Ototoxicity is an unwanted exposure to the pharmaceutical or environmental agents that damage the sensory and non-sensory cells of the inner ear, leading to hearing and balance impairment. Pharmaceutical drugs that cause hearing loss (HL) and/or balance disorders (BD) are widely known as ototoxic drugs. The detrimental effects of ototoxic drugs are largely described in the sensory hair cells (HCs) of the cochlea and vestibular tissues, and spiral ganglion neurons (SGn). Many ototoxic agents such as antibiotics, platinum-based drugs, loop diuretics and antimalarial drugs are commonly used in clinics due to its effectiveness against multiple microbial infections and other disease conditions in children and adults. In addition, commonly used non-steroidal anti-inflammatory drugs like aspirin and ibuprofen can cause tinnitus and HL when administered at high doses. Other ototoxic chemicals including organometals (such as mercury and organotins), and solvents (such as styrene and toluene) used in industrial settings, put industrial worker at higher risk of HL and BD. Industrial workers are also often exposed to loud noise which is another major cause of hearing impairment. Similarly, patients undergoing cisplatin chemotherapy for Head and Neck cancer also receive radiotherapy which can exacerbate the Cisplatin mediated HL. Currently there is no FDA approved drug or cell-based therapy available for the treatment of any form of hearing loss and balance disorders.
Over the past few decades, ototoxic effects of antibiotics like aminoglycosides and platinum-based drugs like cisplatin have been extensively studied in varieties of experimental models. Although, aminoglycosides and cisplatin have different mechanism(s) of action at cellular and molecular level, multiple studies have suggested that they share some common signaling pathways involving inflammation and ROS generation resulting in induction of apoptosis in HC and SGn. Various studies have targeted these molecular pathways to demonstrate otoprotective effects of antioxidants and anti-inflammatory agents in experimental models. Yet, our current understanding of HC survival and neuronal innervation after ototoxic insults in mammals remain limited, and the molecules that demonstrated translational potential in the pre-clinical studies, either never made it to clinical trials or failed to show efficacy in the clinics. The only molecule to show some efficacy in clinical trials is intravenous injection of Sodium thiosulfate (STS) against cisplatin-induced HL in cancer patients. However, binding of STS inactivates cisplatin and due to same route of administration of these two drugs, STS compromised the chemotherapeutic ability of cisplatin leading to increased mortality in a phase III clinical trial. This suggests that even though certain basic research findings hold great promises for effective otoprotection, there is a substantial knowledge gap that restrains the translation potentials of such otoprotective modalities. Therefore, further careful investigations in the experimental models are warranted before proceeding to large scale clinical trials.
This Research Topic welcomes Original Research and Review Articles related to, but not limited to:
- Novel mechanisms and different models of ototoxic injuries
- Novel targets to prevent or alleviate ototoxicity
- Gene and cell-based therapy for ototoxic HL and BD in animal models
- Studies understanding the combinatorial effect of two or more causes of HL.
- Studies providing insights into the challenges associated with deciphering mechanisms contributing to ototoxicity, diagnosis and clinical trials.
- This effort could tremendously help in improving our knowledge of ototoxicity and develop clinically relevant therapies.
Note - The cover image shows hair cells labeled with Myosin VIIa antibody (red) and neurons labeled with Neurofilament +Tuj1 antibodies (blue) in the neonatal mouse cochlea.
Credit: Dr. Vikrant Borse, Washington University in Saint Louis.
We would like to acknowledge Dr. Sumana Ghosh from University of Mississippi, Medical Centre (Jackson, MS) for her contribution in the development of this research topic theme.
Dr. Pranav Mathur is currently employed at Otonomy which works towards the development of new treatment options for hearing and balance disorders
Ototoxicity is an unwanted exposure to the pharmaceutical or environmental agents that damage the sensory and non-sensory cells of the inner ear, leading to hearing and balance impairment. Pharmaceutical drugs that cause hearing loss (HL) and/or balance disorders (BD) are widely known as ototoxic drugs. The detrimental effects of ototoxic drugs are largely described in the sensory hair cells (HCs) of the cochlea and vestibular tissues, and spiral ganglion neurons (SGn). Many ototoxic agents such as antibiotics, platinum-based drugs, loop diuretics and antimalarial drugs are commonly used in clinics due to its effectiveness against multiple microbial infections and other disease conditions in children and adults. In addition, commonly used non-steroidal anti-inflammatory drugs like aspirin and ibuprofen can cause tinnitus and HL when administered at high doses. Other ototoxic chemicals including organometals (such as mercury and organotins), and solvents (such as styrene and toluene) used in industrial settings, put industrial worker at higher risk of HL and BD. Industrial workers are also often exposed to loud noise which is another major cause of hearing impairment. Similarly, patients undergoing cisplatin chemotherapy for Head and Neck cancer also receive radiotherapy which can exacerbate the Cisplatin mediated HL. Currently there is no FDA approved drug or cell-based therapy available for the treatment of any form of hearing loss and balance disorders.
Over the past few decades, ototoxic effects of antibiotics like aminoglycosides and platinum-based drugs like cisplatin have been extensively studied in varieties of experimental models. Although, aminoglycosides and cisplatin have different mechanism(s) of action at cellular and molecular level, multiple studies have suggested that they share some common signaling pathways involving inflammation and ROS generation resulting in induction of apoptosis in HC and SGn. Various studies have targeted these molecular pathways to demonstrate otoprotective effects of antioxidants and anti-inflammatory agents in experimental models. Yet, our current understanding of HC survival and neuronal innervation after ototoxic insults in mammals remain limited, and the molecules that demonstrated translational potential in the pre-clinical studies, either never made it to clinical trials or failed to show efficacy in the clinics. The only molecule to show some efficacy in clinical trials is intravenous injection of Sodium thiosulfate (STS) against cisplatin-induced HL in cancer patients. However, binding of STS inactivates cisplatin and due to same route of administration of these two drugs, STS compromised the chemotherapeutic ability of cisplatin leading to increased mortality in a phase III clinical trial. This suggests that even though certain basic research findings hold great promises for effective otoprotection, there is a substantial knowledge gap that restrains the translation potentials of such otoprotective modalities. Therefore, further careful investigations in the experimental models are warranted before proceeding to large scale clinical trials.
This Research Topic welcomes Original Research and Review Articles related to, but not limited to:
- Novel mechanisms and different models of ototoxic injuries
- Novel targets to prevent or alleviate ototoxicity
- Gene and cell-based therapy for ototoxic HL and BD in animal models
- Studies understanding the combinatorial effect of two or more causes of HL.
- Studies providing insights into the challenges associated with deciphering mechanisms contributing to ototoxicity, diagnosis and clinical trials.
- This effort could tremendously help in improving our knowledge of ototoxicity and develop clinically relevant therapies.
Note - The cover image shows hair cells labeled with Myosin VIIa antibody (red) and neurons labeled with Neurofilament +Tuj1 antibodies (blue) in the neonatal mouse cochlea.
Credit: Dr. Vikrant Borse, Washington University in Saint Louis.
We would like to acknowledge Dr. Sumana Ghosh from University of Mississippi, Medical Centre (Jackson, MS) for her contribution in the development of this research topic theme.
Dr. Pranav Mathur is currently employed at Otonomy which works towards the development of new treatment options for hearing and balance disorders
