DeCure for Autosomal dominant nonsyndromic hearing loss 13
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal dominant nonsyndromic hearing loss 13 — 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 13 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 13 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
A 1996 study of a single large North American family with autosomal dominant progressive sensorineural hearing loss found that the condition began around age 20 and became profound by about age 45. The family was large enough and two temporal bones from affected members were available, allowing a detailed description of the mutation’s effects. No drug or intervention was tested.
A 2014 study of two Korean families with autosomal dominant nonsyndromic hearing loss identified two novel mutations in the TECTA gene, which accounts for about 4% of autosomal dominant cases in some populations. One mutation (c.3995G>T, p.C1332F) was associated with stable high-frequency hearing loss; the other (c.5618C>T, p.T1873I) with stable mid-frequency hearing loss. The cysteine-to-phenylalanine change in the first family was not linked to progression of hearing loss, contradicting an earlier hypothesis. The authors suggested that patients with the vWFD3-D4 interdomain mutation might be good candidates for middle ear implantation, but no such implantation was performed in the study.
A 2004 study of 144 patients with nonsyndromic hearing loss described sex distribution, type, degree, symmetry, laterality, progression, aetiology, and inheritance patterns, but did not test any drug or treatment. A 2000 German review noted that by that time 11 genes for autosomal dominant and 6 for autosomal recessive nonsyndromic hearing loss had been isolated, but estimated that 50 to 80 hearing loss genes remained undiscovered. A 1999 review of autosomal dominant hearing impairment genotypes emphasised the need for detailed phenotyping to support genetic counselling and gene discovery.
No drug has been studied for autosomal dominant nonsyndromic hearing loss 13 in any of these abstracts. What is missing is any clinical trial of a pharmacological intervention, any attempt at gene therapy or molecular correction, and any systematic patient stratification beyond broad audiometric categories. Funding for preclinical work and for trials that could test hearing preservation or restoration in defined TECTA mutation carriers is absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Otology & Neurotology · 2004 · 32 citations
Early Onset and Rapid Progression of Dominant Nonsyndromic DFNA36 Hearing Loss
AbstractOBJECTIVE: To characterize the auditory and vestibular phenotype of autosomal dominant nonsyndromic DFNA36 hearing loss. STUDY DESIGN: Clinical evaluation of individuals with DFNA36 hearing loss linked to the D572N mutation of transmembrane channel-like gene 1 (TMC1). Medical history interviews, physical examinations, and pure-tone air conduction audiometry were performed in the field. Audiology and radiology reports were available and retrospectively reviewed for a subset of subjects. SETTING: Primary, secondary, and tertiary referral centers (retrospectively reviewed studies); subjects' homes (prospective clinical evaluations). PATIENTS: Thirteen affected members of a North American Caucasian family segregating DFNA36 hearing loss. MAIN OUTCOME MEASURES: Pure-tone audiometric thresholds and their rates of progression. RESULTS: Subjects had bilateral, symmetric, sensorineural hearing loss with a postlingual onset in the first decade of life. High frequencies were initially affected, followed by rapid progression (5.9 dB/yr for the 0.5/1/2/4-kHz pure-tone average) to profound deafness across all frequencies by the second decade of life. Two individuals had excellent auditory-verbal communication after rehabilitation with cochlear implants placed over two decades after total deafening. CONCLUSIONS: DFNA36 has one of the earliest onsets and most rapid rates of progression among the autosomal dominant non-syndromic hearing loss phenotypes. These distinctive features should facilitate its clinical detection and the development of clinical-molecular genetic diagnostic algorithms for dominant nonsyndromic hearing loss.
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.
British Journal of Audiology · 1999 · 23 citations
Non-Syndromal Autosomal Dominant Hearing Impairment: Ongoing Phenotypical Characterization of Genotypes
AbstractThis review is concerned with the present state of phenotypical characterization of known genotypes of non-syndromal autosomal dominant hearing impairment. A brief outline of history and context of phenotyping and genotyping of hearing impairment is given with particular reference to the most recent developments in this field, followed by descriptions of DFNA1, DFNA2, DFNA5, DFNA6/14, DFNA8/12, DFNA9, DFNA 13, DFNA17 and DFNA21. Phenotyping those known genotypes may support the ongoing search for mutations in the corresponding gene and enhance genetic counselling. It is recommended that sufficient attention is given to a detailed description of the phenotype in each (newly) described hereditary hearing impairment disorder.
Novel <b><i>TECTA </i></b>Mutations Identified in Stable Sensorineural Hearing Loss and Their Clinical Implications
AbstractTECTA is a causative gene of autosomal dominant (DFNA8/A12) and autosomal recessive (DFNB 21) nonsyndromic sensorineural hearing loss (NSHL). Mutations in TECTA account for 4% of all autosomal dominant NSHL cases in some populations and are thus thought to be one of the major causes of autosomal dominant NSHL. A genotype-phenotype correlation for autosomal dominant mutations in the TECTA gene has been proposed. Two families (SB146 and SB149), which segregated moderate NSHL in an autosomal dominant fashion, were included in this study. We performed targeted resequencing of 134 known deafness genes (TRS-134) and bioinformatics analyses to find causative mutations for NSHL in these 2 families. Through TRS-134, we detected 2 novel mutations, i.e. c.3995G>T (p.C1332F) and c.5618C>T (p.T1873I), in the TECTA gene. These mutations cosegregated with NSHL in the studied families and were not detected in normal controls. The mutations c.3995G>T and c.5618C>T reside in the von Willebrand factor type D3-D4 (vWFD3-D4) interdomain of the zonadhesin (ZA) domain and the zona pellucida (ZP) domain, respectively. p.C1332F is the first mutation detected in the vWFD3-D4 interdomain of the ZA domain. The mutations p.C1332F and p.T1873I were associated with stable high-frequency and mid-frequency hearing loss, respectively. Notably, the cysteine residue mutated to phenylalanine in SB146 was not related to progression of sensorineural hearing loss, which argues against the previous hypothesis. Here we confirm a known genotype-phenotype correlation for the ZP domain and propose a hypothetical genotype-phenotype correlation which relates mutations in vWFD3-D4 to stable high-frequency NSHL in Koreans. This clinical feature makes subjects with the missense mutation in the vWFD3-D4 interdomain of TECTA potentially good candidates for middle ear implantation.
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.
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.
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.
