DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for deafness, aminoglycoside-induced — 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 moduleDeafness, aminoglycoside-induced 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 deafness, aminoglycoside-induced 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.
What the evidence adds up to
A 2010 study of 40 CAPD patients found that those treated with intraperitoneal aminoglycosides for peritonitis had significantly higher hearing thresholds at both low and high frequencies compared to patients who never had peritonitis (p=0.001 and p=0.007). The severity of hearing loss ranged from mild to profound deafness, and a correlation existed between the severity and the total cumulative aminoglycoside dose. A 2015 review states that aminoglycoside-induced hearing loss is permanent and negatively affects quality of life, though it notes that timely intervention can minimise the impact on daily life. The review discusses predisposing factors and the management of cochlear ototoxicity.
A 2024 commentary estimates that preventable hearing loss from anti-infective therapies accounts for 32.4 million cases per year globally. It notes that ototoxicity monitoring is often neglected, especially in cystic fibrosis patients and in low- and middle-income countries where audiology services are scarce. For multidrug-resistant tuberculosis, the commentary states that aminoglycosides had only modest activity and are being replaced by newer WHO regimens. However, for non-tuberculous mycobacteria (NTM) infections, guideline-based treatment still frequently relies on prolonged aminoglycoside use, and global NTM rates have increased, with pulmonary NTM incidence rising from 3.13 to 4.73 per 100,000 person-years between 2008 and 2015.
The 2024 commentary reports that treatment outcomes for NTM are usually poor, and actual success rates are unclear because aminoglycoside doses are reduced or stopped when clinically significant ototoxicity occurs, undermining cure rates. A 2023 survey of 73 doctors found that 64% would stop aminoglycosides if a patient reported ototoxicity, even when the drug was believed essential. The commentary calls for improved audiology services, including portable digital screening, and for further development of otoprotectants. What remains missing is reliable global incidence data for NTM, routine audiological testing before and during aminoglycoside treatment, and clinical trials of otoprotective agents that could allow full-dose therapy to be completed.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
South African Family Practice · 2015 · 63 citations · open access
Aminoglycoside-induced hearing deficits – a review of cochlear ototoxicity
AbstractThis article aims to inform the reader about current knowledge of the effects of aminoglycosides on hearing. The hearing loss caused by aminoglycosides is permanent and can negatively affect the individual’s quality of life. Although treatment with aminoglycosides cannot be avoided in some instances, timely intervention can minimise the impact of the hearing loss on the individual’s everyday life. The discussion includes the incidence of aminoglycoside-induced hearing loss and predisposing factors. In addition, monitoring and management of cochlear ototoxicity is described.
Correlation between Hearing Loss and Peritonitis Frequency and Administration of Ototoxic Intraperitoneal Antibiotics in Patients with CAPD
AbstractAIM: Aminoglycosides have been used in the treatment of CAPD peritonitis despite their potential risk for ototoxicity. The ototoxicity risk of intraperitoneally administered aminoglycosides has been investigated by a number of studies. However, their results are somewhat conflicting. The aim of the present study was to examine the frequency of hearing loss and the correlation between the repeated doses of aminoglycosides and hearing loss in CAPD peritonitis therapy. METHODS: Hearing functions of the CAPD patients who had developed peritonitis and had been treated with various antibiotics including aminoglycosides were compared with those CAPD patients who had never developed peritonitis. Threshold values for hearing were determined through "pure tone audiometry" measurements. RESULTS: Hearing threshold levels of the patients with history of peritonitis were found to be significantly higher in both lower [pure tone averages - 1 (PTA-1)] and higher [pure tone averages - 2 (PTA-2)] frequencies, when compared to the ones with no history of peritonitis (p values were 0.001 and 0.007, respectively). CONCLUSION: The present study showed that intraperitoneal aminoglycoside administration in CAPD patients is associated with the development of hearing loss. The severity of hearing loss may range from mild hearing loss to profound deafness. A remarkable correlation exists between the severity of the hearing loss and the repeated and total aminoglycoside dose received.
International Journal of General Medicine · 2021 · 11 citations · open access
Clinical Analysis of Intratympanic Injection of Dexamethasone for Treating Sudden Deafness
AbstractINTRODUCTION: A variety of causes may induce sudden deafness. However, it remains challenging to determine the exact cause in a clinic. There is no standard treatment for this disease due to its unclear etiology. OBJECTIVE: The present study aims to investigate the clinical efficacy of the intratympanic injection of dexamethasone for treating sudden deafness. METHODS: A total of 154 patients with sudden deafness were retrospectively analyzed. The evaluation of sudden deafness was based on the AAO-HNS efficacy evaluative criteria. All patients were initially treated within seven days by an intravenous drip of methylprednisolone, vasodilator, and neurotrophic agents. These patients were divided into two groups: the treatment group (91 patients) and the control group (63 patients). Patients in the treatment group were given an intratympanic injection of dexamethasone, while patients in the control group were given conventional vasodilators and neurotrophic treatment. RESULTS: The effective rate in the treatment group was 47.25% (43/91 patients), and this was significantly higher than in the control group (14.29%, 9/63 patients). The adverse reactions in the treatment group included transient pain (7.69%, 7/91), but there was no vertigo in either group. There was one case of tympanic membrane perforation. CONCLUSION: The intratympanic injection of dexamethasone is a better choice for refractory sudden deafness due to its high efficacy and fewer adverse reactions.
The Lancet Global Health · 2024 · 2 citations · open access
Aminoglycosides, deafness, and non-tuberculous mycobacteria
AbstractKavita Prasad and colleagues’ study1Prasad K Borre ED Dillard LK et al.Priorities for hearing loss prevention and estimates of global cause-specific burdens of hearing loss: a systematic rapid review.Lancet Glob Health. 2024; 12: e217-e225Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar addressing the global burden of deafness is very timely, particularly preventable causes related to anti-infective therapies (32·4 million cases per annum). Appropriate aminoglycoside prescribing is essential for individual clinical benefit, to reduce ototoxicity and, more broadly, to reduce the development of antimicrobial resistance. Ototoxicity monitoring is often neglected when aminoglycosides are used. This is especially true in specific populations, such as those with cystic fibrosis and in low-income and middle-income countries, where audiology services are scarce, making early diagnosis of hearing loss difficult. At least for multidrug-resistant tuberculosis therapy, aminoglycoside use should decline as recent studies showed that aminoglycosides had only modest activity against multidrug-resistant tuberculosis and are being replaced by newer WHO-recommended treatment regimens.2WHOWHO operational handbook on tuberculosis. Module 4: treatment—drug-resistant tuberculosis treatment, 2022 update. World Health Organization, Geneva2022Google Scholar However, one relevant and related group of infections, not considered in the study were those caused by non-tuberculous mycobacteria. This is due to a scarcity of reliable data for incidence and outcomes because there is usually no mandatory reporting of non-tuberculous mycobacteria, unlike tuberculosis, and most laboratories in low-income and middle-income countries are unable to identify non-tuberculous mycobacteria. Nevertheless, global rates of non-tuberculous mycobacteria have increased drastically. Annual incidence of pulmonary non-tuberculous mycobacteria disease increased from 3·13 to 4·73 per 100 000 person-years between 2008 and 2015, with an average increase in yearly incidence of 5·2%.3Seddon P Fidler K Raman S et al.Prevalence of nontuberculous mycobacteria in cystic fibrosis clinics, United Kingdom, 2009.Emerg Infect Dis. 2013; 19: 1128-1130Crossref PubMed Scopus (41) Google Scholar, 4Bhanushali J Jadhav U Ghewade B Wagh P Unveiling the clinical diversity in nontuberculous mycobacteria (NTM) infections: a comprehensive review.Cureus. 2023; 15e48270Google Scholar Guideline-based treatment of non-tuberculous mycobacteria frequently relies on prolonged use of aminoglycosides.5Daley CL Iaccarino JM Lange C et al.Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline.Clin Infect Dis. 2020; 71: 905-913Crossref PubMed Scopus (261) Google Scholar Despite mandating audiological testing, this is not always done before aminoglycoside treatment begins and often testing is done only when the patient has clinical symptoms. There is frequently a shortage of audiology capacity or reduced access, as occurred during the COVID-19 pandemic. Estimates of treatment outcomes for non-tuberculous mycobacteria are usually poor5Daley CL Iaccarino JM Lange C et al.Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline.Clin Infect Dis. 2020; 71: 905-913Crossref PubMed Scopus (261) Google Scholar but, in practice, the actual success rates are unclear because aminoglycoside doses are reduced or stopped when clinically significant ototoxicity occurs, undermining cure rates. In 2023, we did a survey of doctors who were members of the European Society for Clinical Microbiology and Infectious Diseases Mycobacterial Sub-Group and found that although 62 (85%) of 73 respondents followed national or international treatment guidelines for non-tuberculous mycobacteria, including the use of aminoglycosides, 47 (64%) of 73 would stop aminoglycosides if ototoxicity was reported by the patient, even when it was believed to be an essential drug.5Daley CL Iaccarino JM Lange C et al.Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline.Clin Infect Dis. 2020; 71: 905-913Crossref PubMed Scopus (261) Google Scholar If we are to truly understand optimal aminoglycoside therapy, we need to improve audiology services, including implementation of portable digital audiology screening methods6Vijayasingam A Frost E Wilkins J et al.Tablet and web-based audiometry to screen for hearing loss in adults with cystic fibrosis.Thorax. 2020; 75: 632-639Crossref PubMed Scopus (12) Google Scholar and consider the use and further development of otoprotectants to reduce hearing loss. We declare no competing interests. Priorities for hearing loss prevention and estimates of global cause-specific burdens of hearing loss: a systematic rapid reviewThe global burden of preventable hearing loss is large. Hearing loss that is attributable to disease sequelae or ototoxic medications contributes substantially to the global burden of hearing loss. Prevention of these conditions should be a global health priority. Full-Text PDF Open Access
South African Family Practice · 2015 · 0 citations · open access
Aminoglycoside-induced hearing deficits – a review of cochlear ototoxicity
AbstractThis article aims to inform the reader about current knowledge of the effects of aminoglycosides on hearing. The hearing loss caused by aminoglycosides is permanent and can negatively affect the individual’s quality of life. Although treatment with aminoglycosides cannot be avoided in some instances, timely intervention can minimise the impact of the hearing loss on the individual’s everyday life. The discussion includes the incidence of aminoglycoside-induced hearing loss and predisposing factors. In addition, monitoring and management of cochlear ototoxicity is described. (Full text available online at www.medpharm.tandfonline.com/ojfp) S Afr Fam Pract 2015; DOI: 10.1080/20786190.2014.1002220
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.
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