Studies on the Toxicity of Streptomycin for Man: A Preliminary Report

Hettig, Robert A.; Adcock, John D.

doi:10.1126/science.103.2673.355

Cited by 26 publications

(6 citation statements)

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“…aminoglycosides and clitocine) or not effective enough to offer sufficient therapeutic benefits (e.g. ataluren) 32,[56][57][58] . New molecules are being developed to address all these issues, such as an ataluren derivative named PTC414, more effective than ataluren 59 , and new-generation aminoglycosides 25,60,61 , designed to increase the efficiency of readthrough correction and decrease the long-term toxicity associated with the previous generation.…”

Section: Discussionmentioning

confidence: 99%

2,6-Diaminopurine as a highly potent corrector of UGA nonsense mutations

et al. 2020

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Nonsense mutations cause about 10% of genetic disease cases, and no treatments are available. Nonsense mutations can be corrected by molecules with nonsense mutation readthrough activity. An extract of the mushroom Lepista inversa has recently shown highefficiency correction of UGA and UAA nonsense mutations. One active constituent of this extract is 2,6-diaminopurine (DAP). In Calu-6 cancer cells, in which TP53 gene has a UGA nonsense mutation, DAP treatment increases p53 level. It also decreases the growth of tumors arising from Calu-6 cells injected into immunodeficient nude mice. DAP acts by interfering with the activity of a tRNA-specific 2′-O-methyltransferase (FTSJ1) responsible for cytosine 34 modification in tRNA Trp. Low-toxicity and high-efficiency UGA nonsense mutation correction make DAP a good candidate for the development of treatments for genetic diseases caused by nonsense mutations.

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Section: Discussionmentioning

confidence: 99%

2,6-Diaminopurine as a highly potent corrector of UGA nonsense mutations

et al. 2020

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“…While AGs preferentially target the bacterial ribosome, the inner ear and kidney are known to receive collateral damage in many patients receiving treatment [ 11 , 12 ]. However, a meta-analysis comparing once versus multiple-daily regimens of different AGs could not determine a statistical significant correlation between ototoxicity and treatment regimens [ 60 ].…”

Section: Ototoxicity and Mechanism Of Hair Cell Damagementioning

confidence: 99%

“…While damage inflicted by AG on the kidney is usually reversible [ 8 , 9 ], damage to the inner ear is permanent [ 10 ]. This nephro- and ototoxicity was initially discovered in the first clinical trials of streptomycin [ 11 , 12 ]. Within the inner ear, streptomycin preferably damages the vestibular organ [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection

Huth

Ricci

Cheng

2011

International Journal of Otolaryngology

324

302

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Aminoglycosides are commonly prescribed antibiotics with deleterious side effects to the inner ear. Due to their popular application as a result of their potent antimicrobial activities, many efforts have been undertaken to prevent aminoglycoside ototoxicity. Over the years, understanding of the antimicrobial as well as ototoxic mechanisms of aminoglycosides has increased. These mechanisms are reviewed in regard to established and potential future targets of hair cell protection.

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“…Although aminoglycosides show the capacity to elicit PTC readthrough, the clinical development of aminoglycosides was stopped because of evidence of irreversible ototoxicity and reversible nephrotoxicity after long exposures [ 28 , 29 , 30 , 31 , 32 , 33 ]. Since then, less toxic aminoglycoside derivatives and non-aminoglycoside molecules have been tested.…”

Section: Introductionmentioning

confidence: 99%

Optimized approach for the identification of highly efficient correctors of nonsense mutations in human diseases

et al. 2017

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About 10% of patients with a genetic disease carry a nonsense mutation causing their pathology. A strategy for correcting nonsense mutations is premature termination codon (PTC) readthrough, i.e. incorporation of an amino acid at the PTC position during translation. PTC-readthrough-activating molecules appear as promising therapeutic tools for these patients. Unfortunately, the molecules shown to induce PTC readthrough show low efficacy, probably because the mRNAs carrying a nonsense mutation are scarce, as they are also substrates of the quality control mechanism called nonsense-mediated mRNA decay (NMD). The screening systems previously developed to identify readthrough-promoting molecules used cDNA constructs encoding mRNAs immune to NMD. As the molecules identified were not selected for the ability to correct nonsense mutations on NMD-prone PTC-mRNAs, they could be unsuitable for the context of nonsense-mutation-linked human pathologies. Here, a screening system based on an NMD-prone mRNA is described. It should be suitable for identifying molecules capable of efficiently rescuing the expression of human genes harboring a nonsense mutation. This system should favor the discovery of candidate drugs for treating genetic diseases caused by nonsense mutations. One hit selected with this screening system is presented and validated on cells from three cystic fibrosis patients.

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Studies on the Toxicity of Streptomycin for Man: A Preliminary Report

Cited by 26 publications

References 1 publication

2,6-Diaminopurine as a highly potent corrector of UGA nonsense mutations

2,6-Diaminopurine as a highly potent corrector of UGA nonsense mutations

Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection

Optimized approach for the identification of highly efficient correctors of nonsense mutations in human diseases

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