DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hearing loss, autosomal dominant 74 — 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 moduleHearing loss, autosomal dominant 74 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 hearing loss, autosomal dominant 74 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 genome search in an extended Dutch family with autosomal dominant progressive high-frequency hearing loss localised the causative gene to chromosome 7p15, in a 15 cM interval between markers D7S493 and D7S632. A separate study reported a novel heterozygous 605G→T mutation in the GJB2 gene, causing a C202F substitution in the fourth transmembrane domain of connexin26, in all affected members of a large family with late childhood onset of autosomal dominant isolated hearing loss. That study noted that GJB2 mutations account for up to 50% of autosomal recessive hearing loss but only one dominant GJB2 mutation had been reported before.
In Fabry disease, data from the Fabry Outcome Survey covering 566 patients found that 316 reported ear-related symptoms. Pure-tone audiograms from 86 patients before enzyme replacement therapy showed that 74% had a threshold elevated above the 95th centile in at least one frequency compared to age-matched norms. However, only 16% (14 patients) met the age-independent WHO definition of clinically relevant hearing impairment (mean threshold at 0.5, 1, and 2 kHz worse than 25 dB). Hearing loss was sensorineural in 73% of patients, and men were affected earlier and more severely than women. The pattern resembled accelerated presbycusis with an additional strial-type component.
A review of aminoglycoside- and cisplatin-induced ototoxicity stated that as many as 1 million people per year in Western Europe and North America acquire hearing loss from these hospital-prescribed medications. The review noted that no federally approved drugs exist to prevent or treat this permanent hearing loss. In a separate retrospective study of cochlear implantation in 14 patients deafened by ototoxic drugs, post-operative Bamford-Kowal-Bench scores ranged from 33 to 100% (median 91%). These outcomes were not statistically different from those in 13 patients with sudden sensorineural hearing loss (median 88%, P=0.983). One patient in the ototoxic group required explantation following infection.
A UK National Health Service clinic study estimated that 6.7% of the local clinical population and 0.7% of the general population have hearing loss greater than 70 dB averaged over 0.5, 1, and 2 kHz. The authors noted this probably underestimates true prevalence. What remains missing for autosomal dominant hearing loss DFNA5 specifically is any clinical trial of a drug therapy, any identified molecular target for intervention, and any patient stratification beyond the original linkage to chromosome 7p15. Funding for basic research into the DFNA5 gene product and its mechanism, as well as for designing and recruiting to a trial, 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.
Human Molecular Genetics · 1995 · 103 citations
Localization of a gene for non-syndromic hearing loss (DFNA5) to chromosome 7p15
AbstractProgressive hearing loss affects approximately 50% of the elderly by the age of 80, and is most likely caused by an interaction of genetic and environmental factors. Identification of the genes responsible for hereditary hearing loss is therefore important. Families with pure genetic degenerative hearing disorders may be helpful as the same genes may be also involved in age-related hearing loss in general. In this study we have performed a genome search in an extended Dutch family with autosomal dominant progressive hearing loss starting in the high frequencies. The gene causing hearing loss in this family was localized to the short arm of chromosome 7, in a 15 cM interval between markers D7S493 and D7S632.
American Journal of Audiology · 2021 · 74 citations · open access
Mechanisms of Aminoglycoside- and Cisplatin-Induced Ototoxicity
AbstractPurpose This review article summarizes our current understanding of the mechanisms underlying acquired hearing loss from hospital-prescribed medications that affects as many as 1 million people each year in Western Europe and North America. Yet, there are currently no federally approved drugs to prevent or treat the debilitating and permanent hearing loss caused by the life-saving platinum-based anticancer drugs or the bactericidal aminoglycoside antibiotics. Hearing loss has long-term impacts on quality-of-life measures, especially in young children and older adults. This review article also highlights some of the current knowledge gaps regarding iatrogenic causes of hearing loss. Conclusion Further research is urgently needed to further refine clinical practice and better ameliorate iatrogenic drug-induced hearing loss.
European Journal of Clinical Investigation · 2006 · 68 citations · open access
Hearing loss in Fabry disease: data from the Fabry Outcome Survey
AbstractHearing loss is a common symptom in Fabry disease, but neither its natural course nor its aetiology has been defined precisely. The aim of this study was to provide a detailed epidemiological description of hearing impairment in patients in the Fabry Outcome Survey (FOS), which is the largest available database of Fabry patients. Questionnaires were completed by 566 Fabry patients, of whom 316 reported ear-related symptoms. Pure-tone audiograms from 86 patients, performed before starting enzyme replacement therapy, were analysed and compared with age- and sex-specific normal values (International Organization for Standardization, ISO 7029). When compared to an age-matched population (ISO 7029), 74% of patients had a threshold elevated above the 95th centile in at least one tested frequency. All frequencies were affected to a similar degree. However, only 14 patients (16%) were clinically affected by hearing impairment according to the age-independent World Health Organization (WHO) classification (mean threshold at 0.5, 1 and 2 kHz worse than 25 dB). Hearing loss was sensorineural in 63 patients (73%) of whom 7 patients (8%) had also a conductive component. One patient had a purely conductive hearing loss. Episodes of sudden hearing loss seemed to occur more frequently than in the general population. Men were affected earlier and more severely than women. Hearing in Fabry disease is significantly worse than in an age-matched general population but leads to clinically relevant hearing impairment in only 16% of cases. It resembles accelerated presbycusis with an additional Fabry-specific strial-type hearing loss.
Journal of Medical Genetics · 2000 · 67 citations · open access
A novel C202F mutation in the connexin26 gene (<i>GJB2</i>) associated with autosomal dominant isolated hearing loss
AbstractMutations in the GJB2 gene encoding connexin26 (CX26) account for up to 50% of cases of autosomal recessive hearing loss. In contrast, only one GJB2 mutation has been reported to date in an autosomal dominant form of isolated prelingual hearing loss. We report here a novel heterozygous 605G-->T mutation in GJB2 in all affected members of a large family with late childhood onset of autosomal dominant isolated hearing loss. The resulting C202F substitution, which lies in the fourth (M4) transmembrane domain of CX26, may impair connexin oligomerisation. Finally, our study suggests that GJB2 should be screened for heterozygous mutations in patients with autosomal dominant isolated hearing impairment, whatever the severity of the disease.
International Journal of Audiology · 2012 · 32 citations
Prevalence & characteristics of severe and profound hearing loss in adults in a UK National Health Service clinic
AbstractLaura Turton*ab & Pauline Smithcda Hearing Link, Eastbourne, UKb The Centre for Hearing & Balance Disorders, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UKc Hearing Services Department, University Hospitals of Leicester NHS Trust, Leicester, UKd Medical Research Council Hearing and Communication Group, Royal Free London NHS Foundation Trust, London, UKCorrespondence: Laura Turton, Hearing Link, 27–28, The Waterfront, Eastbourne, East Sussex, BN23 5UZ, UK. E-mail:[email protected]: To estimate the prevalence of severe and profound hearing loss in a clinical population and to report the audiological and hearing-aid characteristics for this group, as well as outcome measures from use of hearing aids. Design: A retrospective observational study initially, followed by a postal Glasgow health status inventory (GHSI) to establish the patients functional outcomes. Study sample: A clinical database of 32 781 cases was interrogated from which 2199 cases of severe /profound hearing loss were identified. From these, an adult sample stratified in terms of age and gender of n = 302 was contacted. Results: An estimated 6.7% of the local clinical population and 0.7% of the general population were found to have hearing > 70 dB averaged over 0.5, 1, and 2 kHz. Most patients were fitted with bilateral hearing aids, using a non-linear prescription, and as a group they reported a high level of social support. Conclusions: This study has estimated the prevalence of severe and profound hearing loss as 6.7% of the clinical population, and 0.7% of the general population. This is consistent with previous work, although it probably underestimates the prevalence. Further work is indicated to strengthen the estimate.
Cochlear Implants International · 2013 · 14 citations
Cochlear implantation in patients deafened by ototoxic drugs
AbstractOBJECTIVE: To investigate the outcome of cochlear implantation (CI) in patients deafened by ototoxic drugs and to compare this, with the outcome of CI in sudden sensorineural hearing loss (SSNHL) with a similar duration of deafness. METHODS: The Manchester Auditory Implant Centre database was reviewed to identify patients who were implanted to rehabilitate profound sensorineural hearing loss resulting from treatment with ototoxic agents and patients with SSNHL group. A retrospective case note review of selected patients was carried out. Primary outcome measure was post-implantation Bamford-Kowal-Bench (BKB) score in quiet in both the groups. Secondary outcome measure was any significant complications following implantation. RESULTS: We identified 14 patients in the ototoxic group, which were matched with 13 patients in the SSNHL group. The post-operative BKB score in the ototoxic group ranged from 33 to 100% (median score 91%). One patient had bilateral CI. One patient required explantation following an infection. The post-operative BKB score in the SSNHL group ranged from 16 to 100% (median score 88%). One patient in this group could not be tested using this method as they did not have open set speech discrimination. Two patients in this group had bilateral CI. The data were analysed using Mann-Whitney U test. There was no statistically significant difference in the BKB scores in the two groups of patients (P value -0.983). CONCLUSION: Patients with profound hearing loss secondary to ototoxic agents can be rehabilitated successfully with CI. The outcomes may be variable and may be dependent on the underlying pathology for which the ototoxic agents were prescribed.
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.
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