DeCure for Autosomal recessive nonsyndromic hearing loss 2
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal recessive nonsyndromic hearing loss 2 — 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 recessive nonsyndromic hearing loss 2 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 recessive nonsyndromic hearing loss 2 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 VIIA (MYO7A) — MYO7A 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 5MV9 · 2.6 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
The 1994 analysis of audiograms from 136 individuals across 28 families found that autosomal recessive nonsyndromic hearing loss was more severe than autosomal dominant loss, with residual and sharply sloping shapes predominating in the recessive group. Intrafamilial variation in degree of hearing loss was less marked in recessive families than in dominant ones. The authors concluded that audiograms are usually nonspecific and that counselling should be based on the specific family rather than group data.
A 2015 study of 3,864 Chinese individuals found that 106 (2.74%) carried a homozygous p.V37I mutation in GJB2 or a compound p.V37I plus another GJB2 pathogenic mutation, a frequency significantly higher than in 600 controls (0%). Hearing loss ranged from mild to profound, but 66.04% of these patients had mild or moderate hearing loss. The authors stated that the milder phenotype should be considered by otolaryngologists when this mutation is present.
A 2020 report on DFNB7/11 caused by TMC1 variants identified only 3 patients from 2 non-consanguineous families in a single Italian clinic. All had prelingual severe-to-profound hearing loss. After cochlear implantation, speech perception, nonverbal cognition, and speech performance were excellent and comparable to patients with DFNB1 deafness. The authors noted that their results do not support the variable auditory outcome reported elsewhere, which they attributed to social, environmental, and genetic factors.
What is still missing is large-scale prospective data on the natural history of specific recessive genotypes, particularly for the common GJB2 p.V37I variant, where the range of severity is wide and the proportion of patients who progress remains unclear. For TMC1-related deafness, the sample size is too small to draw firm conclusions about cochlear implant outcomes, and no drug intervention is mentioned in any of these abstracts. No trial design, patient stratification strategy, or funding source for a repurposing study is described.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Nonsyndromic Hearing Loss: An Analysis of Audiograms
AbstractWe examined features of the audiograms of 136 individuals, from 28 families, affected by nonsyndromic genetic hearing loss. There were 83 (12 families) with autosomal dominant (AD) loss, 50 (15 families) with autosomal recessive (AR) loss, and 3 (1 family) with X-linked recessive loss. The main audiogram shapes found were sloping (50.3%), residual (26.5%), and flat (21.0%). Specific shapes (ascending and U-shaped) only occurred in 3.7% of AD cases. Audiogram shapes were found to be significantly different between AD and AR families, and showed intrafamilial and interfamilial variability. In the AR group, the main shapes were residual and sharply sloping, and in the AD group, sharply sloping, flat, and gently sloping. There was a significant difference in the degree of hearing loss between AD and AR types, with AD being milder than AR. It has been shown that there is more marked intrafamilial variation in the degree of hearing loss in AD families than in AR ones. The results suggest that the audiograms of nonsyndromic hearing loss are usually nonspecific and that counseling of family members would be better based on the specific family's condition rather than on group information.
The Relationship between the p.V37I Mutation in GJB2 and Hearing Phenotypes in Chinese Individuals
AbstractThe most common cause of nonsyndromic autosomal recessive hearing loss is mutations in GJB2. The mutation spectrum and prevalence of mutations vary significantly among ethnic groups, and the relationship between p.V37I mutation in GJB2 and the hearing phenotype is controversial. Among the 3,864 patients in this study, 106 (2.74%) had a homozygous p.V37I variation or a compound p.V37I plus other GJB2 pathogenic mutation, a frequency that was significantly higher than that in the control group (600 individuals, 0%). The hearing loss phenotype ranged from mild to profound in all patients with the homozygous p.V37I variation or compound p.V37I plus other GJB2 pathogenic mutation. There was no difference in the distribution of the hearing level in the group with the homozygous p.V37I variation and the group with the compound p.V37I variation plus pathogenic mutation. Most patients (66.04%) with the V37I-homozygous variation or p.V37I plus other pathogenic mutation had a mild or moderate hearing level. This study found a definite relationship between p.V37I and deafness, and most patients who carried the pathogenic combination with p.V37I mutation had mild or moderate hearing loss. Therefore, otolaryngologists should consider that the milder phenotype might be caused by the GJB2 p.V37I mutation.
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.
Supplementary Material for: Auditory Outcome after Cochlear Implantation in Children with DFNB7/11 Caused by Pathogenic Variants in <b><i>TMC1</i></b> Gene
Abstract<b><i>Introduction:</i></b> Non-syndromic hereditary hearing loss is characterized by extreme genetic heterogeneity. So far, more than 100 pathogenic or likely pathogenic variants in <i>TMC1</i> gene have been reported in patients with autosomal recessive hearing loss (HL) DFNB7/11. The prevailing auditory phenotype of individuals with DFNB7/11 is congenital, profound, bilateral HL, but the functional outcome after cochlear implantation (CI) described in the literature is variable. The objective of this work is to evaluate the auditory outcome after CI in pediatric patients with DFNB7/11, born to non-consanguineous parents. <b><i>Methods:</i></b> A retrospective analysis of genetic and audiological data of DFNB7/11 patients followed up in a single Italian otolaryngology clinic was performed. Cases with biallelic pathogenic variants in <i>TMC1</i> were selected from the cohort of children with non-syndromic hearing loss who had undergone CI and had been molecularly characterized by multigene panel testing. All patients underwent extensive audiological assessment, and the auditory outcome after CI was evaluated. <b><i>Results:</i></b> DFNB7/11 was diagnosed in a total of 3 patients from 2 non-consanguineous families; a novel disease-causing variant in <i>TMC1</i> was detected [c.962G>A p.(Trp321*)]. All the affected children showed the typical DFNB7/11 phenotype characterized by prelingual, severe-to-profound HL. The patients showed an excellent functional outcome after CI; speech perception, nonverbal cognition, and speech performance were comparable to those of patients with DFNB1 deafness. <b><i>Discussion/Conclusion:</i></b> Our results do not support the variable auditory outcome reported in the literature, which may be affected by several social and environmental factors and by the genetic background.
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.
