DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Usher syndrome type 1F — 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 moduleUsher syndrome type 1F 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 usher syndrome type 1f 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.
What the evidence adds up to
Usher syndrome type 1F is one of several genetically distinct Usher syndromes, which share the core features of hearing loss and rod-cone dystrophy (retinitis pigmentosa), with vestibular dysfunction present in many patients. A 1994 paper describes clinical criteria adopted by the Usher Syndrome Consortium for diagnosing type I and type II, but does not provide any treatment or outcome data. A 2017 study of 138 patients clinically diagnosed with Usher syndrome achieved a molecular diagnosis in 97% of both USH1 and USH2 patients, with biallelic mutations found in 97% of USH1 and 90% of USH2 cases. That study also demonstrated that the drug PTC124 (ataluren) can induce read-through of the common USH2A p.Trp3955* nonsense mutation (found in 13% of detected USH2A alleles) in a laboratory setting, but no clinical outcomes in patients are reported. No abstract in this set specifically addresses type 1F.
A 2013 study of 18 subjects from nine families with Usher syndrome type IIA found that hearing loss severity varied from mild to profound even among siblings with identical USH2A mutations, and no significant differences in hearing thresholds were found between groups with different mutations. The authors concluded that other variables — modifying genes, epigenetics, or environmental factors — likely modulate the phenotype. A 2020 review notes that "atypical" Usher syndrome presentations have been reported with wide phenotypic deviations from classical descriptions, and calls for clearer nomenclature. A 2020 case report of one family with MYO7A mutations (Usher type I) describes a proband with night blindness at age 10, bilateral cataract, retinal degeneration, and progressive hearing loss, but provides no treatment or survival data.
What is still missing: no clinical trial has tested any drug in Usher syndrome type 1F patients; no abstract reports a therapy that slows or reverses vision or hearing loss in any Usher subtype; the genetic and phenotypic heterogeneity means that any future trial will need careful patient stratification by genotype and baseline function; funding for such trials remains scarce.
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.
Molecular Genetics & Genomic Medicine · 2017 · 66 citations · open access
Next-generation sequencing reveals the mutational landscape of clinically diagnosed Usher syndrome: copy number variations, phenocopies, a predominant target for translational read-through, and<i>PEX26</i>mutated in Heimler syndrome
AbstractBackground Combined retinal degeneration and sensorineural hearing impairment is mostly due to autosomal recessive Usher syndrome (USH1: congenital deafness, early retinitis pigmentosa (RP); USH2: progressive hearing impairment, RP). Methods Sanger sequencing and NGS of 112 genes (Usher syndrome, nonsyndromic deafness, overlapping conditions), MLPA, and array-CGH were conducted in 138 patients clinically diagnosed with Usher syndrome. Results A molecular diagnosis was achieved in 97% of both USH1 and USH2 patients, with biallelic mutations in 97% (USH1) and 90% (USH2), respectively. Quantitative readout reliably detected CNVs (confirmed by MLPA or array-CGH), qualifying targeted NGS as one tool for detecting point mutations and CNVs. CNVs accounted for 10% of identified USH2A alleles, often in trans to seemingly monoallelic point mutations. We demonstrate PTC124-induced read-through of the common p.Trp3955* nonsense mutation (13% of detected USH2A alleles), a potential therapy target. Usher gene mutations were found in most patients with atypical Usher syndrome, but the diagnosis was adjusted in case of double homozygosity for mutations in OTOA and NR2E3, genes implicated in isolated deafness and RP. Two patients with additional enamel dysplasia had biallelic PEX26 mutations, for the first time linking this gene to Heimler syndrome. Conclusion Targeted NGS not restricted to Usher genes proved beneficial in uncovering conditions mimicking Usher syndrome.
Structures of Usher Syndrome 1 Proteins and Their Complexes
AbstractUsher syndrome 1 (USH1) is the most common and severe form of hereditary loss of hearing and vision. Genetic, physiological, and cell biological studies, together with recent structural investigations, have not only uncovered the physiological functions of the five USH1 proteins but also provided mechanistic explanations for the hearing and visual deficiencies in humans caused by USH1 mutations. This review focuses on the structural basis of the USH1 protein complex organization.
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.
[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.
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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