DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hearing loss, autosomal dominant 86 — 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 86 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 86 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
THO complex subunit 1 (THOC1) — THOC1 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7ZNL · 3.45 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Mutations in the COCH gene cause DFNA9, an autosomal-dominant non-syndromic hearing loss disorder. Research from 2010 shows that mutant cochlin, the protein product of COCH, forms a stable dimer that is sensitive to reducing agent, whereas wild-type cochlin may form dimers only transiently. The presence of mutant cochlin can stabilise wild-type cochlin in dimer conformation, providing a possible mechanism for the dominant nature of DFNA9 mutations. Expression of mutant cochlin eventually induces wild-type cochlin to form stable oligomers that are resistant to reducing agent, and mutant cochlin is cytotoxic in vitro and in vivo. This suggests a protein-misfolding mechanism underlying DFNA9 hearing loss and provides an in vitro model that may be used to explore protein-misfolding diseases.
A 2025 observational study of 1651 patients aged 18 to 99 found that patients taking drugs, in both mono- and polytherapy regimens, had higher hearing deficits than patients not taking drugs. An apparent dose-response effect was observed, with the risk of moderate to severe impairment progressively increasing with the number of drugs taken. Drugs for cardiovascular diseases and drugs for acid-related disorders were significantly linked to an increased risk of perceived hearing impairment. Agents belonging to the antidiabetic category were associated with a potential protective effect. The cross-sectional design precludes inference of causality.
Epidemiological evidence from 2006 notes that genetic factors are major contributors to hearing loss, with many genes identified. Mutations in GJB2 explain a high proportion of genetic deafness in several populations. The majority of genetic hearing loss shows an autosomal recessive pattern, but autosomal dominant, X-linked, and mitochondrial forms exist. An estimated 50 to 80 hearing loss genes remain to be discovered, according to a 2000 review. A 2025 expert consensus on surgical treatment for hereditary hearing loss, based on molecular epidemiological survey results and postoperative follow-up data, formulates guidance for surgical treatment, efficacy evaluation and postoperative rehabilitation.
What is still missing is a therapy that targets the specific protein-misfolding mechanism of DFNA9. No drug has been tested in a clinical trial for this condition. The observational data on polypharmacy cannot establish whether drugs cause hearing loss or are merely associated with it. The large number of unidentified hearing-loss genes means that many patients cannot receive a molecular diagnosis, which is a prerequisite for any gene-specific intervention. Funding for preclinical development of a cochlin-stabilising or aggregation-inhibiting compound, and a trial design that can stratify patients by COCH mutation type, are 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.
Journal of Biological Chemistry · 2010 · 41 citations · open access
Role of Protein Misfolding in DFNA9 Hearing Loss
AbstractMutations in the COCH (coagulation factor C homology) gene have been attributed to DFNA9 (deafness, autosomal-dominant 9), an autosomal-dominant non-syndromic hearing loss disorder. However, the mechanisms responsible for DFNA9 hearing loss remain unknown. Here, we demonstrate that mutant cochlin, the protein product of the COCH gene, forms a stable dimer that is sensitive to reducing agent. In contrast, wild-type (WT) cochlin may form only dimers transiently. Interestingly, the presence of mutant cochlin can stabilize WT cochlin in dimer conformation, providing a possible mechanism for the dominant nature of DFNA9 mutations. Furthermore, the expression of mutant cochlin eventually induces WT cochlin to form stable oligomers that are resistant to reducing agent. Finally, we show that mutant cochlin is cytotoxic in vitro and in vivo. Our study suggests a possible molecular mechanism underlying DFNA9 hearing loss and provides an in vitro model that may be used to explore protein-misfolding diseases in general.
AbstractEpidemiological studies more than a century ago demonstrated that genetic factors are major contributors to hearing loss. Many genes associated with hearing loss have now been identified, although mutations in one of them, GJB2, explain a high proportion of genetic deafness in several populations. Environmental factors such as viruses (in particular, cytomegalovirus), ototoxic drugs, and noise also are associated with hearing loss, as is the aging process. Genetic hearing loss may be either syndromic (other organs and tissues are abnormal) or nonsyndromic. The majority show an autosomal recessive pattern of inheritance, but autosomal dominant, X-linked, and mitochondrial forms of hearing loss are found. In this article, four hearing loss syndromes, Jervell and Lange-Nielsen, Wolfram, branchio-otorenal, and Alport, are described; respectively, they are caused by mutations in genes encoding a potassium channel complex (KCNQ1, KCNE1), extracellular matrix proteins (COL4A3, COL4A4, COL4A5), transcription factors (EYA1, SIX1), and a protein that may be a novel endoplasmic reticulum calcium channel or a regulator of channel activity (WFS1). The contribution of mitochondrial DNA (mtDNA) mutations to hearing loss also is discussed.
Case Reports in Rheumatology · 2016 · 5 citations · open access
Rituximab Not Effective for Hearing Loss in Cogan’s Syndrome
AbstractImportance . Rituximab was not effective in ameliorating the hearing loss in a patient with atypical Cogan’s syndrome. Observations . We report the case of a patient who developed acute bilateral uveitis and sensorineural hearing loss. A diagnosis of atypical Cogan’s syndrome was made. The patient’s hearing loss did not improve despite high dose steroids and azathioprine. Rituximab was administered given a recent report of its efficacy in a patient with refractory disease; however, our patient’s hearing loss did not improve. Conclusion . Hearing loss in Cogan’s syndrome is difficult to treat. Though rituximab was ineffective in our case, earlier administration in the disease course could be effective for future patients.
Current Opinion in Otolaryngology & Head & Neck Surgery · 1995 · 2 citations
Modern clinical methods in genetic hearing loss
AbstractClinical methods in cases of genetic hearing loss have been influenced recently by both methodologic advances and specific findings made in the many research laboratories devoted to human genetic investigation. For the clinician, reports from these laboratories seem to suggest significant breakthroughs accompanied by allusions to clinical applicability. This review presents a rationale for the analysis of the many reports related to genetic hearing loss and their attending clinical impact. This rationale is based on a simplified view of the laboratory effort as a pipeline. A disease (mutation) passes through this pipeline on its way from family identification, through linkage analysis (chromosome localization), to gene sequencing and disease mechanism identification, and finally to gene-based therapy. Each stage of the investigation process has its own impact on clinical methods, and each mutation is in a particular spot in the pipeline at present. The pipeline itself is presented in this paper, along with the nature of the clinical impact of each level of laboratory findings.
[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.
Audiology Research · 2025 · 0 citations · open access
Association Between Polypharmacy and Self-Reported Hearing Disability: An Observational Study Using ATC Classification and HHIE-S-It Questionnaire
AbstractBACKGROUND: hearing loss represents, today, one of the most significant health problems affecting the world's population. This clinical condition, particularly manifest in adulthood, can arise or be aggravated by both the presence of specific pathologies and by taking multiple classes of drugs at the same time. METHODS: to understand this relationship, the present non-interventional observational study aimed to investigate the relationship between worsening hearing abilities in 1651 patients aged between 18 and 99 years. In particular, the thorough history of patients allowed us to evaluate the pathological profiles, pharmacological profiles, and therapeutic regimens adopted. This allowed us to evaluate its association with self-reported hearing loss, assessed through the administration of the HHIE-S-It questionnaire. Furthermore, given the presence of multimorbidity, the possible correlation between self-reported hearing loss and the specific classes of drugs, categorized using the Anatomical Therapeutic Classification (ATC) system, was evaluated. RESULTS: the results highlighted how patients taking drugs, both in mono- and polytherapy regimens, had higher hearing deficits than patients not taking drugs. Furthermore, an apparent dose-response effect, in which the risk of moderate to severe impairment progressively increased with the number of drugs taken, was also observed. Different classes of drugs, particularly those used for the treatment of diseases of the cardiovascular system, as well as drugs for acid-related disorders, were significantly linked to an increased risk of perceived hearing impairment. On the contrary, agents belonging to the antidiabetic category have proven to be drugs capable of offering a potential protective effect. CONCLUSION: this study highlighted how both the number of drugs taken and some specific categories of drugs can contribute to perceived hearing impairment. While this evidence highlights the importance of integrating audiological evaluation into the management of patients in polypharmacy, the cross-sectional nature of the design precludes the inference of causality. This evidence still favors safer and more personalized therapeutic strategies.
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.
