DeCure for Autosomal dominant nonsyndromic hearing loss 4A
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal dominant nonsyndromic hearing loss 4A — 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 moduleAutosomal dominant nonsyndromic hearing loss 4A 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 autosomal dominant nonsyndromic hearing loss 4a 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
myosin heavy chain 14 (MYH14) — MYH14 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 adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5JLH · 3.9 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
Hearing loss is the most common sensory defect in humans, affecting normal communication in 10 percent of people aged 65 years or older. Single-gene mutations can cause monogenic forms, which are either syndromic or nonsyndromic. Approximately 30 percent of genetically determined deafness is syndromic and 70 percent is nonsyndromic. Congenital hearing loss occurs in 1 in 1000 newborns. More than 400 genetic loci are associated with syndromic hearing loss and more than 100 with nonsyndromic hearing loss.
One Iranian family with two patients was studied. Whole exome sequencing identified a novel stop loss mutation, c.1048T>G (p.Term350Glu), within the P2RX2 gene. This mutation would cause continued translation into the 3' UTR, potentially producing a longer protein. The mutation segregated with the disease phenotype and was predicted pathogenic by bioinformatic tools. This was the first Iranian case report of autosomal dominant nonsyndromic hearing loss caused by a P2RX2 mutation.
The abstracts provide no data on survival, response rates, or any treatment intervention. No drug is mentioned in any of the abstracts. The evidence is limited to a single family with two patients, and the functional consequence of the mutation remains predicted rather than experimentally confirmed.
What is still missing: functional validation of the longer protein product, any animal or cellular model of the mutation, a larger patient cohort to establish the mutation’s prevalence, and any therapeutic strategy — drug or otherwise — that might target the P2RX2 pathway. No clinical trial, no repurposing candidate, and no patient stratification method have been proposed.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 2000 · 202 citations
Genetic Causes of Hearing Loss
AbstractHearing loss is the most common sensory defect in humans, affecting normal communication in 10 percent of people aged 65 years or older. In most cases, hearing loss is a multifactorial disorder caused by both genetic and environmental factors. However, single-gene mutations can lead to hearing loss. In these cases, hearing loss is a monogenic disorder with an autosomal dominant, autosomal recessive, X-linked, or mitochondrial mode of inheritance. These monogenic forms of hearing loss can be syndromic (characterized by hearing loss in combination with other abnormalities) or nonsyndromic (with only hearing loss). This review focuses on nonsyndromic hearing loss, since . . .
Current Opinion in Neurology · 1999 · 11 citations
Vestibular and hearing loss in genetic and metabolic disorders
AbstractHearing loss affects about 4% of people under 45 years of age and comprises a broad spectrum of clinical presentations (congenital or late-onset, conductive or sensorineural, and syndromic or nonsyndromic). Approximately 30% of genetically determined deafness is reported to occur in syndromic form and 70% in nonsyndromic form. This review highlights recent advances in the molecular and genetic basis of hearing loss, which will help in understanding the biology of normal and abnormal hearing.
Identification of a Novel Stop Loss Mutation in P2RX2 Gene in an Iranian Family with Autosomal Nonsyndromic Hearing Loss
AbstractBackground: Hearing loss, a congenital genetic disorder in human, is difficult to diagnose. Whole exome sequencing is a powerful approach for ethiological disgnosis of such disorders. Methods: One Iranian family with two patients were attented in the study. Sequencing of known non-syndromic hearing loss genes was carried out to recognize the genetic causes of HL. Results: Molecular analyses identified a novel stop loss mutation, c.1048T>G (p.Term350Glu), whitin the P2RX2 gene, causing a termination-site modification.This event would lead to continued translation into the 3' UTR of the gene, which in turn may result in a longer protein product. The mutation was segregating with the disease phenotype and predicted to be pathogenic by bioinformatic tools. Conclusion: This study is the first Iranian case report of a diagnosis of autosomal dominant nonsyndromic hearing loss (ADNSHL) caused by P2RX2 mutation. The recognition of other causative mutations in P2RX2 gene more supports the probable function of this gene in causing ADNSHL.
Medicinos teorija ir praktika · 2014 · 0 citations
Hereditary hearing loss. Genetic factors in ethiopathogenesis of deafness
AbstractCongenital hearing loss is one of the most common defects diagnosed 1 in 1000 newborns. Prelingual hearing loss disturbs development of the child and it is one of disabling conditions in present day environment. It is a highly heterogeneous disorder, with the majority of cases having genetic etiology. Ear is a very complex organ, proper development of the tissues in macroscopic, microscopic and molecular levels and function are essencial for the perception of sound. These processes are influenced mostly by genetic factors. Recent advances in the gene identification techniques have revolutionized the clinical approach to congenital hearing loss. More than 400 and 100 genetic loci are associated with syndromic and nonsyndromic hearing loss respectively. High heterogeneity of hearing loss is important in genetic counselling – the disorder may be inherited in autosomal dominant, autosomal recessive, X recessive and mitochondrial manner. In this review we discuss the structure and the function of auditory organ, the pathogenic mechanisms of hearing loss and provide the clinical approach. The identification of genes implicated in pathogenesis of hearing loss is essential in establishing of genetic diagnosis and rehabilitation, opens new perspectives in treatment, and allows predicting the severity of the disorder, progression and effectiveness of rehabilitating measures.
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.
