DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Usher syndrome type 2 — screening already-approved drugs against its 5-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 2 maps to a 5-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 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
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
Usher syndrome type 2 is one of two distinct clinical and presumed genetic types discernible from a 1983 study of 70 patients, based on differences in hearing impairment, vestibular sensitivity, and deterioration in retinal photoreceptor function. A 1994 paper notes that the Usher Syndrome Consortium adopted clinical criteria for diagnosing type I and type II, used in subsequent consortium studies. A 2014 cross-sectional study of 433 patients (297 unrelated families) reported that comparison between type I and type II patients yielded P < .001 for most analysed items, including age at diagnosis, age at onset of night blindness, visual field loss, visual acuity loss, cataracts, and severity and age at diagnosis of hearing loss. The same study found that the two most frequent mutations in the USH2A gene were p.Glu767Serfs*21 (allelic frequency 23.2%, 63 of 272 alleles) and p.Cys759Phe (8.1%, 22 of 272 alleles). None of the patients carrying p.Cys759Phe exhibited severe hearing loss, and more than 60% had only mild hearing loss; most patients carrying p.Glu767Serfs*21 (72.1%) were moderately deaf.
A 2020 study of a family with Usher syndrome type I identified compound heterozygous variants in the MYO7A gene (c.2694+2T>G and c.6028G>A) in a proband who developed night blindness at age 10, bilateral cataract, retinal degeneration, and progressive hearing loss. Her sister carried the same variants with similar clinical phenotypes; a heterozygous daughter was phenotypically normal. A 2023 review describes Usher syndrome as a rare heterogeneous autosomal recessive genetic disorder with retinitis pigmentosa and hearing loss, estimated to occur in three per 100,000 individuals.
No drug treatment is mentioned in any of these abstracts. The 2014 paper states that detailed genotype-phenotype correlations allow an estimated prognosis and can improve clinical management, genetic counselling, and risk assessment, but it does not report any therapeutic intervention. What remains missing for any potential repurposing effort is evidence from controlled trials, funding for such trials, and a clear stratification of patients by genotype — particularly the USH2A mutations p.Glu767Serfs*21 and p.Cys759Phe — since hearing loss severity differs markedly between them.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Medical Genetics · 1994 · 344 citations
Clinical diagnosis of the Usher syndromes
AbstractThe Usher syndromes are genetically distinct disorders which share specific phenotypic characteristics. This paper describes a set of clinical criteria recommended for the diagnosis of Usher syndrome type I and Usher syndrome type II. These criteria have been adopted by the Usher Syndrome Consortium and are used in studies reported by members of this Consortium.
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.
JAMA Ophthalmology · 2014 · 76 citations · open access
Clinical Aspects of Usher Syndrome and the<i>USH2A</i>Gene in a Cohort of 433 Patients
AbstractIMPORTANCE: A new statistical approach is needed to describe the clinical differences between type I and type II Usher syndrome and between the 2 most frequent mutations in the USH2A gene. OBJECTIVES: To describe the primary phenotypic characteristics and differences between type I and type II Usher syndrome and to establish a phenotype-genotype correlation for the 2 most frequent mutations in the USH2A gene. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study at a genetics department, in which clinical evaluations were performed for 433 patients (297 unrelated families) who were classified as having type I, II, III, atypical, or unclassified Usher syndrome according to their clinical history, pedigree data, results from ophthalmological studies, and audiological, neurophysiological, and vestibular test results. Molecular studies were performed for 304 patients (256 unrelated families). The Mann-Whitney U test or the χ2 test was used for calculating the differences between mean values for the analyzed parameters. MAIN OUTCOMES AND MEASURES: Age at diagnosis; age at onset of night blindness, visual field loss, visual acuity loss, and cataracts; and severity and age at diagnosis of hearing loss. RESULTS: The comparison between patients with type I Usher syndrome and those with type II Usher syndrome revealed P < .001 for most items analyzed. The most frequent mutations in the USH2A gene were the p.Glu767Serfs*21 and p.Cys759Phe mutations, with an allelic frequency of 23.2% (63 of 272 alleles) and 8.1% (22 of 272 alleles), respectively. The phenotypic analysis for patients carrying p.Cys759Phe showed P < .001 for most items analyzed when compared with patients carrying p.Glu767Serfs*21 and when compared with patients carrying other mutations in the USH2A gene. None of the p.Cys759Phe patients exhibited a severe hearing loss phenotype, and more than 60% had only mild hearing loss. Most patients carrying the p.Glu767Serfs*21 mutation (72.1%) were moderately deaf. CONCLUSIONS AND RELEVANCE: Our study presents the clinical differences between type I and type II Usher syndrome and between the 2 most frequent mutations in the USH2A gene. Detailed genotype-phenotype correlations, as presented in our study, allow for a better correlation of clinical signs with a known genotype and can improve the clinical management, genetic counseling, and risk assessment of patients with Usher syndrome because an estimated prognosis of their disease can be made.
Eastern Mediterranean Health Journal · 2003 · 20 citations · open access
Psychosis in a patient with Usher syndrome: a case report
AbstractThe present report is the case of a 26-year-old man, born with Usher syndrome. The patient had had a significant hearing impairment since birth and had developed retinitis pigmentosa. He had originally been diagnosed with a depressive disorder and treated with antidepressants, with no subsequent improvement in his mental state. Following a deterioration in his mental state he was admitted for reassessment at the Queen Elizabeth Psychiatric Hospital, Birmingham, and antidepressants were stopped. It subsequently became apparent from observations, interviews with the patient and information from the patient's carers and relatives that he had a psychotic illness. Treatment was started with the antipsychotic drug risperidone, after which he showed significant improvement. The association between Usher syndrome and psychosis is discussed.
Ophthalmic Paediatrics and Genetics · 1991 · 4 citations
A hereditary syndrome with retinopathy and ataxia or deafness in two consanguineous brothers
AbstractOf two brothers born of Sephardic first cousin parents one presented with congenital neural deafness, nyctalopia, visual field loss, flat ERG, unintelligible speech and a shuffling gait, and the other with severe ataxia, severe decreased visual acuity, mild field loss, decreased ERG, dysarthric speech and high grade myopia. The diagnosis of Usher syndrome type 1 or 2 is discussed as well as the possibility that both brothers have different genetic disorders.
[Clinical phenotype and genotype analysis of the family with the Usher syndrome].
AbstractOBJECTIVE: To detect potential variants in a family affected with Usher syndrome type I, and analyze its genotype-phenotype correlation. METHODS: Clinical data of the family was collected. Potential variants in the proband were detected by high-throughput sequencing. Suspected variants were verified by Sanger sequencing. RESULTS: The proband developed night blindness at 10 year old, in addition with bilateral cataract and retinal degeneration. Hearing loss occurred along with increase of age. High-throughput sequencing and Sanger sequencing revealed that she has carried compound heterozygous variants of the MYO7A gene, namely c.2694+2T>G and c.6028G>A. Her sister carried the same variants with similar clinical phenotypes. Her daughter was heterozygous for the c.6028G>A variant but was phenotypically normal. CONCLUSION: The clinical features and genetic variants were delineated in this family with Usher syndrome type I. The results have enriched the phenotype and genotype data of the disease and provided a basis for genetic counseling.
UP Journal of Ophthalmology · 2023 · 0 citations · open access
Usher Syndrome: A Rare Case
AbstractUsher syndrome is a rare heterogenous autosomal recessive genetic disorder with features of visual impairment due to retinitis pigmentosa and hearing loss. Other names for it include Hallgren syndrome, Usher-Hallgren syndrome, retinitis pigmentosa-dysacusis syndrome, and dystrophia retinae dysacusis syndrome.1,2 Usher syndrome represents a genetically diverse condition that involves both early onset sensorineural hearing loss and retinal pathology. While reports of disease prevalence vary, the condition has been estimated to occur in three in 100, 000 individuals.
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.
