DeCure for Autosomal recessive nonsyndromic hearing loss 30
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal recessive nonsyndromic hearing loss 30 — 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 moduleAutosomal recessive nonsyndromic hearing loss 30 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 autosomal recessive nonsyndromic hearing loss 30 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
myosin IIIA (MYO3A) — MYO3A 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 6JLE · 1.55 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Non-syndromic hereditary hearing loss is genetically highly heterogeneous. By 2003, 80 genetic loci and 30 genes had been mapped for the non-syndromic form; by 2020, 119 non-syndromic genes had been associated with hearing loss in children, alongside hundreds of syndromic causes. The identified genes span diverse protein classes including myosins, cytoskeletal proteins, channel and gap junction components, transcription factors, and extracellular matrix proteins. For autosomal recessive non-syndromic hearing loss specifically, six genes had been isolated by 2000, with an estimated 50 to 80 hearing loss genes still undiscovered at that time.
One specific form, DFNB7/11, is caused by biallelic pathogenic variants in the TMC1 gene. A 2020 study of three children from two non-consanguineous Italian families with DFNB7/11 found a novel disease-causing variant, c.962G>A p.(Trp321*). All three children had the typical phenotype of prelingual, severe-to-profound bilateral hearing loss. After cochlear implantation, their speech perception, non-verbal cognition, and speech performance were comparable to those of children with DFNB1 deafness. The authors state that their results do not support the variable auditory outcome reported elsewhere in the literature, which they suggest may be influenced by social, environmental, and genetic background factors.
Gene therapy is emerging as a potential future management option, with the OTOF gene cited as an exemplar for delivering a correct gene copy to a specific target cell in the inner ear to restore cochlear function. However, no gene therapy has been approved or tested in humans for autosomal recessive non-syndromic hearing loss 30 or any other form of this condition. The complexity of the auditory apparatus remains a major challenge.
What is still missing are large, well-controlled clinical trials of gene therapy or other molecular treatments for this specific genetic subtype. Patient stratification by exact mutation and residual function is not yet standardised. Funding for such trials, particularly for rare recessive forms like DFNB7/11, remains limited.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Ear and Hearing · 2003 · 66 citations
Nonsyndromic Hearing Loss
AbstractIn Brief The past decade has seen extremely rapid progress in the field of hereditary hearing loss. To date, 80 loci for nonsyndromic hearing loss have been mapped to the human genome. Furthermore, 30 genes have been identified. These genes belong to a wide variety of protein classes: from myosins and other cytoskeletal proteins, over channel and gap junction components, to transcription factors, extracellular matrix proteins and genes with an unknown function. The identification of these genes has enabled geneticists to offer DNA diagnostic tests for some types of nonsyndromic hearing loss. Moreover, it holds the promise to significantly improve the molecular knowledge on the auditory and vestibular organs and on the pathological mechanisms leading to hearing loss. This opens perspectives for future therapeutic and/or preventive measures for hearing loss. This review attempts to give an overview of the current knowledge of the genes responsible for nonsyndromic hearing loss, their expression and functions in the cochlea. A broad review of genes responsible for nonsyndromic hearing loss, their expression and function in the cochlea. Also discusses the genetic tests currently offered for different types of nonsyndromic hearing loss.
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.
Journal of the American Academy of Audiology · 2021 · 4 citations
Genetic Medicine for Hearing Loss: <i>OTOF</i> as Exemplar
AbstractAbstract Millions of people worldwide have disabling hearing loss because one of their genes generates an incorrect version of some specific protein the ear requires for hearing. In many of these cases, delivering the correct version of the gene to a specific target cell within the inner ear has the potential to restore cochlear function to enable high-acuity physiologic hearing. Purpose: In this review, we outline our strategy for the development of genetic medicines with the potential to treat hearing loss. We will use the example of otoferlin gene ( OTOF )-mediated hearing loss, a sensorineural hearing loss due to autosomal recessive mutations of the OTOF gene.
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.
Zurich Open Repository and Archive (University of Zurich) · 2000 · 0 citations · open access
Erbliche Schwerhörigkeit: neue Möglichkeiten der Diagnostik
AbstractMutations in many different genes can result in hearing loss. Using different molecular genetic methods, the disease-causing gene mutations can often be identified or at least localised to defined regions of the genome. These new diagnostic possibilities result from the localisation and identification of a number of hearing-loss genes in the last five years. Diagnostic investigations should always be accompanied by a genetic counselling of the family. In addition, the isolation thus far of 11 genes mutated in autosomal dominant inherited hearing loss, as well as of 6 genes mutated in autosomal recessive inherited hearing loss, has contributed to a better understanding of the molecular pathology of hearing loss in general. However, we are only beginning to see the whole picture, as an estimated 50 to 80 hearing loss genes remain to be discovered.
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.
