DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Usher syndrome type 1C — 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 moduleUsher syndrome type 1C 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 usher syndrome type 1c 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
USH1 protein network component harmonin (USH1C) — USH1C 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 mltdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5XBF · 1.802 Å · ligand D-MALATE (MLT). Experimental structure, not a prediction.
What the evidence adds up to
Seventy patients with Usher's syndrome were examined in 1983, and two distinct clinical types were distinguished based on differences in hearing impairment, vestibular sensitivity, and deterioration in retinal photoreceptor function. The classic description of Usher syndrome combines hearing loss with rod-cone dystrophy, and vestibular dysfunction is present in many patients. Three distinct clinical subtypes were documented in the late 1970s. Recent literature has described "atypical" Usher syndrome presentations, noting a wide discrepancy in the spectrum of phenotypic deviations from the classical presentation. No drug or treatment is mentioned in any of these abstracts.
In a 2013 study of 18 subjects from nine families with Usher syndrome type IIA, three different USH2A mutations were identified. Both similarities and differences of the auditory phenotype were seen within families with several affected siblings. A variable degree of hearing loss, ranging from mild to profound, was observed among affected subjects. No significant differences in hearing thresholds were found between groups of affected subjects with different pathological mutations. The authors concluded that mutations in the USH2A gene and the resulting phenotype are probably modulated by other variables such as modifying genes, epigenetics, or environmental factors.
A 2018 study of a Chinese family with three siblings diagnosed with Usher syndrome type IIC identified two novel compound heterozygous mutations in ADGRV1. The proband had typical fundus features supporting a diagnosis of retinitis pigmentosa. Audiometric testing indicated moderate to severe sensorineural hearing impairment while vestibular function was normal. The mutations co-segregated with the disease phenotype in the family. The authors stated the findings broaden the mutation spectrum of ADGRV1 and provide assistance for future genetic diagnosis and treatment.
No clinical trial data, no drug repurposing evidence, and no treatment outcomes are reported in these abstracts. What is still missing is any trial testing a drug in Usher syndrome type 1C specifically, any funding for such a trial, and any patient stratification strategy that accounts for the variable expressivity and modifying factors described in the literature.
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 · 1983 · 148 citations
Usher's Syndrome
AbstractThe conditions of 70 patients with Usher's syndrome were studied by ophthalmic and neuro-otologic examinations. Two distinct clinical and presumed genetic types were discernible on the basis of differences in hearing impairment, vestibular sensitivity, and, to a lesser extent, deterioration in retinal photoreceptor function. Distinguishing these two types has relevance for both diagnosis and genetic counseling of patients with Usher's syndrome.
Ophthalmic Genetics · 2020 · 35 citations · open access
Atypical and ultra-rare Usher syndrome: a review
AbstractUsher syndrome has classically been described as a combination of hearing loss and rod-cone dystrophy; vestibular dysfunction is present in many patients. Three distinct clinical subtypes were documented in the late 1970s. Genotyping efforts have led to the identification of several genes associated with the disease. Recent literature has seen multiple publications referring to "atypical" Usher syndrome presentations. This manuscript reviews the molecular etiology of Usher syndrome, highlighting rare presentations and molecular causes. Reports of "atypical" disease are summarized noting the wide discrepancy in the spectrum of phenotypic deviations from the classical presentation. Guidelines for establishing a clear nomenclature system are suggested.
International Journal of Audiology · 2013 · 29 citations
Expressivity of hearing loss in cases with Usher syndrome type IIA
AbstractOBJECTIVE: The purpose of this study was to compare the genotype/phenotype relationship between siblings with identical USH2A pathologic mutations and the consequent audiologic phenotypes, in particular degree of hearing loss (HL). Decade audiograms were also compared among two groups of affected subjects with different mutations of USH2A. DESIGN: DNA samples from patients with Usher syndrome type II were analysed. The audiological features of patients and affected siblings with USH2A mutations were also examined to identify genotype-phenotype correlations. STUDY SAMPLE: Genetic and audiometric examinations were performed in 18 subjects from nine families with Usher syndrome type IIA. RESULTS: Three different USH2A mutations were identified in the affected subjects. Both similarities and differences of the auditory phenotype were seen in families with several affected siblings. A variable degree of hearing loss, ranging from mild to profound, was observed among affected subjects. No significant differences in hearing thresholds were found the group of affected subjects with different pathological mutations. CONCLUSIONS: Our results indicate that mutations in the USH2A gene and the resulting phenotype are probably modulated by other variables, such as modifying genes, epigenetics or environmental factors which may be of importance for better understanding the etiology of Usher syndrome.
Identification of two novel compound heterozygous mutations of <i>ADGRV1</i> in a Chinese family with Usher syndrome type IIC
AbstractBACKGROUND: To describe the clinical and genetic findings in a Chinese family with three sibs diagnosed with Usher syndrome type IIC. MATERIALS AND METHODS: Four members received ophthalmic and otologic tests to ascertain the clinical characteristics. According to the clinical phenotype, we focused attention on a total of 658 genes associated with them. We screened the possible pathogenic mutation sites, used Sanger to exclude the false positive and verified whether there were co-segregated among the family members. RESULTS: Typical fundus features found in the proband supported the diagnosis of retinitis pigmentosa (RP). Audiometric test indicated moderate to severe sensorineural hearing impairment while the vestibular function was normal. Whole-exome sequencing identified the presence of two novel compound heterozygous mutations in ADGRV1, a known gene responsible for Usher syndrome type IIC. Mutationc.15008delG/p.Gly5003AlafsTer13 was inherited from the mother while c.18383_18386dupACAG/p.His6130GlnfsTer84 was inherited from the father, and they were co-segregated with the disease phenotype in the family. CONCLUSIONS: The mutations found in our study not only broaden the mutation spectrum of ADGRV1, but also provide assistances for future genetic diagnosis and treatment for Usher syndrome patients.
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.
