https://www.sciencedirect.com/science/article/abs/pii/S0361923018309183
Research
SENS-401 Effectively Reduces Severe Acoustic Trauma-Induced Hearing Loss in Male Rats
https://journals.lww.com/otology-neurotology/Abstract/2019/02000/SENS_401_Effectively_Reduces_Severe_Acoustic.29.aspx
https://www.ncbi.nlm.nih.gov/pubmed/30570608
SENS-401 Effectively Reduces Severe Acoustic Trauma-Induced Hearing Loss in Male Rats With Twice Daily Administration Delayed up to 96 hours
Abstract
HYPOTHESIS:
SENS-401 (R-azasetron besylate) is effective against severe acoustic trauma-induced hearing loss.
BACKGROUND:
SENS-401 has calcineurin inhibiting properties and attenuates cisplatin-induced hearing loss in a rat model. Cisplatin-induced and acoustic trauma-induced hearing loss share common apoptotic pathways.
METHODS:
The dose-response relationship of SENS-401 (6.6 mg/kg BID, 13.2 mg/kg BID, 26.4 mg/kg QD) and treatment time-window (13.2 mg/kg BID starting 24, 72, and 96 h posttrauma) versus placebo for 28 days were evaluated in a male rat model of severe acoustic trauma-induced hearing loss (120 dB SPL, 2 h) using auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) measures followed by cochlear outer hair cell (OHC) counting with myosin-VIIa immunolabeling.
RESULTS:
All SENS-401 doses improved ABR threshold shift and recovery, reaching statistical significance (p < 0.05) for ABR threshold recoveries after 28-days treatment. DPOAE amplitude loss and recovery improved markedly for 13.2 mg/kg BID SENS-401, reaching significance after 14 days (p < 0.05). Significant improvements in ABR threshold shifts/recovery and DPOAE amplitude loss occurred with up to 96-hours delay in initiating SENS-401 (p < 0.05), and in DPOAE amplitude recovery with up to 72-hours delay (p < 0.05). Significantly more surviving OHCs were present after SENS-401 treatment compared with placebo after 24 to 96-hours delay posttrauma, with up to 5.3-fold more cells in the basal cochlea turn.
CONCLUSIONS:
In vivo data support the otoprotective potential of twice daily oral SENS-401. Improvements in hearing loss recovery make SENS-401 a promising clinical candidate for acoustic trauma-induced hearing loss, including when treatment is not initiated immediately.
AAV2.7m8 is a powerful viral vector for inner ear gene therapy
https://www.nature.com/articles/s41467-018-08243-1
https://www.ncbi.nlm.nih.gov/pubmed/30683875
Treatment of military acoustic accidents with N-Acetyl-L-cysteine (NAC)
https://www.tandfonline.com/doi/abs/10.1080/14992027.2018.1543961?journalCode=iija20
https://pubmed.ncbi.nlm.nih.gov/30653365/
Treatment of military acoustic accidents with N-Acetyl-L-cysteine (NAC)
Ulf Rosenhall,Björn Skoog &Per Muhr
Pages 151-157 | Received 05 Mar 2018, Accepted 24 Oct 2018, Published online: 17 Jan 2019
Download citation https://doi.org/10.1080/14992027.2018.1543961
Targeting the downregulation of connexin30 (Cx30) in the cochlea might be a therapeutic option for the prevention of age-related hearing loss
https://jcs.biologists.org/content/132/2/jcs224097
https://www.ncbi.nlm.nih.gov/pubmed/30559251?dopt=Abstract
Targeting the downregulation of Cx30 in the cochlea might be a therapeutic option for the prevention of age-related hearing loss
Related Articles
The connexin 30 A88V mutant reduces cochlear gap junction expression and confers long-term protection against hearing loss.
J Cell Sci. 2019 01 16;132(2):
Authors: Kelly JJ, Abitbol JM, Hulme S, Press ER, Laird DW, Allman BL
Abstract
Mutations in the genes that encode the gap junction proteins connexin 26 (Cx26, encoded by GJB2) and Cx30 (GJB6) are the leading cause of hereditary hearing loss. That said, the Cx30 p.Ala88Val (A88V) mutant causes Clouston syndrome, but not hearing loss. Here, we report that the Cx30-A88V mutant, despite being toxic to inner ear-derived HEI-OC1 cells, conferred remarkable long-term protection against age-related high frequency hearing loss in Cx30A88V/A88V mice. During early development, there were no overt structural differences in the cochlea between genotypes, including a normal complement of hair cells; however, the supporting cell Cx30 gap junction plaques in mutant mice were reduced in size. In adulthood, Cx30A88V/A88V mutant mice had a reduction of cochlear Cx30 mRNA and protein, yet a full complement of hair cells. Conversely, the age-related high frequency hearing loss in Cx30+/+ and Cx30+/A88V mice was due to extensive loss of outer hair cells. Our data suggest that the Cx30-A88V mutant confers long-term hearing protection and prevention of hair cell death, possibly via a feedback mechanism that leads to the reduction of total Cx30 gap junction expression in the cochlea.
PMID: 30559251 [PubMed – indexed for MEDLINE]
Avocado Oil Extract (DKB122) Modulates Auditory Hair Cell Function through the Regulation of Amino Acid Biosynthesis Genes
https://www.mdpi.com/2072-6643/11/1/113
The Use of Gliatilin (Choline Alfoscerate) in Patients With Sensorineural Hearing Loss
https://pubmed.ncbi.nlm.nih.gov/32027336/
Gliatilin (Choline Alfoscerate)
Vestn Otorinolaringol
2019;84(6):132-136. doi: 10.17116/otorino201984061132.
[The Use of Gliathiline in Patients With Sensorineural Hearing Loss]
[Article in Russian]
N L Kunelskaya 1, E V Baybakova 2, E S Yanyushkina 2, M A Chugunova 2, M V Tardov 2, Z O Zaoeva 2, G N Izotova 2, E V Larionova 2
Affiliations collapse
Affiliations
1The Sverzhevskiy’s Research clinical Institute of Otorhinolaryngology, Moscow, Russia, 117152; Department of Otorhinolaryngology N.I. Pirogov Russian National Research Medical University, Moscow, Russia, 117997.
2The Sverzhevskiy’s Research clinical Institute of Otorhinolaryngology, Moscow, Russia, 117152.
PMID: 32027336 DOI: 10.17116/otorino201984061132
Abstract in English , Russian
The results of treatment of 38 patients suffering from sensorineural hearing loss with the Gliatilin (solution 3 ml intravenously for 10 days, capsules 400 mg 3 times a day or solution for ingestion 600 mg 2 times a day for 3 months) are presented. All patients in dynamics were given a comprehensive audiological, neurological examination, as well as an assessment of psycho-emotional status and cognitive function. Subjective improvement of ear noise tolerance by patients by 40 days of observation and continuation of this trend during the whole period (100 days) outside of the form of the medicinal preparation is noted. A reliable improvement in the 50% speech intelligibility threshold by day 100 of observation was established in patients of both groups, with a tendency towards earlier (on day 70 of the study) onset of this effect when taking the drug inside as a solution. The Gliatilin has been proven to reduce anxiety and depression, as well as reliably improve cognitive function. Thus, Gliatilin (injection solution, ingestion solution, capsules) can be used to improve the subjective tolerance of ear noise, speech intelligibility and quality of life of patients in chronic sensorineural hearing loss.
To hear a whisper: biotechs chase new thinking to restore hearing
https://www.nature.com/articles/nbt1218-1128
https://www.ncbi.nlm.nih.gov/pubmed/30520875?dopt=Abstract
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To hear a whisper: biotechs chase new thinking to restore hearing.
Nat Biotechnol. 2018 12 06;36(12):1128-1129
Authors: Jones D
PMID: 30520875 [PubMed – indexed for MEDLINE]
Tonotopy in calcium homeostasis and vulnerability of cochlear hair cells
https://www.sciencedirect.com/science/article/pii/S0378595518303940?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/30473131?dopt=Abstract
Related Articles
Tonotopy in calcium homeostasis and vulnerability of cochlear hair cells.
Hear Res. 2019 05;376:11-21
Authors: Fettiplace R, Nam JH
Abstract
Ototoxicity, noise overstimulation, or aging, can all produce hearing loss with similar properties, in which outer hair cells (OHCs), principally those at the high-frequency base of the cochlea, are preferentially affected. We suggest that the differential vulnerability may partly arise from differences in Ca2+ balance among cochlear locations. Homeostasis is determined by three factors: Ca2+ influx mainly via mechanotransducer (MET) channels; buffering by calcium-binding proteins and organelles like mitochondria; and extrusion by the plasma membrane CaATPase pump. We review quantification of these parameters and use our experimentally-determined values to model changes in cytoplasmic and mitochondrial Ca2+ during Ca2+ influx through the MET channels. We suggest that, in OHCs, there are two distinct micro-compartments for Ca2+ handling, one in the hair bundle and the other in the cell soma. One conclusion of the modeling is that there is a tonotopic gradient in the ability of OHCs to handle the Ca2+ load, which correlates with their vulnerability to environmental challenges. High-frequency basal OHCs are the most susceptible because they have much larger MET currents and have smaller dimensions than low-frequency apical OHCs.
PMID: 30473131 [PubMed – indexed for MEDLINE]
Generating inner ear organoids containing putative cochlear hair cells from human pluripotent stem cells
https://www.nature.com/articles/s41419-018-0967-1
https://www.ncbi.nlm.nih.gov/pubmed/30206231?dopt=Abstract
Related Articles
Generating inner ear organoids containing putative cochlear hair cells from human pluripotent stem cells.
Cell Death Dis. 2018 09 11;9(9):922
Authors: Jeong M, O’Reilly M, Kirkwood NK, Al-Aama J, Lako M, Kros CJ, Armstrong L
Abstract
In view of the prevalence of sensorineural hearing defects in an ageing population, the development of protocols to generate cochlear hair cells and their associated sensory neurons as tools to further our understanding of inner ear development are highly desirable. We report herein a robust protocol for the generation of both vestibular and cochlear hair cells from human pluripotent stem cells which represents an advance over currently available methods that have been reported to generate vestibular hair cells only. Generating otic organoids from human pluripotent stem cells using a three-dimensional culture system, we show formation of both types of sensory hair cells bearing stereociliary bundles with active mechano-sensory ion channels. These cells share many morphological characteristics with their in vivo counterparts during embryonic development of the cochlear and vestibular organs and moreover demonstrate electrophysiological activity detected through single-cell patch clamping. Collectively these data represent an advance in our ability to generate cells of an otic lineage and will be useful for building models of the sensory regions of the cochlea and vestibule.
PMID: 30206231 [PubMed – indexed for MEDLINE]
Association between Uncoupling Protein 2 Gene Ala55val Polymorphism and Sudden Sensorineural Hearing Loss
https://www.ncbi.nlm.nih.gov/pubmed/30100544?dopt=Abstract
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Association between Uncoupling Protein 2 Gene Ala55val Polymorphism and Sudden Sensorineural Hearing Loss.
J Int Adv Otol. 2018 Aug;14(2):166-169
Authors: Koide Y, Teranishi M, Sugiura S, Uchida Y, Nishio N, Kato K, Otake H, Yoshida T, Otsuka R, Ando F, Shimokata H, Hasegawa Y, Nakashima T, Sone M
Abstract
OBJECTIVES: The pathology of sudden sensorineural hearing loss, which is known as sudden deafness (SD), remains unknown. The purpose of this study was to investigate the association between mitochondrial uncoupling protein 2 (UCP2) polymorphism and SD risk.
MATERIALS AND METHODS: We compared 83 patients suffering from SD and 2048 controls who participated in the Longitudinal Study of Aging at the National Institute for Longevity Sciences. Multiple logistic regression was used to calculate the odds ratios (ORs) for SD with a polymorphism of the UCP2 (rs660339) gene.
RESULTS: Under the additive model of inheritance, UCP2 polymorphisms showed significant association with a SD risk. The OR was 1.468 (95% confidence interval, 1.056-2.040) with an adjustment for any past history, such as diabetes, dyslipidemia, or hypertension, and for age and sex.
CONCLUSION: Our results imply that the UCP2 (rs660339) polymorphism has a significant association with the risk of developing SD.
PMID: 30100544 [PubMed – indexed for MEDLINE]
Effects of parenteral papaverine and piracetam administration on cochlea following acoustic trauma
http://www.noiseandhealth.org/article.asp?issn=1463-1741;year=2018;volume=20;issue=93;spage=47;epage=52;aulast=Kum
https://www.ncbi.nlm.nih.gov/pubmed/29676295?dopt=Abstract
Related Articles
Effects of parenteral papaverine and piracetam administration on cochlea following acoustic trauma.
Noise Health. 2018 Mar-Apr;20(93):47-52
Authors: Kum NY, Yilmaz YF, Gurgen SG, Kum RO, Ozcan M, Unal A
Abstract
Introduction: Noise exposure, the main cause of hearing loss in countries with lot of industries, may result both in temporary or permanent hearing loss. The goal of this study was to investigate the effects of parenteral papaverine and piracetam administration following an acoustic trauma on hearing function with histopathologic correlation.
Materials and Methods: Eighteen Wistar albino rats exposed to noise for 8 h in a free environment were included. We divided the study population into three groups, and performed daily intraperitoneal injections of papaverine, piracetam, and saline, respectively, throughout the study. We investigated the histopathologic effects of cellular apoptosis on inner hair cells (IHCs) and outer hair cells (OHCs) and compared the distortion product otoacoustic emissions (DPOAEs) thresholds among the groups.
Results and Discussion: On the 3rd and 7th days, DPOAE thresholds at 8 kHz were significantly higher both in papaverine and piracetam groups compared with the control group (P = 0.004 for 3rd day, P = 0.016 and P = 0.028 for 7th day, respectively). On the 14th day, piracetam group had significantly higher mean thresholds at 8 kHz (P = 0.029); however, papaverine group had similar mean thresholds compared to the control group (P = 0.200). On the 3rd and 7th days following acoustic trauma, both IHC and OHC loss were significantly lower in both papaverine and piracetam groups. On the 7th day, the mean amount of apoptotic IHCs and OHCs identified using Caspase-3 method were significantly lower in both groups, but the mean amount identified using terminal deoxynucleotidyl transferase dUTP nick end labeling method were similar in both groups compared to the control group.
Conclusion: We demonstrated the effects of papaverine and piracetam on the recovery of cochlear damage due to acoustic trauma on experimental animals using histopathologic and electrophysiologic examinations.
PMID: 29676295 [PubMed – indexed for MEDLINE]