DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hearing loss, autosomal dominant 75 — 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 75 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 75 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
transformation/transcription domain associated protein (TRRAP) — TRRAP 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 ihpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9CAD · 3.05 Å · ligand INOSITOL HEXAKISPHOSPHATE (IHP). Experimental structure, not a prediction.
What the evidence adds up to
No drug is tested or proposed for DFNA9 in any of the provided abstracts. The 2010 study on DFNA9 shows that mutations in the COCH gene cause the mutant cochlin protein to form stable dimers and eventually force wild-type cochlin into stable, reducing-agent-resistant oligomers. Mutant cochlin is cytotoxic in vitro and in vivo. The authors propose this as a protein-misfolding mechanism for the dominant inheritance pattern, but they offer no intervention. The 2021 review confirms that no federally approved drug exists to prevent or treat any form of drug-induced hearing loss, let alone genetic hearing loss. The 2025 observational study of 1651 patients found that polypharmacy is associated with worse self-reported hearing, with a dose-response effect, and that cardiovascular drugs and acid-related disorder drugs were linked to increased risk, while antidiabetic agents showed a potential protective association. That study explicitly states its cross-sectional design precludes any inference of causality.
The 2004 clinical genetic study of 144 patients with nonsyndromic hearing loss describes sex distribution, type, degree, symmetry, laterality, progression, and inheritance pattern but does not test any drug. The 1991 abstract (title in Spanish) notes that whole-exome sequencing cannot achieve a 100% diagnostic rate in genetically heterogeneous hearing loss. The 2000 German-language paper reports that 11 genes for autosomal dominant hearing loss and 6 for autosomal recessive hearing loss had been isolated at that time, with an estimated 50 to 80 hearing loss genes still undiscovered.
What is missing for DFNA9 specifically: no drug has been tested in any animal model or human trial for this mutation. The protein-misfolding mechanism described in 2010 has not been translated into a therapeutic strategy. No funding for a repurposing screen, no clinical trial design, and no patient stratification by COCH mutation type exist in these abstracts. The broader field of hearing loss drug development lacks any approved therapy, and the observational polypharmacy data cannot guide treatment for a monogenic disorder.
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 · 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.
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.
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.
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.
AbstractOur findings confirm the complex genetic landscape of hearing loss and the limitations of WES in achieving a 100% diagnostic rate, especially in conditions characterized by genetic heterogeneity. These results contribute to our understanding of the genetic basis of hearing loss and emphasize the need for further research and comprehensive genetic analyses to elucidate the underlying causes of this condition.
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.
International Journal of Human Genetics · 2004 · 0 citations
Earpits Syndrome in Children with Hearing Loss
AbstractEarpits syndrome is a very rare kind of syndrome deafness and inherited as autosomal dominant. A study was taken up to understand the prevalence of this syndrome in children below the age of 14 years with hearing loss. Out of 743 children with hearing impairment, earpits syndrome was observed in 2(0.27%) cases. Both the children were the products of consanguineous marriage. Mixed hearing loss was noticed in one case and conductive hearing loss in another case. However, no renal anomalies were detected in either of these cases.
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.
