DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hearing loss, autosomal dominant 77 — 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 77 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
approvedZoledronateApproved drug
Structures already discussed alongside hearing loss, autosomal dominant 77 in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of human FPPS — Zoledronate has a real, experimentally solved structure in complex with this target (PDB 2F9K, 2.06 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet zoldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2F9K · 2.06 Å · ligand Zoledronate (ZOL). Experimental structure, not a prediction.
What the evidence adds up to
A novel C202F mutation in the connexin26 gene (GJB2) was found in all affected members of a large family with late childhood onset of autosomal dominant isolated hearing loss. The mutation is a heterozygous 605G→T change resulting in a C202F substitution in the fourth transmembrane domain of CX26, which may impair connexin oligomerisation. Only one other GJB2 mutation had been reported in autosomal dominant isolated prelingual hearing loss before this 2000 study. The authors suggest screening GJB2 for heterozygous mutations in patients with autosomal dominant isolated hearing impairment regardless of severity.
In a 2012 UK NHS clinic study of 32,781 cases, 2,199 cases of severe or profound hearing loss were identified. An estimated 6.7% of the local clinical population and 0.7% of the general population had hearing greater than 70 dB averaged over 0.5, 1, and 2 kHz. Most patients were fitted with bilateral hearing aids using a non-linear prescription and reported a high level of social support. The authors note this probably underestimates prevalence and that further work is needed.
A 2025 review on gene therapy for hereditary hearing loss states that gene therapy involves genetic modification to repair or reconstruct faulty genetic material. It describes three major strategies: gene replacement, gene suppression, and gene editing. The review notes recent approval of clinical trial results using gene therapy for hereditary hearing loss and summarises successful preclinical trials. Another 2025 expert consensus on surgical treatment for hereditary hearing loss, based on molecular epidemiological survey data and postoperative follow-up, provides guidance for surgical methods, efficacy evaluation, and postoperative rehabilitation.
What is still missing is a specific gene therapy or drug tested for the C202F GJB2 mutation or for autosomal dominant hearing loss in general. No clinical trial results for any drug in this specific genetic form of hearing loss are reported in these abstracts. The prevalence data come from a single UK clinic and may underestimate the true population burden. No patient stratification by genotype is applied in the surgical consensus or the prevalence study.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
Third‐generation bisphosphonates for cochlear otosclerosis stabilizes sensorineural hearing loss in long‐term follow‐up
AbstractObjective: To assess long-term hearing outcomes in patients treated with third-generation bisphosphonates for otosclerosis-related progressive sensorineural hearing loss (SNHL). Study Design: Retrospective case series review. Methods: We performed a retrospective case series review of patients with otosclerosis and progressive SNHL. Patients were treated with either risedronate or zoledronate after a diagnosis of otosclerosis with a significant SNHL component. Bone conduction pure tone threshold averages (BC-PTAs) and word recognition scores (WRS) before and after bisphosphonate administration in long-term follow-up was analyzed. Significant change in BC-PTA was defined as greater than 10dB or between 4% and 18% in WRS based on binomial variance. Results: Seven patients were identified and 14 ears met inclusion criteria. Three patients were female and the mean age was 48.3 ± 10.3 years. The mean duration between treatment with bisphosphonate administration and long-term post-treatment follow-up audiometry was 87.6 ± 18.3 months, with a range of 61.6 to 109.1 months and median of 89.2 months. Analysis using BC-PTA and WRS demonstrated that 11 ears remained stable while 2 improved and 1 worsened. No patient experienced any major complication as the result of bisphosphonate therapy. Conclusion: Treatment with third-generation bisphosphonates is associated with stability in otosclerosis-related sensorineural hearing over 5- to 9-year period. These results suggest that such medications may prevent the progression of SNHL in patients with otosclerosis. Level of Evidence: 4 (Case series).
Sensory Neuroscience · 2025 · 7 citations · open access
Update on Gene Therapy in the Treatment of Hereditary Hearing Loss
AbstractABSTRACT Gene therapy is a promising therapeutic approach for genetic disorders, involving genetic modification to repair or reconstruct faulty genetic material. It is particularly relevant to hereditary hearing loss (HHL), a common monogenic condition that can lead to congenital deafness. The recent approval of clinical trial results using gene therapy for HHL underscores the growing interest in this field. To further advance inner ear gene therapy and its application in genetic diseases, it is crucial to review the progress of gene therapy for HHL. This review focuses on the three major gene therapy strategies—gene replacement, gene suppression, and gene editing—highlighting their application across different monogenic disorders and successful preclinical trials in HHL. We summarize the primary gene therapy strategies used in recent years, discuss recent achievements in preclinical studies, and explore potential advancements in this field.
British Journal of Hospital Medicine · 2005 · 4 citations
The genetics of hearing loss
AbstractHearing impairment is the most common sensory deficit with half of the causes of hearing loss having a genetic basis. There is a range of treatment devices but these do not correct the underlying pathology. Advances in molecular biology have greatly enhanced our understanding of the pathophysiology of genetic hearing loss, including potential treatments.
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.
Practica Oto-Rhino-Laryngologica · 1994 · 1 citations · open access
Alpha-Interferon for Severe Idiopathic Sudden Sensorineural Hearing Loss; A New Treatment.
AbstractThe severe type of idiopathic sudden sensorineural hearing loss (ISSHL) was treated with genetic recombination interferon alpha-2a (alpha-IFN) (3 million IU/day for 10 days) plus cortico-steroid, and the results were significantly better than those obtained by conventional treatment with cortico-steroid, vitamins, and vasodilators. Assays for 2'-5' oligoadenylate synthetase (2-5 AS), one of the indices of circulating anti-viral activity were performed patients before and on the third day of IFN therapy, and the levels were found to correlate well with the degree of their hearing improvement. These results suggest that viral infections may be related to the etiology of the severe type of ISSHL and that alpha-Interferon is useful in its treatment.
[Expert consensus on surgical treatment for hereditary hearing loss].
AbstractHereditary hearing loss, with its well-defined molecular etiology, is a typical disease suitable for applying the concept of individualized precision medicine to clinical practice. Given its genetic heterogeneity and phenotypic diversity, there are particularities for the surgical treatment of hereditary hearing loss. Based on the results of the molecular epidemiological survey of large samples of deafness, various surgical methods and postoperative follow-up data, this expert consensus formulates a detailed guidance plan for the surgical treatment, efficacy evaluation and postoperative rehabilitation of hereditary hearing loss.
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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