DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for X-linked cone-rod dystrophy 1 — 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 moduleX-linked cone-rod dystrophy 1 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 x-linked cone-rod dystrophy 1 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
retinitis pigmentosa GTPase regulator (RPGR) — RPGR 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4JHN · 1.7 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 1993 study of 33 patients with cone-rod dystrophy from 25 families, plus retrospective records of 150 additional patients, identified four functional subtypes based on electroretinography and visual field patterns. Type 1 showed cone amplitudes reduced more than rod amplitudes; type 2 had equal reduction of both. Each type was subdivided by scotoma location and threshold profiles. Of 95 retrospective 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 configuration not previously reported in this inheritance pattern. The proband, a 45-year-old man, had bull’s eye maculopathy; his father had macular degeneration, and one of the proband’s three children had the negative ERG without fundus changes. No mutations were found in the rhodopsin or peripherin/RDS genes.
A 2005 case series of 10 patients with “cone dystrophy with supernormal rod ERG” found symptom onset in the first or second decade, with reduced central vision, photophobia, myopia in all, and severely reduced colour discrimination along red-green axes while tritan vision was relatively preserved. Nyctalopia appeared later. Electrophysiology 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 identified. The authors concluded the dysfunction site is post-phototransduction but pre-inner nuclear layer.
A 2016 Danish study of Åland eye disease (AED) / incomplete congenital stationary night blindness identified 74 individuals from 35 families over 34 years, with an estimated birth prevalence of 1 per 22,000 live-born males. Of 60 subjects from 29 families who participated in follow-up, 59 had a CACNA1F mutation and one had a CABP4 mutation. Among those with CACNA1F mutations, all had subnormal visual acuity, 63% had nystagmus, foveal hypoplasia was present in 25 of 43 subjects, and outer segment length at the fovea was significantly reduced. The authors argue that AED, iCSNB, and X-linked cone-rod dystrophy 3 are a continuous spectrum caused mostly by CACNA1F mutations.
Two abstracts on Duchenne muscular dystrophy and dystrophinopathies are included but describe a different X-linked disease with no relevance to cone-rod dystrophy. For X-linked cone-rod dystrophy 1 specifically, no abstracts in this set report any drug treatment, clinical trial, or therapeutic intervention. What is missing is any funded trial of a candidate drug, a defined patient stratification system that maps the known functional subtypes to genetic or molecular targets, and the investment needed to move from phenotypic description to interventional study.
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.
Frontiers in Medicine · 2022 · 40 citations · open access
Therapeutic Strategies for Dystrophin Replacement in Duchenne Muscular Dystrophy
AbstractDuchenne muscular dystrophy (DMD) is an X-linked hereditary disease characterized by progressive muscle wasting due to modifications in the DMD gene (exon deletions, nonsense mutations, intra-exonic insertions or deletions, exon duplications, splice site defects, and deep intronic mutations) that result in a lack of functional dystrophin expression. Many therapeutic approaches have so far been attempted to induce dystrophin expression and improve the patient phenotype. In this manuscript, we describe the relevant updates for some therapeutic strategies for DMD aiming to restore dystrophin expression. We also present and analyze in vitro and in vivo ongoing experimental approaches to treat the disease.
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.
CONTINUUM Lifelong Learning in Neurology · 2022 · 6 citations
The Dystrophinopathies
AbstractPURPOSE OF REVIEW: This article reviews the history, epidemiology, genetics, clinical presentation, multidisciplinary management, and established and emerging therapies for the dystrophinopathies. RECENT FINDINGS: The multidisciplinary care of individuals with dystrophinopathies continues to improve in many ways, including early surveillance and implementation of respiratory, cardiac, and orthopedic health management. The era of genetic therapeutics has altered the treatment landscape in neuromuscular disorders, including the dystrophinopathies. SUMMARY: The dystrophinopathies are a spectrum of X-linked genetic disorders characterized by childhood-onset progressive weakness and variable cardiac and cognitive involvement. Corticosteroids are the mainstay of therapy to slow disease progression. Additional strategies for disease amelioration and dystrophin restoration, including gene replacement therapy, are under investigation.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
