DeCure for Autosomal dominant nonsyndromic hearing loss 3A
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal dominant nonsyndromic hearing loss 3A — 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 dominant nonsyndromic hearing loss 3A 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 dominant nonsyndromic hearing loss 3a 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
Forty-nine members of a single North American family with autosomal-dominant progressive sensorineural hearing loss were evaluated in 1996. The hearing loss began at about age 20 and became profound by approximately age 45. A 2004 study examined 144 patients with nonsyndromic hearing loss, describing sex distribution, type, degree, symmetry, laterality, progression, and inheritance pattern, but did not report any drug intervention or treatment outcome.
A 2020 study of cochlear implantation in children with DFNB7/11, caused by pathogenic variants in the TMC1 gene, included only 3 patients from 2 non-consanguineous families. All had prelingual, severe-to-profound hearing loss. After cochlear implantation, speech perception, nonverbal cognition, and speech performance were comparable to those of patients with DFNB1 deafness. The authors state that this result does not support the variable auditory outcome reported elsewhere in the literature. No drug was tested or mentioned in any of these abstracts.
A 2000 review noted that by that year, 11 genes for autosomal dominant hearing loss and 6 for autosomal recessive hearing loss had been isolated, but estimated that 50 to 80 hearing-loss genes remained undiscovered. No drug, no trial, and no treatment for autosomal dominant nonsyndromic hearing loss 3A is described in any of these papers. What is missing is any clinical trial of a pharmacological agent for this specific condition, any funded drug-repurposing study, and any patient stratification beyond the broad categories of age at onset and severity.
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 Audiology · 1996 · 24 citations
Autosomal-Dominant Progressive Sensorineural Hearing Loss in a Large North American Family
AbstractForty-nine members of a family with autosomal-dominant progressive sensorineural hearing loss were evaluated by audiologists, otologists, and geneticists. The results presented here show a nonsyndromic, autosomal-dominant mutation causing progressive sensorineural hearing loss beginning at about age 20 and becoming profound by approximately age 45. Because of the unambiguous nature of the hearing loss, the size of the family, and the availability of two previously described temporal bones from family members, a fairly complete description of the nature and impact of this mutation will be presented.
American Journal of Audiology · 2004 · 1 citations
Clinical Genetic Study of 144 Patients With Nonsyndromic Hearing Loss
AbstractHearing loss constitutes an important category of congenital defects that can be isolated or part of the phenotypic spectrum of several syndromes. A clinical genetic study was performed on a sample of 144 patients with nonsyndromic hearing loss, establishing the sex distribution, type, degree, symmetry, laterality, progression, etiology, and, when possible, inheritance pattern.
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.
