathological and Electrophysiological Features of a Canine Cone–Rod Dystrophy in the Miniature Longhaired Dachshund
AbstractPURPOSE: To characterize the electrophysiological and histopathological features of a retinal degenerative disease in a colony of miniature longhaired dachshunds known to have a form of progressive retinal atrophy (PRA). METHODS: Serial electroretinograms were recorded from affected homozygous (n = 36) and heterozygous (n = 15) dogs. Morphologic investigations including immunohistochemistry and lectin histochemistry were performed on selected homozygous animals (n = 15). RESULTS: Clinical findings included loss of tapetal hyperreflectivity. The mode of inheritance was autosomal recessive. An early dramatic reduction of cone-specific ERG amplitude with a more modest reduction in rod b-wave amplitude was demonstrated. Progressively, rod specific responses diminished until there were no recordable responses to the ERG stimuli at 40 weeks of age. Morphologic changes confirmed early cone inner and outer segment loss. Other abnormalities included opsin mislocalization and outer nuclear layer thinning due to the subsequent loss of rod photoreceptors. CONCLUSIONS: A novel canine cone-rod dystrophy has been identified.
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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