DeCure for Autosomal dominant nonsyndromic hearing loss
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal dominant nonsyndromic hearing loss — screening already-approved drugs against its 34-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 maps to a 34-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 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
tenascin C (TNC) — TNC 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 3-methyl-1,2,4-thiadiazol-5-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5R61 · 1.38 Å · ligand 1-(3-methyl-1,2,4-thiadiazol-5-yl)-1,4-diazepane (K1P). Experimental structure, not a prediction.
What the evidence adds up to
Hearing loss affects about 4% of people under 45 and is genetically highly heterogeneous. Approximately 70% of genetically determined deafness is nonsyndromic. By 2000, 11 genes for autosomal dominant and 6 for autosomal recessive nonsyndromic hearing loss had been isolated, with an estimated 50 to 80 hearing-loss genes still undiscovered. By 2014, more than 100 genetic loci were associated with nonsyndromic hearing loss, and by 2020, 119 nonsyndromic genes had been identified. The disorder can be inherited in autosomal dominant, autosomal recessive, X-linked recessive, and mitochondrial patterns.
For the specific autosomal recessive form DFNB7/11, caused by pathogenic variants in the TMC1 gene, a 2020 study of 3 patients from 2 non-consanguineous families in a single Italian clinic found that all children had the typical phenotype of prelingual, severe-to-profound hearing loss. After cochlear implantation, these patients showed an excellent functional outcome, with speech perception, nonverbal cognition, and speech performance comparable to patients with DFNB1 deafness. The authors note that their results do not support the variable auditory outcome reported elsewhere in the literature, which they suggest may be affected by social, environmental, and genetic background factors.
No drug treatment for autosomal dominant nonsyndromic hearing loss is described in any of these abstracts. The 2020 review mentions that gene therapy is emerging and may be a viable management option in the future, but this is not a present intervention. The 2014 review states that identifying genes is essential for diagnosis and rehabilitation and opens new perspectives in treatment, but no specific therapy is reported.
What is still missing is any drug therapy that has been tested in patients with this condition. The abstracts describe only cochlear implantation as a current management option for severe cases. No clinical trial of a pharmacological agent for autosomal dominant nonsyndromic hearing loss is reported. The genetic complexity — with over 100 loci and many undiscovered genes — means that patient stratification for any future therapy would be difficult. Funding for drug development in this rare, genetically diverse disorder remains absent from these records.
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.
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.
Medicinos teorija ir praktika · 2014 · 0 citations
Hereditary hearing loss. Genetic factors in ethiopathogenesis of deafness
AbstractCongenital hearing loss is one of the most common defects diagnosed 1 in 1000 newborns. Prelingual hearing loss disturbs development of the child and it is one of disabling conditions in present day environment. It is a highly heterogeneous disorder, with the majority of cases having genetic etiology. Ear is a very complex organ, proper development of the tissues in macroscopic, microscopic and molecular levels and function are essencial for the perception of sound. These processes are influenced mostly by genetic factors. Recent advances in the gene identification techniques have revolutionized the clinical approach to congenital hearing loss. More than 400 and 100 genetic loci are associated with syndromic and nonsyndromic hearing loss respectively. High heterogeneity of hearing loss is important in genetic counselling – the disorder may be inherited in autosomal dominant, autosomal recessive, X recessive and mitochondrial manner. In this review we discuss the structure and the function of auditory organ, the pathogenic mechanisms of hearing loss and provide the clinical approach. The identification of genes implicated in pathogenesis of hearing loss is essential in establishing of genetic diagnosis and rehabilitation, opens new perspectives in treatment, and allows predicting the severity of the disorder, progression and effectiveness of rehabilitating measures.
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.
