DeCure for Autosomal dominant nonsyndromic hearing loss 58
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal dominant nonsyndromic hearing loss 58 — 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 moduleAutosomal dominant nonsyndromic hearing loss 58 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 autosomal dominant nonsyndromic hearing loss 58 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
pleckstrin (PLEK) — PLEK 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 1r,2r,3r,4r,5s,6sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2I5F · 1.35 Å · ligand (1R,2R,3R,4R,5S,6S)-6-HYDROXYCYCLOHEXANE-1,2,3,4,5-PENTAYL PENTAKIS[DIHYDROGEN (PHOSPHATE)] (5IP). Experimental structure, not a prediction.
What the evidence adds up to
Hearing loss affects about 4% of people under 45 years of age. Approximately 30% of genetically determined deafness occurs in syndromic form and 70% in nonsyndromic form. To date, 119 nonsyndromic genes have been associated with hearing loss. Identifying hearing loss genes coupled with clinical characteristics yields a more accurate diagnosis and prognosis.
For autosomal recessive hearing loss DFNB7/11 caused by pathogenic variants in the TMC1 gene, the prevailing auditory phenotype is congenital, profound, bilateral hearing loss. In a retrospective analysis of a single Italian otolaryngology clinic, DFNB7/11 was diagnosed in 3 patients from 2 non-consanguineous families. A novel disease-causing variant in TMC1 was detected: c.962G>A p.(Trp321*). All affected children showed prelingual, severe-to-profound hearing loss.
After cochlear implantation, these 3 patients showed an excellent functional outcome. Speech perception, nonverbal cognition, and speech performance were comparable to those of patients with DFNB1 deafness. The authors state that their results do not support the variable auditory outcome reported in the literature, which may be affected by social, environmental, and genetic background factors.
No drug treatment is described in any of these abstracts. What is still missing for autosomal dominant nonsyndromic hearing loss 58 specifically is any clinical trial of a pharmacological intervention, any molecular characterisation of the DFNA58 locus in a format that could guide drug repurposing, and any patient stratification beyond the audiologic phenotype.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Neurology · 1999 · 11 citations
Vestibular and hearing loss in genetic and metabolic disorders
AbstractHearing loss affects about 4% of people under 45 years of age and comprises a broad spectrum of clinical presentations (congenital or late-onset, conductive or sensorineural, and syndromic or nonsyndromic). Approximately 30% of genetically determined deafness is reported to occur in syndromic form and 70% in nonsyndromic form. This review highlights recent advances in the molecular and genetic basis of hearing loss, which will help in understanding the biology of normal and abnormal hearing.
Genetics of pediatric hearing loss: A functional perspective
AbstractOBJECTIVES: This article reviews the current role of genetics in pediatric hearing loss (HL). METHODS: A review of the current literature regarding the genetic basis of HL in children was performed. RESULTS: To date, 119 nonsyndromic genes have been associated with HL. There are also hundreds of syndromic causes that have HL as part of the clinical phenotype. CONCLUSIONS: Identifying HL genes coupled with clinical characteristics ("genotype-phenotype") yields a more accurate diagnosis and prognosis. Although the complexity of the auditory apparatus presents challenges, gene therapy is emerging and may be a viable management option in the future.
Supplementary Material for: Auditory Outcome after Cochlear Implantation in Children with DFNB7/11 Caused by Pathogenic Variants in <b><i>TMC1</i></b> Gene
Abstract<b><i>Introduction:</i></b> Non-syndromic hereditary hearing loss is characterized by extreme genetic heterogeneity. So far, more than 100 pathogenic or likely pathogenic variants in <i>TMC1</i> gene have been reported in patients with autosomal recessive hearing loss (HL) DFNB7/11. The prevailing auditory phenotype of individuals with DFNB7/11 is congenital, profound, bilateral HL, but the functional outcome after cochlear implantation (CI) described in the literature is variable. The objective of this work is to evaluate the auditory outcome after CI in pediatric patients with DFNB7/11, born to non-consanguineous parents. <b><i>Methods:</i></b> A retrospective analysis of genetic and audiological data of DFNB7/11 patients followed up in a single Italian otolaryngology clinic was performed. Cases with biallelic pathogenic variants in <i>TMC1</i> were selected from the cohort of children with non-syndromic hearing loss who had undergone CI and had been molecularly characterized by multigene panel testing. All patients underwent extensive audiological assessment, and the auditory outcome after CI was evaluated. <b><i>Results:</i></b> DFNB7/11 was diagnosed in a total of 3 patients from 2 non-consanguineous families; a novel disease-causing variant in <i>TMC1</i> was detected [c.962G>A p.(Trp321*)]. All the affected children showed the typical DFNB7/11 phenotype characterized by prelingual, severe-to-profound HL. The patients showed an excellent functional outcome after CI; speech perception, nonverbal cognition, and speech performance were comparable to those of patients with DFNB1 deafness. <b><i>Discussion/Conclusion:</i></b> Our results do not support the variable auditory outcome reported in the literature, which may be affected by several social and environmental factors and by the genetic background.
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.
