DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hearing loss, autosomal dominant 87 — 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 87 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 87 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
phosphatidylinositol 4-kinase beta (PI4KB) — PI4KB 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 4-azanylcyclohexyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5FBR · 3.28 Å · ligand ~{N}-[2-[[3-[3-[(4-azanylcyclohexyl)sulfamoyl]-4-methoxy-phenyl]-6-chloranyl-2-methyl-imidazo[1,2-b]pyridazin-8-yl]amino]ethyl]ethanamide (5W7). 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. In a 2010 laboratory study, mutant cochlin, the protein product of the COCH gene, formed a stable dimer that was sensitive to reducing agent, whereas wild-type cochlin formed dimers only transiently. The presence of mutant cochlin stabilised wild-type cochlin in dimer conformation, and eventually induced wild-type cochlin to form stable oligomers resistant to reducing agent. Mutant cochlin was cytotoxic in vitro and in vivo. The study proposed a molecular mechanism involving protein misfolding and offered an in vitro model for exploring protein-misfolding diseases, but did not test any drug.
A 2001 case report described two patients with cleidocranial dysplasia, a rare autosomal dominant skeletal dysplasia, in whom hearing loss was the first presenting symptom. The authors emphasised the need for multidisciplinary evaluation of unexplained hearing loss to obtain a correct diagnosis for genetic counselling and management. A 2005 review noted that half of hearing loss causes have a genetic basis, and that existing treatment devices do not correct the underlying pathology. A 1995 review presented a pipeline model for genetic hearing loss research, from family identification through linkage analysis and gene sequencing to gene-based therapy, but noted that each mutation sits at a different point in the pipeline. A 2004 clinical study of 144 patients with nonsyndromic hearing loss described sex distribution, type, degree, symmetry, laterality, progression, aetiology, and inheritance pattern, but did not test any intervention. A 2000 report on a Brazilian family described a new autosomal-dominant non-progressive high-frequency sensorineural hearing loss first noted in early infancy, but again tested no drug.
No abstract in this set reports a drug tested for hearing loss, autosomal dominant 87 or any other genetic hearing loss. What is missing is any clinical trial, any drug repurposing screen, any animal model treated with a candidate compound, and any patient stratification by specific COCH mutation. Funding for preclinical drug testing in DFNA9 models, and a trial design that can measure change in a slowly progressive hearing loss, remain 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.
International Journal of Audiology · 1985 · 23 citations
Follow-Up Study in a Family with Dominant Progressive Hereditary Sensorineural Hearing Impairment II. Clinical Aspects
AbstractAn autosomal-dominant progressive sensorineural hearing loss in six generations of a large family with 105 affected members was studied. The pattern of inheritance is autosomal dominant with an almost complete penetrance. The age of onset is between 5 and 15 years. Individuals with a normal audiogram at the age of 15 and over will not develop the disorder. Different generations show an identical pattern of progression. Because the age of onset is the same, anticipation is excluded. The hearing loss is symmetrical. Over 40 years, low-frequency losses are greater in females than in males. Epistasis possibly plays a role since affected individuals in branch II of this family have a more severe expression than those in the other two affected branches. No abnormal excretion of organic acids in the urine could be established.Une atteinte auditive de perception héréditaire dominante a été étudiée dans une famille de six générations, 105 personnes atteintes. La transmission est autosomale dominante avec une pénétrance de presque 100%. L'anomalie débute entre 5 et 15 ans. Un individu de 15 ans ou plus avec un audiogramme normal ne sera jamais atteint de cette surdité. La progression dans les gënérations est identique et l'aˇge auquel se manifeste la maladie est le měme. La perte d'audition est symétrique pour l'oreille droite et gauche. La perte auditive sur les graves est plus importante chez les femmes que chez les hommes. Dans la branche généalogique II la perte d'audition se développe plus rapidement que dans les autres branches. L'excrétion urinaire d'acides organiques est normale.
Hearing Loss as a Presenting Symptom of Cleidocranial Dysplasia
AbstractOBJECTIVES: To report two cases of cleidocranial dysplasia in which hearing loss was the first presenting symptom. STUDY DESIGN: Retrospective case review. PATIENTS: Two cases of cleidocranial dysplasia, a rare autosomal dominant skeletal dysplasia affecting both membranous and enchondral bone formation. SETTING: Tertiary referral center. INTERVENTIONS: Clinical, audiometric, and imaging diagnostic procedures. CONCLUSION: With this report, we want to illustrate the possibility of a rare genetic disorder as the underlying cause of hearing loss. We also want to emphasize the need for a multidisciplinary approach and evaluation of unexplained hearing loss to obtain a correct diagnosis, which is important for genetic counseling and management of the patient and his or her family.
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.
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.
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.
American Journal of Medical Genetics · 2000 · 1 citations
?New? autosomal-dominant infantile sensorineural non-progressive high-frequency hearing loss: Report on a Brazilian family.
AbstractWe report on a three-generation Brazilian family with seven patients affected with non-progressive high-frequency sensorineural hearing loss with no associated anomalies first noted in early infancy. To our knowledge this is the first report on this autosomal-dominant condition. Clinical, audiological, and genetic aspects are discussed.
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.
