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CATEGORY:
Research

SCREENSHOT:

TITLE:
Potential role of Bcl2 in lipid metabolism and synaptic dysfunction of age-related hearing loss

CONTENT:
Neurobiol Dis. 2023 Oct 7:106320. doi: 10.1016/j.nbd.2023.106320. Online ahead of print.

ABSTRACT

Age-related hearing loss (ARHL) is a prevalent condition affecting millions of individuals globally. This study investigated the role of the cell survival regulator Bcl2 in ARHL through in vitro and in vivo experiments and metabolomics analysis. The results showed that the lack of Bcl2 in the auditory cortex affects lipid metabolism, resulting in reduced synaptic function and neurodegeneration. Immunohistochemical analysis demonstrated enrichment of Bcl2 in specific areas of the auditory cortex, including the secondary auditory cortex, dorsal and ventral areas, and primary somatosensory cortex. In ARHL rats, a significant decrease in Bcl2 expression was observed in these areas. RNAseq analysis showed that the downregulation of Bcl2 altered lipid metabolism pathways within the auditory pathway, which was further confirmed by metabolomics analysis. These results suggest that Bcl2 plays a crucial role in regulating lipid metabolism, synaptic function, and neurodegeneration in ARHL; thereby, it could be a potential therapeutic target. We also revealed that Bcl2 probably has a close connection with lipid peroxidation and reactive oxygen species (ROS) production occurring in cochlear hair cells and cortical neurons in ARHL. The study also identified changes in hair cells, spiral ganglion cells, and nerve fiber density as consequences of Bcl2 deficiency, which could potentially contribute to the inner ear nerve blockage and subsequent hearing loss. Therefore, targeting Bcl2 may be a promising potential therapeutic intervention for ARHL. These findings provide valuable insights into the molecular mechanisms underlying ARHL and may pave the way for novel treatment approaches for this prevalent age-related disorder.

PMID:37813166 | DOI:10.1016/j.nbd.2023.106320

SOURCE:
Neurobiology of disease

PUBLISHER:

PMID:
pubmed:37813166

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:37813166

DOI:
10.1016/j.nbd.2023.106320

DATE – PUBLISHED:
Mon, 09 Oct 2023 06:00:00 -0400

DATE – DOI:
2023-10-07T15:28:04Z

DATE – ADDED:
10/10/23 12:37AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37813166/

LINK – DOI:
https://doi.org/10.1016/j.nbd.2023.106320

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S0969996123003364?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-10-10T04:37:57+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Intranasal delivery of NGF rescues hearing impairment in aged SAMP8 mice

CONTENT:
Cell Death Dis. 2023 Sep 13;14(9):605. doi: 10.1038/s41419-023-06100-8.

ABSTRACT

Hearing loss impacts the quality of life and affects communication resulting in social isolation and reduced well-being. Despite its impact on society and economy, no therapies for age-related hearing loss are available so far. Loss of mechanosensory hair cells of the cochlea is a common event of hearing loss in humans. Studies performed in birds demonstrating that they can be replaced following the proliferation and transdifferentiation of supporting cells, strongly pointed out on HCs regeneration as the main focus of research aimed at hearing regeneration. Neurotrophins are growth factors involved in neuronal survival, development, differentiation, and plasticity. NGF has been involved in the interplay between auditory receptors and efferent innervation in the cochlea during development. During embryo development, both NGF and its receptors are highly expressed in the inner ears. It has been reported that NGF is implicated in the differentiation of auditory gangliar and hair cells. Thus, it has been proposed that NGF administration can decrease neuronal damage and prevent hearing loss. The main obstacle to the development of hearing impairment therapy is that efficient means of delivery for selected drugs to the cochlea are missing. Herein, in this study NGF was administered by the intranasal route. The first part of the study was focused on a biodistribution study, which showed the effective delivery in the cochlea; while the second part was focused on analyzing the potential therapeutic effect of NGF in senescence-accelerated prone strain 8 mice. Interestingly, intranasal administration of NGF resulted protective in counteracting hearing impairment in SAMP8 mice, ameliorating hearing performances (analyzed by auditory brainstem responses and distortion product otoacoustic emission) and hair cells morphology (analyzed by microscopy analysis). The results obtained were encouraging indicating that the neurotrophin NGF was efficiently delivered to the inner ear and that it was effective in counteracting hearing loss.

PMID:37704645 | DOI:10.1038/s41419-023-06100-8

SOURCE:
Cell death & disease

PUBLISHER:

PMID:
pubmed:37704645

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:37704645

DOI:
10.1038/s41419-023-06100-8

DATE – PUBLISHED:
Wed, 13 Sep 2023 06:00:00 -0400

DATE – DOI:
2023-09-13T13:02:14Z

DATE – ADDED:
09/14/23 12:38AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37704645/

LINK – DOI:
https://doi.org/10.1038/s41419-023-06100-8

LINK – PUBLISHER:
https://www.nature.com/articles/s41419-023-06100-8?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-09-14T04:38:29+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Loss of synaptic ribbons is an early cause in ROS-induced acquired sensorineural hearing loss

CONTENT:
Neurobiol Dis. 2023 Sep 2:106280. doi: 10.1016/j.nbd.2023.106280. Online ahead of print.

ABSTRACT

Considerable evidence of reactive oxygen species (ROS) involvement in cochlear hair cell (HC) loss, leading to acquired sensorineural hearing loss (SNHL), were reported. Cochlear synaptopathy between HCs and spiral ganglion neurons has been gathering attention as a cochlear HC loss precursor not detectable by normal auditory evaluation. However, the molecular mechanisms linking ROS with HC loss, as well as the relationship between ROS and cochlear synaptopathy have not been elucidated. Here, we examined these linkages using NOX4-TG mice, which constitutively produce ROS without stimulation. mRNA levels of Piccolo 1, a major component of the synaptic ribbon (a specialized structure surrounded by synaptic vesicles in HCs), were decreased in postnatal day 6 NOX4-TG mice cochleae compared to those in WT mice; they were also decreased by noise exposure in 2-week-old WT cochleae. As noise exposure induces ROS production, this suggests that the synaptic ribbon is a target of ROS. The level of CtBP2, another synaptic ribbon component, was significantly lower in NOX4-TG cochleae of 1-month-old and 4-month-old mice compared to that in WT mice, although no significant differences were noted at 1.5- and 2-months. The decrease in CtBP2 plateaued in 4-month-old NOX4-TG, while it gradually decreased from 1 to 6 months in WT mice. Furthermore, CtBP2 level in 2-month-old NOX4-TG mice decreased significantly after exposure to cisplatin and noise compared to that in WT mice. These findings suggest that ROS lead to developmental delays and early degeneration of synaptic ribbons, which could be potential targets for novel therapeutics for ROS-induced SNHL.

PMID:37666363 | DOI:10.1016/j.nbd.2023.106280

SOURCE:
Neurobiology of disease

PUBLISHER:

PMID:
pubmed:37666363

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:37666363

DOI:
10.1016/j.nbd.2023.106280

DATE – PUBLISHED:
Mon, 04 Sep 2023 06:00:00 -0400

DATE – DOI:
2023-09-04T05:00:39Z

DATE – ADDED:
09/05/23 12:38AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37666363/

LINK – DOI:
https://doi.org/10.1016/j.nbd.2023.106280

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S0969996123002954?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-09-05T04:38:17+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Key genes and potential drugs in age-related hearing loss: transcriptome analysis of cochlear hair cells in old mice

CONTENT:
Cell Mol Biol (Noisy-le-grand). 2023 Jun 30;69(6):67-74. doi: 10.14715/cmb/2023.69.6.11.

ABSTRACT

This study aimed to dig new molecular mechanisms and medications for age-related hearing loss (ARHL or presbycusis) by extracting common results of publicly available datasets. Based on five datasets (GSE153882, GSE121856, GSE98070, GSE45026, and GSE98071) in studies of cochlear hair cells, we explored the interrelationships among presbycusis-related genes, including gene interactions, enrichment analysis, miRNA-mRNA matching pairs, and potential new drugs. Together, there were 25 common increased mRNAs. A total of 183 drugs can simultaneously target 11 of these mRNAs. In the interaction network, hub genes included: Cbln1, Prl, Mpp6 and Gh. Meanwhile, there were 74 common decreased mRNAs. The hub genes include Cdkn1a, Egr1, and Ctgf. After de-duplication, the 25 common increased mRNAs had 946 matched miRNAs, with 34 decreased ones; and the 74 decreased mRNAs had 1164 matched miRNAs, with 26 increased ones. Between the inhibitors of increased mRNAs and enhancers of decreased mRNAs, there were 26 common drugs. Besides, we discovered six key genes that may play a crucial role in the onset of presbycusis. In conclusion, by jointly analyzing multiple datasets, we found 25 common increased mRNAs (e.g., Cbln1, Prl, Mpp6 and Gh) and 74 common decreased mRNAs (Cdkn1a, Egr1, and Ctgf), as well as 34 potential therapeutic miRNAs and 26 pathogenic miRNAs, and three candidate drugs (calcitriol, diclofenac, and diethylstilbestrol). They may provide new targets and strategies for mechanistic and therapeutic studies in ARHL.

PMID:37605587 | DOI:10.14715/cmb/2023.69.6.11

SOURCE:
Cellular and molecular biology (Noisy-le-Grand, France)

PUBLISHER:

PMID:
pubmed:37605587

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:37605587

DOI:
10.14715/cmb/2023.69.6.11

DATE – PUBLISHED:
Tue, 22 Aug 2023 06:00:00 -0400

DATE – DOI:
2023-08-17T17:40:54Z

DATE – ADDED:
08/22/23 06:39AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37605587/

LINK – DOI:
https://doi.org/10.14715/cmb/2023.69.6.11

LINK – PUBLISHER:
https://cellmolbiol.org/index.php/CMB/article/view/4807?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-08-22T10:39:03+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Reversal of an existing hearing loss by gene activation in Spns2 mutant mice

CONTENT:
Proc Natl Acad Sci U S A. 2023 Aug 22;120(34):e2307355120. doi: 10.1073/pnas.2307355120. Epub 2023 Aug 8.

ABSTRACT

Hearing loss is highly heterogeneous, but one common form involves a failure to maintain the local ionic environment of the sensory hair cells reflected in a reduced endocochlear potential. We used a genetic approach to ask whether this type of pathology can be reversed, using the Spns2tm1a mouse mutant known to show this defect. By activating Spns2 gene transcription at different ages after the onset of hearing loss, we found that an existing auditory impairment can be reversed to give close to normal thresholds for an auditory brainstem response (ABR), at least at low to mid stimulus frequencies. Delaying the activation of Spns2 led to less effective recovery of ABR thresholds, suggesting that there is a critical period for intervention. Early activation of Spns2 not only led to improvement in auditory function but also to protection of sensory hair cells from secondary degeneration. The genetic approach we have used to establish that this type of hearing loss is in principle reversible could be extended to many other diseases using available mouse resources.

PMID:37552762 | DOI:10.1073/pnas.2307355120

SOURCE:
Proceedings of the National Academy of Sciences of the United States of America

PUBLISHER:

PMID:
pubmed:37552762

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:37552762

DOI:
10.1073/pnas.2307355120

DATE – PUBLISHED:
Tue, 08 Aug 2023 06:00:00 -0400

DATE – DOI:
2023-08-08T17:47:01Z

DATE – ADDED:
08/08/23 06:37PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37552762/

LINK – DOI:
https://doi.org/10.1073/pnas.2307355120

LINK – PUBLISHER:
https://pnas.org/doi/10.1073/pnas.2307355120?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-08-08T22:37:48+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Pharmaceutical characterization of probucol bile acid-lithocholic acid nanoparticles to prevent chronic hearing related and similar cellular oxidative stress pathologies

CONTENT:
Nanomedicine (Lond). 2023 May;18(12):923-940. doi: 10.2217/nnm-2023-0092. Epub 2023 Aug 2.

ABSTRACT

Background: Sensorineural hearing loss has been associated with oxidative stress. However, an antioxidant that passes effectively through the ear remains elusive. Method: Probucol (PB)-based nanoparticles were formed using a spray-drying encapsulation technique, characterized and tested in vitro . Results: Uniform, spherical nanoparticles were produced. The addition of lithocholic acid to PB formulations did not affect drug content or production yield, but it did modify capsule size, surface tension, electrokinetic stability and drug release. Cell viability, bioenergetics and inflammatory profiles were improved when auditory cells were exposed to PB-based nanoparticles, which showed antioxidant properties (p < 0.05). Conclusion: PB-based nanoparticles can potentially protect the auditory cell line from oxidative stress and could be used in future in vivo studies as a potential new therapeutic agent for sensorineural hearing loss. PMID:37529927 | DOI:10.2217/nnm-2023-0092 SOURCE: Nanomedicine (London, England) PUBLISHER: PMID: pubmed:37529927 ID: 0b58ea4968e09ff10f4e1238c494f316pubmed:37529927 DOI: 10.2217/nnm-2023-0092 DATE - PUBLISHED: Wed, 02 Aug 2023 06:00:00 -0400 DATE - DOI: 2023-08-02T09:25:45Z DATE - ADDED: 08/09/23 06:40AM LINK - PUBMED: https://pubmed.ncbi.nlm.nih.gov/37529927/ LINK - DOI: https://doi.org/10.2217/nnm-2023-0092 LINK - PUBLISHER: https://www.futuremedicine.com/doi/10.2217/nnm-2023-0092?utm_source=hearinglosstreatmentreport.com IMAGE: REFERENCE: Hearing Loss Treatment Report, Urgent Research, 2023-08-09T10:40:46+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Space Station-like Composite Nanoparticles for Co-Delivery of Multiple Natural Compounds from Chinese Medicine and Hydrogen in Combating Sensorineural Hearing Loss

CONTENT:
Mol Pharm. 2023 Jul 28. doi: 10.1021/acs.molpharmaceut.3c00177. Online ahead of print.

ABSTRACT

Ototoxic drugs such as aminoglycoside antibiotics and cisplatin (CDDP) can cause sensorineural hearing loss (SNHL), which is closely related to oxidative stress and the acidification of the inner ear microenvironment. Effective treatment of SNHL often requires multifaceted approach due to the complex pathology, and drug combination therapy is expected to be at the forefront of modern hearing loss treatment. Here, space-station-like composite nanoparticles (CCC@mPP NPs) with pH/oxidation dual responsiveness and multidrug simultaneous delivery capability were constructed and then loaded with various drugs including panax notoginseng saponins (PNS), tanshinone IIA (TSIIA), and ammonia borane (AB) to provide robust protection against SNHL. Molecular dynamics simulation revealed that carboxymethyl chitosan/calcium carbonate-chitosan (CCC) NPs and monomethoxy poly(ethylene glycol)-PLGA (mPP) NPs can rendezvous and dock primarily by hydrogen bonding, and electrostatic forces may be involved. Moreover, CCC@mPP NPs crossed the round window membrane (RWM) and entered the inner ear through endocytosis and paracellular pathway. The docking state was basically maintained during this process, which created favorable conditions for multidrug delivery. This nanosystem was highly sensitive to pH and reactive oxygen species (ROS) changes, as evidenced by the restricted release of payload at alkaline condition (pH 7.4) without ROS, while significantly promoting the release in acidic condition (pH 5.0 and 6.0) with ROS. TSIIA/PNS/AB-loaded CCC@mPP NPs almost completely preserved the hair cells and remained the hearing threshold shift within normal limits in aminoglycoside- or CDDP-treated guinea pigs. Further experiments demonstrated that the protective mechanisms of TSIIA/PNS/AB-loaded CCC@mPP NPs involved direct and indirect scavenging of excessive ROS, and reduced release of pro-inflammatory cytokines. Both in vitro and in vivo experiments showed the high biocompatibility of the composite NPs, even after long-term administration. Collectively, this work suggests that composite NPs is an ideal multi-drug-delivery vehicle and open new avenues for inner ear disease therapies.

PMID:37503854 | DOI:10.1021/acs.molpharmaceut.3c00177

SOURCE:
Molecular pharmaceutics

PUBLISHER:

PMID:
pubmed:37503854

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:37503854

DOI:
10.1021/acs.molpharmaceut.3c00177

DATE – PUBLISHED:
Fri, 28 Jul 2023 06:00:00 -0400

DATE – DOI:
2023-07-28T11:09:19Z

DATE – ADDED:
07/28/23 01:07PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37503854/

LINK – DOI:
https://doi.org/10.1021/acs.molpharmaceut.3c00177

LINK – PUBLISHER:
https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.3c00177?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-07-28T17:07:27+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Altered Fhod3 Expression Involved in Progressive High-Frequency Hearing Loss via Dysregulation of Actin Polymerization Stoichiometry in The Cuticular Plate

CONTENT:
bioRxiv. 2023 Jul 25:2023.07.20.549974. doi: 10.1101/2023.07.20.549974. Preprint.

ABSTRACT

Age-related hearing loss (ARHL) is a common sensory impairment with comlex underlying mechanisms. In our previous study, we performed a meta-analysis of genome-wide association studies (GWAS) in mice and identified a novel locus on chromosome 18 associated with ARHL specifically linked to a 32 kHz tone burst stimulus. Consequently, we investigated the role of Formin Homology 2 Domain Containing 3 (Fhod3), a newly discovered candidate gene for ARHL based on the GWAS results. We observed Fhod3 expression in auditory hair cells (HCs) and primarily localized at the cuticular plate (CP). To understand the functional implications of Fhod3 in the cochlea, we generated Fhod3 overexpression mice ( Pax2-Cre +/- ; Fhod3 Tg/+ ) (TG) and HC-specific conditional knockout mice ( Atoh1-Cre +/- ; Fhod3 fl/fl ) (KO). Audiological assessments in TG mice demonstrated progressive high-frequency hearing loss, characterized by predominant loss of outer HCs and decrease phalloidin intensities of CP. Ultrastructural analysis revealed shortened stereocilia in the basal turn cochlea. Importantly, the hearing and HC phenotype in TG mice were replicated in KO mice. These findings indicate that Fhod3 plays a critical role in regulating actin dynamics in CP and stereocilia. Further investigation of Fhod3-related hearing impairment mechanisms may facilitate the development of therapeutic strategies for ARHL in humans.

PMID:37546952 | PMC:PMC10401921 | DOI:10.1101/2023.07.20.549974

SOURCE:
bioRxiv : the preprint server for biology

PUBLISHER:

PMID:
pubmed:37546952

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:37546952

DOI:
10.1101/2023.07.20.549974

DATE – PUBLISHED:
Mon, 07 Aug 2023 06:00:00 -0400

DATE – DOI:
2023-07-25T13:10:17Z

DATE – ADDED:
08/07/23 06:38AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37546952/

LINK – DOI:
https://doi.org/10.1101/2023.07.20.549974

LINK – PUBLISHER:
http://biorxiv.org/lookup/doi/10.1101/2023.07.20.549974?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-08-07T10:38:17+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Long-term NAD+ supplementation prevents the progression of age-related hearing loss in mice

CONTENT:
Aging Cell. 2023 Jul 3. doi: 10.1111/acel.13909. Online ahead of print.

ABSTRACT

Age-related hearing loss (ARHL) is the most common sensory disability associated with human aging. Yet, there are no approved measures for preventing or treating this debilitating condition. With its slow progression, continuous and safe approaches are critical for ARHL treatment. Nicotinamide Riboside (NR), a NAD+ precursor, is well tolerated even for long-term use and is already shown effective in various disease models including Alzheimer’s and Parkinson’s disease. It has also been beneficial against noise-induced hearing loss and in hearing loss associated with premature aging. However, its beneficial impact on ARHL is not known. Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL. Through transcriptomic and biochemical analysis, we find that NR administration restores age-associated reduction in cochlear NAD+ levels, upregulates biological pathways associated with synaptic transmission and PPAR signaling, and reduces the number of orphan ribbon synapses between afferent auditory neurons and inner hair cells. We also find that NR targets a novel pathway of lipid droplets in the cochlea by inducing the expression of CIDEC and PLIN1 proteins that are downstream of PPAR signaling and are key for lipid droplet growth. Taken together, our results demonstrate the therapeutic potential of NR treatment for ARHL and provide novel insights into its mechanism of action.

PMID:37395319 | DOI:10.1111/acel.13909

SOURCE:
Aging cell

PUBLISHER:

PMID:
pubmed:37395319

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:37395319

DOI:
10.1111/acel.13909

DATE – PUBLISHED:
Mon, 03 Jul 2023 06:00:00 -0400

DATE – DOI:
2023-07-03T10:36:58Z

DATE – ADDED:
07/03/23 01:02PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37395319/

LINK – DOI:
https://doi.org/10.1111/acel.13909

LINK – PUBLISHER:
https://onlinelibrary.wiley.com/doi/10.1111/acel.13909?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-07-03T17:02:15+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
A prestin-targeting peptide-guided drug delivery system rearranging concentration gradient in the inner ear: an improved strategy against hearing loss

CONTENT:
Eur J Pharm Sci. 2023 Jun 7:106490. doi: 10.1016/j.ejps.2023.106490. Online ahead of print.

ABSTRACT

Hearing loss is mainly due to outer hair cell (OHC) damage in three cochlear turns. Local administration via the round window membrane (RWM) has considerable otological clinical potential in bypassing the blood-labyrinth barrier. However, insufficient drug distribution in the apical and middle cochlear turns results in unsatisfactory efficacy. We functionalized poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) with targeting peptide A665, which specifically bound to prestin, a protein uniquely expressed in OHCs. The modification facilitated the cellular uptake and RWM permeability of NPs. Notably, the guide of A665 towards OHCs enabled more NPs perfusion in the apical and middle cochlear turns without decreasing accumulation in the basal cochlear turn. Subsequently, curcumin (CUR), an appealing anti-ototoxic drug, was encapsulated in NPs. In aminoglycoside-treated guinea pigs with the worst hearing level, CUR/A665-PLGA NPs, with superior performance to CUR/PLGA NPs, almost completely preserved the OHCs in three cochlear turns. The lack of increased low-frequencies hearing thresholds further confirmed that the delivery system with prestin affinity mediated cochlear distribution rearrangement. Good inner ear biocompatibility and little or no embryonic zebrafish toxicity were observed throughout the treatment. Overall, A665-PLGA NPs act as desirable tools with sufficient inner ear delivery for improved efficacy against severe hearing loss.

PMID:37295658 | DOI:10.1016/j.ejps.2023.106490

SOURCE:
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences

PUBLISHER:

PMID:
pubmed:37295658

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:37295658

DOI:
10.1016/j.ejps.2023.106490

DATE – PUBLISHED:
Fri, 09 Jun 2023 06:00:00 -0400

DATE – DOI:
2023-06-07T19:39:18Z

DATE – ADDED:
06/10/23 03:11PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37295658/

LINK – DOI:
https://doi.org/10.1016/j.ejps.2023.106490

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S0928098723001203?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-06-10T19:11:26+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Mitochondrial alterations in the cochlea of Cdk5rap1-knockout mice with age-related hearing loss

CONTENT:
FEBS Open Bio. 2023 May 31. doi: 10.1002/2211-5463.13655. Online ahead of print.

ABSTRACT

Previous studies have revealed that age-related hearing loss (AHL) in Cdk5 regulatory subunit associated protein 1 (Cdk5rap1)-knockout mice is associated with pathology in the cochlea. Here, we aimed to identify mitochondrial alterations in the cochlea of Cdk5rap1-knockout mice with AHL. Mitochondria in the spiral ganglion neurons (SGNs) and hair cells (HCs) were normal despite senescence; however, the mitochondria of types I, II, and IV spiral ligament fibrocytes were ballooned, damaged, and ballooned, respectively, in the stria vascularis. Our results suggest that the accumulation of dysfunctional mitochondria in the lateral wall, rather than the loss of HCs and SGNs, leads to the onset of AHL. Our results provide valuable information regarding the underlying mechanisms of AHL and the relationship between aberrant transfer RNA modification-induced hearing loss and mitochondrial dysfunction.

PMID:37258461 | DOI:10.1002/2211-5463.13655

SOURCE:
FEBS open bio

PUBLISHER:

PMID:
pubmed:37258461

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:37258461

DOI:
10.1002/2211-5463.13655

DATE – PUBLISHED:
Wed, 31 May 2023 06:00:00 -0400

DATE – DOI:
2023-06-01T02:25:44Z

DATE – ADDED:
06/01/23 01:04AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37258461/

LINK – DOI:
https://doi.org/10.1002/2211-5463.13655

LINK – PUBLISHER:
https://febs.onlinelibrary.wiley.com/doi/10.1002/2211-5463.13655?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-06-01T05:04:23+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Chromodomain helicase DNA binding protein 4 in cell fate decisions

CONTENT:
Hear Res. 2023 Sep 1;436:108813. doi: 10.1016/j.heares.2023.108813. Epub 2023 May 30.

ABSTRACT

Loss of spiral ganglion neurons (SGNs) in the cochlea causes hearing loss. Understanding the mechanisms of cell fate transition accelerates efforts that employ directed differentiation and lineage conversion to repopulate lost SGNs. Proposed strategies to regenerate SGNs rely on altering cell fate by activating transcriptional regulatory networks, but repressing networks for alternative cell lineages is also essential. Epigenomic changes during cell fate transitions suggest that CHD4 represses gene expression by altering the chromatin status. Despite limited direct investigations, human genetic studies implicate CHD4 function in the inner ear. The possibility of CHD4 in suppressing alternative cell fates to promote inner ear regeneration is discussed.

PMID:37329862 | DOI:10.1016/j.heares.2023.108813

SOURCE:
Hearing research

PUBLISHER:

PMID:
pubmed:37329862

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:37329862

DOI:
10.1016/j.heares.2023.108813

DATE – PUBLISHED:
Sat, 17 Jun 2023 06:00:00 -0400

DATE – DOI:
2023-05-31T04:34:19Z

DATE – ADDED:
07/12/23 06:38AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37329862/

LINK – DOI:
https://doi.org/10.1016/j.heares.2023.108813

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S0378595523001259?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-07-12T10:38:27+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Development and evaluation of helper dependent adenoviral vectors for inner ear gene delivery

CONTENT:
Hear Res. 2023 Aug;435:108819. doi: 10.1016/j.heares.2023.108819. Epub 2023 May 26.

ABSTRACT

Viral vector gene therapy is an attractive strategy to treat hearing loss. Since hearing loss is due to a variety of pathogenic signaling cascades in distinct cells, viral vectors that can express large or multiple genes in a cell-type specific manner are needed. Helper-dependent adenoviral vectors (HdAd) are safe viral vectors with a large packaging capacity (-36 kb). Despite the potential of HdAd, its use in the inner ear is largely unexplored. Therefore, to evaluate the utility of HdAd for inner ear gene therapy, we created two HdAd vectors that use distinct cellular receptors for transduction: HdAd Serotype Type 5 (HdAd5), the Coxsackie-Adenovirus Receptor (CAR) and a chimeric HdAd 5/35, the human CD46+ receptor (hCD46). We delivered these vectors through the round window (RW) or scala media in CBA/J, C57Bl6/J and hCD46 transgenic mice. Immunostaining in conjunction with confocal microscopy of cochlear sections revealed that multiple cell types were transduced using HdAd5 and HdAd 5/35 in all mouse models. Delivery of HdAd5 via RW in the C57Bl/6 J or CBA/J cochlea resulted in transduced mesenchymal cells of the peri‑lymphatic lining and modiolar region while scala media delivery resulted in transduction of supporting cells and inner hair cells. Hd5/35 transduction was CD46 dependent and RW delivery of HdAd5/35 in the hCD46 mouse model resulted in a similar transduction pattern as HdAd5 in the peri‑lymphatic lining and modiolar region in the cochlea. Our data indicate that HdAd vectors are promising vectors for use in inner ear gene therapy to treat some causes of hearing loss.

PMID:37276687 | DOI:10.1016/j.heares.2023.108819

SOURCE:
Hearing research

PUBLISHER:

PMID:
pubmed:37276687

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:37276687

DOI:
10.1016/j.heares.2023.108819

DATE – PUBLISHED:
Mon, 05 Jun 2023 06:00:00 -0400

DATE – DOI:
2023-05-26T06:25:37Z

DATE – ADDED:
06/19/23 01:05PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37276687/

LINK – DOI:
https://doi.org/10.1016/j.heares.2023.108819

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S0378595523001314?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-06-19T17:05:20+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
The applications of Targeted Delivery for Gene Therapies in Hearing Loss

CONTENT:
J Drug Target. 2023 May 21:1-22. doi: 10.1080/1061186X.2023.2216900. Online ahead of print.

ABSTRACT

Gene therapies are becoming more abundantly researched for use in a multitude of potential treatments, including for hearing loss. Hearing loss is a condition which impacts an increasing number of the population each year, with significant burdens associated. As such, this review will present the concept that delivering a gene effectively to the inner ear may assist in expanding novel treatment options and improving patient outcomes. Historically, several drawbacks have been associated with the use of gene therapies, some of which may be overcome via targeted delivery. Targeted delivery has the potential to alleviate off-target effects and permit a safer delivery profile. Viral vectors have often been described as a delivery method, however, there is an emerging depiction of the potential for nanotechnology to be used. Resulting nanoparticles may also be tuned to allow for targeted delivery. Therefore, this review will focus on hearing loss, gene delivery techniques and inner ear targets, including highlighting promising research. Targeted delivery is a key concept to permitting gene delivery in a safe effective manner, however, further research is required, both in the determination of genes to use in functional hearing recovery and formulating nanoparticles for targeted delivery.

PMID:37211674 | DOI:10.1080/1061186X.2023.2216900

SOURCE:
Journal of drug targeting

PUBLISHER:

PMID:
pubmed:37211674

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:37211674

DOI:
10.1080/1061186X.2023.2216900

DATE – PUBLISHED:
Mon, 22 May 2023 06:00:00 -0400

DATE – DOI:
2023-05-22T04:39:23Z

DATE – ADDED:
05/22/23 06:38AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37211674/

LINK – DOI:
https://doi.org/10.1080/1061186X.2023.2216900

LINK – PUBLISHER:
https://www.tandfonline.com/doi/full/10.1080/1061186X.2023.2216900?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-05-22T10:38:48+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
The applications of CRISPR/Cas-mediated genome editing in genetic hearing loss

CONTENT:
Cell Biosci. 2023 May 20;13(1):93. doi: 10.1186/s13578-023-01021-7.

ABSTRACT

Hearing loss (HL) can be caused by a number of different genetic factors. Non-syndromic HL refers that HL occurs as an isolated symptom in an individual, whereas syndromic HL refers that HL is associated with other symptoms or abnormalities. To date, more than 140 genes have been identified as being associated with non-syndromic HL, and approximately 400 genetic syndromes can include HL as one of the clinical symptoms. However, no gene therapeutic approaches are currently available to restore or improve hearing. Therefore, there is an urgent necessity to elucidate the possible pathogenesis of specific mutations in HL-associated genes and to investigate the promising therapeutic strategies for genetic HL. The development of the CRISPR/Cas system has revolutionized the field of genome engineering, which has become an efficacious and cost-effective tool to foster genetic HL research. Moreover, several in vivo studies have demonstrated the therapeutic efficacy of the CRISPR/Cas-mediated treatments for specific genetic HL. In this review, we briefly introduce the progress in CRISPR/Cas technique as well as the understanding of genetic HL, and then we detail the recent achievements of CRISPR/Cas technique in disease modeling and therapeutic strategies for genetic HL. Furthermore, we discuss the challenges for the application of CRISPR/Cas technique in future clinical treatments.

PMID:37210555 | DOI:10.1186/s13578-023-01021-7

SOURCE:
Cell & bioscience

PUBLISHER:

PMID:
pubmed:37210555

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:37210555

DOI:
10.1186/s13578-023-01021-7

DATE – PUBLISHED:
Sat, 20 May 2023 06:00:00 -0400

DATE – DOI:
2023-05-20T07:01:33Z

DATE – ADDED:
05/21/23 01:01AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37210555/

LINK – DOI:
https://doi.org/10.1186/s13578-023-01021-7

LINK – PUBLISHER:
https://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-023-01021-7?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-05-21T05:01:16+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Peroxisome Deficiency in Cochlear Hair Cells Causes Hearing Loss by Deregulating BK Channels

CONTENT:
Adv Sci (Weinh). 2023 May 12:e2300402. doi: 10.1002/advs.202300402. Online ahead of print.

ABSTRACT

The peroxisome is a ubiquitous organelle in rodent cells and plays important roles in a variety of cell types and tissues. It is previously indicated that peroxisomes are associated with auditory function, and patients with peroxisome biogenesis disorders (PBDs) are found to have hearing dysfunction, but the specific role of peroxisomes in hearing remains unclear. In this study, two peroxisome-deficient mouse models (Atoh1-Pex5-/- and Pax2-Pex5-/- ) are established and it is found that peroxisomes mainly function in the hair cells of cochleae. Furthermore, peroxisome deficiency-mediated negative effects on hearing do not involve mitochondrial dysfunction and oxidative damage. Although the mammalian target of rapamycin complex 1 (mTORC1) signaling is shown to function through peroxisomes, no changes are observed in the mTORC1 signaling in Atoh1-Pex5-/- mice when compared to wild-type (WT) mice. However, the expression of large-conductance, voltage-, and Ca2+ -activated K+ (BK) channels is less in Atoh1-Pex5-/- mice as compared to the WT mice, and the administration of activators of BK channels (NS-1619 and NS-11021) restores the auditory function in knockout mice. These results suggest that peroxisomes play an essential role in cochlear hair cells by regulating BK channels. Hence, BK channels appear as the probable target for treating peroxisome-related hearing diseases such as PBDs.

PMID:37171794 | DOI:10.1002/advs.202300402

SOURCE:
Advanced science (Weinheim, Baden-Wurttemberg, Germany)

PUBLISHER:

PMID:
pubmed:37171794

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:37171794

DOI:
10.1002/advs.202300402

DATE – PUBLISHED:
Fri, 12 May 2023 06:00:00 -0400

DATE – DOI:
2023-05-12T15:33:07Z

DATE – ADDED:
05/12/23 01:04PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37171794/

LINK – DOI:
https://doi.org/10.1002/advs.202300402

LINK – PUBLISHER:
https://onlinelibrary.wiley.com/doi/10.1002/advs.202300402?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-05-12T17:04:48+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Piceatannol protects against age-related hearing loss by inhibiting cellular pyroptosis and inflammation through regulated Caspase11-GSDMD pathway

CONTENT:
Biomed Pharmacother. 2023 Apr 24;163:114704. doi: 10.1016/j.biopha.2023.114704. Online ahead of print.

ABSTRACT

Age-related hearing loss (ARHL) is a common issue associated with aging. One of the typical causes of hearing loss is the damage to inner ear hair cells. In addition, oxidative stress and inflammation contribute to ARHL. To avoid excessive inflammatory responses, non-classical scorch death pathway by cell membrane lipopolysaccharide (LPS) activates of caspase-11. Piceatannol (PCT) is also known for anti-tumor, antioxidant and anti-inflammatory effects; however, the protective effect of piceatannol (PCT) on ARHL is unclear. The aim of this study was to elucidate the mechanism underlying protective effect of PCT on ARHL-induced inner ear hair cell damage. In vivo experiments showed that PCT could protect mice from inflammatory aging-induced hearing loss as well as from inner hair cells (IHC) and spiral ganglion (SG) deficits. In addition, inflammatory vesicle inhibitor BAY11-7082 ameliorated ARHL, inhibited NLRP3 and reduced GSDMD expression. In in vitro experiments we used LPS and D-gal to simulate the aging inflammatory environment. The results showed that intracellular reactive oxygen species levels, expression of Caspase-11, NLRP3, and GSDMD were significantly increased, yet treatment with PCT or BAY11-7082 significantly improved HEI-OC-1 cell injury while reducing inflammation-associated protein expression as well as the occurrence of pyroptosis. In conclusion, these results suggest a protective role for PCT against ARHL, possibly through Caspase-11-GSDMD pathway. Our findings may provide a new target and theoretical basis for hearing loss treatment using PCT.

PMID:37100013 | DOI:10.1016/j.biopha.2023.114704

SOURCE:
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

PUBLISHER:

PMID:
pubmed:37100013

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:37100013

DOI:
10.1016/j.biopha.2023.114704

DATE – PUBLISHED:
Wed, 26 Apr 2023 06:00:00 -0400

DATE – DOI:
2023-04-24T09:01:12Z

DATE – ADDED:
04/27/23 12:38AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37100013/

LINK – DOI:
https://doi.org/10.1016/j.biopha.2023.114704

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S0753332223004924?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-04-27T04:38:01+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Antioxidant Therapy as an Effective Strategy against Noise-Induced Hearing Loss: From Experimental Models to Clinic

CONTENT:
Life (Basel). 2023 Apr 17;13(4):1035. doi: 10.3390/life13041035.

ABSTRACT

Cochlear redox unbalance is the main mechanism of damage involved in the pathogenesis of noise-induced-hearing loss. Indeed, the increased free radical production, in conjunction with a reduced efficacy of the endogenous antioxidant system, plays a key role in cochlear damage induced by noise exposure. For this reason, several studies focused on the possibility to use exogenous antioxidant to prevent or attenuate noise-induce injury. Thus, several antioxidant molecules, alone or in combination with other compounds, have been tested in both experimental and clinical settings. In our findings, we tested the protective effects of several antioxidant enzymes, spanning from organic compounds to natural compounds, such as nutraceuticals of polyphenols. In this review, we summarize and discuss the strengths and weaknesses of antioxidant supplementation focusing on polyphenols, Q-Ter, the soluble form of CoQ10, Vitamin E and N-acetil-cysteine, which showed great otoprotective effects in different animal models of noise induced hearing loss and which has been proposed in clinical trials.

PMID:37109564 | DOI:10.3390/life13041035

SOURCE:
Life (Basel, Switzerland)

PUBLISHER:

PMID:
pubmed:37109564

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:37109564

DOI:
10.3390/life13041035

DATE – PUBLISHED:
Fri, 28 Apr 2023 06:00:00 -0400

DATE – DOI:
2023-04-18T06:59:06Z

DATE – ADDED:
04/28/23 06:39AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37109564/

LINK – DOI:
https://doi.org/10.3390/life13041035

LINK – PUBLISHER:
https://www.mdpi.com/2075-1729/13/4/1035?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-04-28T10:39:16+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Reprogramming by drug-like molecules leads to regeneration of cochlear hair cell-like cells in adult mice

CONTENT:
Proc Natl Acad Sci U S A. 2023 Apr 25;120(17):e2215253120. doi: 10.1073/pnas.2215253120. Epub 2023 Apr 17.

ABSTRACT

Strategies to overcome irreversible cochlear hair cell (HC) damage and loss in mammals are of vital importance to hearing recovery in patients with permanent hearing loss. In mature mammalian cochlea, co-activation of Myc and Notch1 reprograms supporting cells (SC) and promotes HC regeneration. Understanding of the underlying mechanisms may aid the development of a clinically relevant approach to achieve HC regeneration in the nontransgenic mature cochlea. By single-cell RNAseq, we show that MYC/NICD “rejuvenates” the adult mouse cochlea by activating multiple pathways including Wnt and cyclase activator of cyclic AMP (cAMP), whose blockade suppresses HC-like cell regeneration despite Myc /Notch activation. We screened and identified a combination (the cocktail) of drug-like molecules composing of small molecules and small interfering RNAs to activate the pathways of Myc, Notch1, Wnt and cAMP. We show that the cocktail effectively replaces Myc and Notch1 transgenes and reprograms fully mature wild-type (WT) SCs for HC-like cells regeneration in vitro. Finally, we demonstrate the cocktail is capable of reprogramming adult cochlea for HC-like cells regeneration in WT mice with HC loss in vivo. Our study identifies a strategy by a clinically relevant approach to reprogram mature inner ear for HC-like cells regeneration, laying the foundation for hearing restoration by HC regeneration.

PMID:37068229 | DOI:10.1073/pnas.2215253120

SOURCE:
Proceedings of the National Academy of Sciences of the United States of America

PUBLISHER:

PMID:
pubmed:37068229

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:37068229

DOI:
10.1073/pnas.2215253120

DATE – PUBLISHED:
Mon, 17 Apr 2023 06:00:00 -0400

DATE – DOI:
2023-04-17T19:12:29Z

DATE – ADDED:
04/17/23 06:38PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37068229/

LINK – DOI:
https://doi.org/10.1073/pnas.2215253120

LINK – PUBLISHER:
https://pnas.org/doi/10.1073/pnas.2215253120?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-04-17T22:38:19+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Enhanced survival of hypoimmunogenic otic progenitors following intracochlear xenotransplantation: repercussions for stem cell therapy in hearing loss models

CONTENT:
Stem Cell Res Ther. 2023 Apr 12;14(1):83. doi: 10.1186/s13287-023-03304-9.

ABSTRACT

Stem cell replacement holds the potential for sensorineural hearing loss (SNHL) treatment. However, its translation into clinical practice requires strategies for improving stem cell survival following intracochlear transplantation. Considering recent findings showing that the inner ear contains a resident population of immune cells, we hypothesized that immune evasion would improve the survival and residence time of transplanted stem cells in the cochlea, potentially leading to better outcomes. To test this, we leveraged genetic engineering techniques to develop hypoimmunogenic human-induced pluripotent stem cells (hi-iPSC), which lack human leukocyte antigen expression. We found that gene editing does not affect the biological properties of hi-iPSCs, including their capacity to differentiate into otic neural progenitors (ONPs). Compared to wild-type ONPs, more hypoimmunogenic ONPs (derived from hi-iPSCs) were found in the inner ear of immunocompetent mice ten days following cochlear xenotransplantation. This approach may open a new avenue for experimental and clinical SNHL treatments.

PMID:37046329 | DOI:10.1186/s13287-023-03304-9

SOURCE:
Stem cell research & therapy

PUBLISHER:

PMID:
pubmed:37046329

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:37046329

DOI:
10.1186/s13287-023-03304-9

DATE – PUBLISHED:
Wed, 12 Apr 2023 06:00:00 -0400

DATE – DOI:
2023-04-12T12:10:57Z

DATE – ADDED:
04/13/23 12:37AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37046329/

LINK – DOI:
https://doi.org/10.1186/s13287-023-03304-9

LINK – PUBLISHER:
https://stemcellres.biomedcentral.com/articles/10.1186/s13287-023-03304-9?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-04-13T04:37:46+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Amelioration of Sensorineural Hearing Loss through Regulation of Trpv1 , Cacna1h , and Ngf Gene Expression by a Combination of Cuscutae Semen and Rehmanniae Radix Preparata

CONTENT:
Nutrients. 2023 Apr 5;15(7):1773. doi: 10.3390/nu15071773.

ABSTRACT

Sensorineural hearing loss (SNHL) is a common condition that results from the loss of function of hair cells, which are responsible for converting sound into electrical signals within the cochlea and auditory nerve. Despite the prevalence of SNHL, a universally effective treatment has yet to be approved. To address this absence, the present study aimed to investigate the potential therapeutic effects of TS, a combination of Cuscutae Semen and Rehmanniae Radix Preparata. To this end, both in vitro and in vivo experiments were performed to evaluate the efficacy of TS with respect to SNHL. The results showed that TS was able to protect against ototoxic neomycin-induced damage in both HEI-OC1 cells and otic hair cells in zebrafish. Furthermore, in images obtained using scanning electron microscopy (SEM), an increase in the number of kinocilia, which was prompted by the TS treatment, was observed in the zebrafish larvae. In a noise-induced hearing loss (NIHL) mouse model, TS improved hearing thresholds as determined by the auditory brainstem response (ABR) test. Additionally, TS was found to regulate several genes related to hearing loss, including Trpv1 , Cacna1h , and Ngf , as determined by quantitative real-time polymerase chain reaction (RT-PCR) analysis. In conclusion, the findings of this study suggest that TS holds promise as a potential treatment for sensorineural hearing loss. Further research is necessary to confirm these results and evaluate the safety and efficacy of TS in a clinical setting.

PMID:37049613 | DOI:10.3390/nu15071773

SOURCE:
Nutrients

PUBLISHER:

PMID:
pubmed:37049613

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:37049613

DOI:
10.3390/nu15071773

DATE – PUBLISHED:
Thu, 13 Apr 2023 06:00:00 -0400

DATE – DOI:
2023-04-05T07:13:56Z

DATE – ADDED:
04/13/23 06:39AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/37049613/

LINK – DOI:
https://doi.org/10.3390/nu15071773

LINK – PUBLISHER:
https://www.mdpi.com/2072-6643/15/7/1773?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-04-13T10:39:57+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Crossmodal plasticity in hearing loss

CONTENT:
Trends Neurosci. 2023 Mar 27:S0166-2236(23)00045-0. doi: 10.1016/j.tins.2023.02.004. Online ahead of print.

ABSTRACT

Crossmodal plasticity is a textbook example of the ability of the brain to reorganize based on use. We review evidence from the auditory system showing that such reorganization has significant limits, is dependent on pre-existing circuitry and top-down interactions, and that extensive reorganization is often absent. We argue that the evidence does not support the hypothesis that crossmodal reorganization is responsible for closing critical periods in deafness, and crossmodal plasticity instead represents a neuronal process that is dynamically adaptable. We evaluate the evidence for crossmodal changes in both developmental and adult-onset deafness, which start as early as mild-moderate hearing loss and show reversibility when hearing is restored. Finally, crossmodal plasticity does not appear to affect the neuronal preconditions for successful hearing restoration. Given its dynamic and versatile nature, we describe how this plasticity can be exploited for improving clinical outcomes after neurosensory restoration.

PMID:36990952 | DOI:10.1016/j.tins.2023.02.004

SOURCE:
Trends in neurosciences

PUBLISHER:

PMID:
pubmed:36990952

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:36990952

DOI:
10.1016/j.tins.2023.02.004

DATE – PUBLISHED:
Wed, 29 Mar 2023 06:00:00 -0400

DATE – DOI:
2023-03-27T12:08:12Z

DATE – ADDED:
03/30/23 01:00AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/36990952/

LINK – DOI:
https://doi.org/10.1016/j.tins.2023.02.004

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S0166223623000450?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-03-30T05:00:45+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Valproic Acid Inhibits Progressive Hereditary Hearing Loss in a KCNQ4 Variant Model through HDAC1 Suppression

CONTENT:
Int J Mol Sci. 2023 Mar 16;24(6):5695. doi: 10.3390/ijms24065695.

ABSTRACT

Genetic or congenital hearing loss still has no definitive cure. Among genes related to genetic hearing loss, the potassium voltage-gated channel subfamily Q member 4 (KCNQ4) is known to play an essential role in maintaining ion homeostasis and regulating hair cell membrane potential. Variants of the KCNQ4 show reductions in the potassium channel activity and were responsible for non-syndromic progressive hearing loss. KCNQ4 has been known to possess a diverse variant. Among those variants, the KCNQ4 p.W276S variant produced greater hair cell loss related to an absence of potassium recycling. Valproic acid (VPA) is an important and commonly used histone deacetylase (HDAC) inhibitor for class I (HDAC1, 2, 3, and 8) and class IIa (HDAC4, 5, 7, and 9). In the current study, systemic injections of VPA attenuated hearing loss and protected the cochlear hair cells from cell death in the KCNQ4 p.W276S mouse model. VPA activated its known downstream target, the survival motor neuron gene, and increased acetylation of histone H4 in the cochlea, demonstrating that VPA treatment directly affects the cochlea. In addition, treatment with VPA increased the KCNQ4 binding with HSP90β by inhibiting HDAC1 activation in HEI-OC1 in an in vitro study. VPA is a candidate drug for inhibiting late-onset progressive hereditary hearing loss from the KCNQ4 p.W276S variant.

PMID:36982769 | DOI:10.3390/ijms24065695

SOURCE:
International journal of molecular sciences

PUBLISHER:

PMID:
pubmed:36982769

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:36982769

DOI:
10.3390/ijms24065695

DATE – PUBLISHED:
Wed, 29 Mar 2023 06:00:00 -0400

DATE – DOI:
2023-03-17T07:51:46Z

DATE – ADDED:
03/29/23 07:02AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/36982769/

LINK – DOI:
https://doi.org/10.3390/ijms24065695

LINK – PUBLISHER:
https://www.mdpi.com/1422-0067/24/6/5695?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-03-29T11:02:49+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
AAV-Net1 facilitates the trans-differentiation of supporting cells into hair cells in the murine cochlea

CONTENT:
Cell Mol Life Sci. 2023 Mar 14;80(4):86. doi: 10.1007/s00018-023-04743-6.

ABSTRACT

Mechanosensitive hair cells (HCs) in the cochlear sensory epithelium are critical for sound detection and transduction. Mammalian HCs in the cochlea undergo cytogenesis during embryonic development, and irreversible damage to hair cells postnatally is a major cause of deafness. During the development of the organ of Corti, HCs and supporting cells (SCs) originate from the same precursors. In the neonatal cochlea, damage to HCs activates adjacent SCs to act as HC precursors and to differentiate into new HCs. However, the plasticity of SCs to produce new HCs is gradually lost with cochlear development. Here, we delineate an essential role for the guanine nucleotide exchange factor Net1 in SC trans-differentiation into HCs. Net1 overexpression mediated by AAV-ie in SCs promoted cochlear organoid formation and HC differentiation under two and three-dimensional culture conditions. Also, AAV-Net1 enhanced SC proliferation in Lgr5-EGFPCreERT2 mice and HC generation as indicated by lineage tracing of HCs in the cochleae of Lgr5-EGFPCreERT2 /Rosa26-tdTomatoloxp/loxp mice. We further found that the up-regulation of Wnt/β-catenin and Notch signaling in AAV-Net1-transduced cochleae might be responsible for the SC proliferation and HC differentiation. Also, Net1 overexpression in SCs enhanced SC proliferation and HC regeneration and survival after HC damage by neomycin. Taken together, our study suggests that Net1 might serve as a potential target for HC regeneration and that AAV-mediated gene regulation may be a promising approach in stem cell-based therapy in hearing restoration.

PMID:36917323 | DOI:10.1007/s00018-023-04743-6

SOURCE:
Cellular and molecular life sciences : CMLS

PUBLISHER:

PMID:
pubmed:36917323

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:36917323

DOI:
10.1007/s00018-023-04743-6

DATE – PUBLISHED:
Tue, 14 Mar 2023 06:00:00 -0400

DATE – DOI:
2023-03-14T07:10:47Z

DATE – ADDED:
03/14/23 06:57PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/36917323/

LINK – DOI:
https://doi.org/10.1007/s00018-023-04743-6

LINK – PUBLISHER:
https://link.springer.com/10.1007/s00018-023-04743-6?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-03-14T22:57:54+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
The NLRP3 inflammasome as a target for sensorineural hearing loss

CONTENT:
Clin Immunol. 2023 Mar 10:109287. doi: 10.1016/j.clim.2023.109287. Online ahead of print.

ABSTRACT

Sensorineural hearing loss is the most common type of hearing loss in adults and occurs due to damage of the inner ear caused by a range of factors including ageing, excessive noise, toxins, and cancer. Auto-inflammatory disease is also a cause of hearing loss and there is evidence that inflammation could contribute to hearing loss in other conditions. Within the inner ear there are resident macrophage cells that respond to insults and whose activation correlates with damage. The NLRP3 inflammasome is a multi-molecular pro-inflammatory protein complex that forms in activated macrophages and may contribute to hearing loss. The aim of this article is to discuss the evidence for the NLRP3 inflammasome and associated cytokines as potential therapeutic targets for sensorineural hearing loss in conditions ranging from auto-inflammatory disease to tumour-induced hearing loss in vestibular schwannoma.

PMID:36907540 | DOI:10.1016/j.clim.2023.109287

SOURCE:
Clinical immunology (Orlando, Fla.)

PUBLISHER:

PMID:
pubmed:36907540

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:36907540

DOI:
10.1016/j.clim.2023.109287

DATE – PUBLISHED:
Sun, 12 Mar 2023 06:00:00 -0400

DATE – DOI:
2023-03-11T15:57:27Z

DATE – ADDED:
03/13/23 12:38AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/36907540/

LINK – DOI:
https://doi.org/10.1016/j.clim.2023.109287

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S1521661623000669?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-03-13T04:38:08+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Generation of p27icreER transgenic mice: A tool for inducible gene expression in supporting cells in the cochlea

CONTENT:
Hear Res. 2023 Mar 4;431:108727. doi: 10.1016/j.heares.2023.108727. Online ahead of print.

ABSTRACT

The loss of cochlear hair cells (HCs) is an important cause of sensorineural hearing loss, and finding ways to regenerate HCs would be the ideal way forward for restoring hearing. In this research field, tamoxifen-inducible Cre recombinase (iCreER) transgenic mice and the Cre-loxp system are widely used to manipulate gene expression in supporting cells (SCs), which lie beneath the sensory HCs and are a natural source for HC regeneration. However, many iCreER transgenic lines are of limited utility because they cannot target all subtypes of SCs or they cannot be used in the adult stage. In this study, a new line of iCreER transgenic mice, the p27-P2A-iCreERT2 knock-in mouse strain, was generated by inserting the P2A-iCreERT2 cassette immediately in front of the stop codon of p27, which kept the endogenous expression and function of p27 intact. Using a reporter mouse line with tdTomato fluorescence, we showed that the p27iCreER transgenic line can target all subtypes of cochlear SCs, including Claudius cells. p27-CreER activity in SCs was observed in both the postnatal and the adult stage, suggesting that this mouse strain can be useful for research work in adult cochlear HC regeneration. We then overexpressed Gfi1, Pou4f3, and Atoh1 in p27+ SCs of P6/7 mice using this strain and successfully induced many new Myo7a/tdTomato double-positive cells, further confirming that the p27-P2A-iCreERT2 mouse strain is a new and reliable tool for cochlear HC regeneration and hearing restoration.

PMID:36905855 | DOI:10.1016/j.heares.2023.108727

SOURCE:
Hearing research

PUBLISHER:

PMID:
pubmed:36905855

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:36905855

DOI:
10.1016/j.heares.2023.108727

DATE – PUBLISHED:
Sat, 11 Mar 2023 06:00:00 -0500

DATE – DOI:
2023-03-04T01:28:37Z

DATE – ADDED:
03/12/23 12:59AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/36905855/

LINK – DOI:
https://doi.org/10.1016/j.heares.2023.108727

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S0378595523000394?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-03-12T05:59:54+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
The Dual Roles of Triiodothyronine in Regulating the Morphology of Hair Cells and Supporting Cells during Critical Periods of Mouse Cochlear Development

CONTENT:
Int J Mol Sci. 2023 Feb 25;24(5):4559. doi: 10.3390/ijms24054559.

ABSTRACT

Clinically, thyroid-related diseases such as endemic iodine deficiency and congenital hypothyroidism are associated with hearing loss, suggesting that thyroid hormones are essential for the development of normal hearing. Triiodothyronine (T3) is the main active form of thyroid hormone and its effect on the remodeling of the organ of Corti remain unclear. This study aims to explore the effect and mechanism of T3 on the remodeling of the organ of Corti and supporting cells development during early development. In this study, mice treated with T3 at postnatal (P) day 0 or P1 showed severe hearing loss with disordered stereocilia of the outer hair cells (OHCs) and impaired function of mechanoelectrical transduction of OHCs. In addition, we found that treatment with T3 at P0 or P1 resulted in the overproduction of Deiter-like cells. Compared with the control group, the transcription levels of Sox2 and notch pathway-related genes in the cochlea of the T3 group were significantly downregulated. Furthermore, Sox2-haploinsufficient mice treated with T3 not only showed excess numbers of Deiter-like cells but also a large number of ectopic outer pillar cells (OPCs). Our study provides new evidence for the dual roles of T3 in regulating both hair cells and supporting cell development, suggesting that it is possible to increase the reserve of supporting cells.

PMID:36901990 | PMC:PMC10003541 | DOI:10.3390/ijms24054559

SOURCE:
International journal of molecular sciences

PUBLISHER:

PMID:
pubmed:36901990

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:36901990

DOI:
10.3390/ijms24054559

DATE – PUBLISHED:
Sat, 11 Mar 2023 06:00:00 -0500

DATE – DOI:
2023-02-27T08:36:41Z

DATE – ADDED:
03/14/23 07:00AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/36901990/

LINK – DOI:
https://doi.org/10.3390/ijms24054559

LINK – PUBLISHER:
https://www.mdpi.com/1422-0067/24/5/4559?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-03-14T11:00:52+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
CRISPR-mediated RNA base editing: a promising strategy to rescue deafness

CONTENT:
Signal Transduct Target Ther. 2023 Feb 27;8(1):83. doi: 10.1038/s41392-023-01349-z.

NO ABSTRACT

PMID:36849547 | PMC:PMC9969033 | DOI:10.1038/s41392-023-01349-z

SOURCE:
Signal transduction and targeted therapy

PUBLISHER:

PMID:
pubmed:36849547

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:36849547

DOI:
10.1038/s41392-023-01349-z

DATE – PUBLISHED:
Mon, 27 Feb 2023 06:00:00 -0500

DATE – DOI:
2023-02-27T05:02:40Z

DATE – ADDED:
03/01/23 07:02AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/36849547/

LINK – DOI:
https://doi.org/10.1038/s41392-023-01349-z

LINK – PUBLISHER:
https://www.nature.com/articles/s41392-023-01349-z?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-03-01T12:02:19+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Potentials and limitations of pharmaceutical and pharmacological applications of bile acids in hearing loss treatment

CONTENT:
Ther Deliv. 2023 Feb 21. doi: 10.4155/tde-2022-0033. Online ahead of print.

ABSTRACT

Hearing loss is a worldwide epidemic, with approximately 1.5 billion people currently struggling with hearing-related conditions. Currently, the most wildly used and effective treatments for hearing loss are primarily focus on the use of hearing aids and cochlear implants. However, these have many limitations, highlighting the importance of developing a pharmacological solution that may be used to overcome barriers associated with such devices. Due to the challenges of delivering therapeutic agents to the inner ear, bile acids are being explored as potential drug excipients and permeation enhancers. This review, therefore, aims to explore the pathophysiology of hearing loss, the challenges in treatment and the manners in which bile acids could potentially aid in overcoming these challenges.

PMID:36803017 | DOI:10.4155/tde-2022-0033

SOURCE:
Therapeutic delivery

PUBLISHER:

PMID:
pubmed:36803017

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:36803017

DOI:
10.4155/tde-2022-0033

DATE – PUBLISHED:
Tue, 21 Feb 2023 06:00:00 -0500

DATE – DOI:
2023-02-21T09:13:15Z

DATE – ADDED:
02/21/23 07:10PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/36803017/

LINK – DOI:
https://doi.org/10.4155/tde-2022-0033

LINK – PUBLISHER:
https://www.future-science.com/doi/10.4155/tde-2022-0033?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-02-22T00:10:22+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Oridonin employs interleukin 1 receptor type 2 to treat noise-induced hearing loss by blocking inner ear inflammation

CONTENT:
Biochem Pharmacol. 2023 Feb 16:115457. doi: 10.1016/j.bcp.2023.115457. Online ahead of print.

ABSTRACT

NOD-like receptor protein 3 (NLRP3) inflammasomes trigger the inflammatory cascades and participate in various inflammatory diseases, including noise-induced hearing loss (NIHL) caused by oxidative stress. Recently, the anti-inflammatory traditional medicine oridonin (Ori) has been reported to provide hearing protection in mice after noise exposure by blocking the NLRP3-never in mitosis gene A-related kinase 7 (NEK7)-inflammasome complex assembly. Using RNA sequencing analysis, we further elucidated that interleukin 1 receptor type 2 (IL1R2) may be another crucial factor regulated by Ori to protect NIHL. We observed that IL1R2 expression was localized in spiral ganglion neurons, inner and outer hair cells, in Ori-treated mouse cochleae. Additionally, we confirmed that ectopic overexpression of IL1R2 in the inner ears of healthy mice using an adeno-associated virus delivery system significantly reduced noise-induced ribbon synapse lesions and hearing loss by blocking the “cytokine storm” in the inner ear. This study provides a novel theoretical foundation for guiding the clinical treatment of NIHL.

PMID:36806583 | DOI:10.1016/j.bcp.2023.115457

SOURCE:
Biochemical pharmacology

PUBLISHER:

PMID:
pubmed:36806583

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:36806583

DOI:
10.1016/j.bcp.2023.115457

DATE – PUBLISHED:
Wed, 22 Feb 2023 06:00:00 -0500

DATE – DOI:
2023-02-16T16:47:39Z

DATE – ADDED:
02/22/23 01:02PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/36806583/

LINK – DOI:
https://doi.org/10.1016/j.bcp.2023.115457

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S0006295223000485?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-02-22T18:02:56+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Promoting TFEB nuclear localization with curcumin analog C1 attenuates sensory hair cell injury and delays age-related hearing loss in C57BL/6 mice

CONTENT:
Neurotoxicology. 2023 Feb 13:S0161-813X(23)00024-4. doi: 10.1016/j.neuro.2023.02.004. Online ahead of print.

ABSTRACT

Sensory hair cell (HC) injuries, especially outer hair cell (OHC) loss, are well-documented to be the primary pathology of age-related hearing loss (AHL). Recent studies have demonstrated that autophagy plays an important role in HC injury in the inner ear. In our previous works, a decline in autophagy levels and HC loss were found to occur simultaneously in the inner ears of aged C57BL/6 mice, and the administration of rapamycin promoted autophagy levels, which reduced OHC loss and delayed AHL, but the underlying mechanism of autophagy in AHL has not been well elucidated. Transcription factor EB (TFEB), an autophagy regulator and the downstream target of mammalian target of rapamycin (mTOR), is involved in the pathological development of neurodegenerative disease. This study would address the link between autophagy and TFEB in aged C57BL/6 mouse cochleae and clarify the effect of the TFEB activator curcumin analog C1 (C1) in aged cochleae. Decreased TFEB nuclear localization (p = 0.0371) and autophagy dysfunction (p = 0.0273) were observed in the cochleae of aged C57BL/6 mice that exhibited AHL, HCs loss and HCs senescence. Treatment with C1 promoted TFEB nuclear localization and restored autophagy, subsequently alleviating HC injury and delaying AHL. The protective effect of C1 on HEI-OC1 cells against autophagy disorder and aging induced by D-galactose was abolished by chloroquine, which is one of the commonly used autophagy inhibitors. Overall, our results demonstrated that the capacity to perform autophagy is mediated by the nuclear localization of TFEB in aged C57BL/6 mouse cochleae. C1 promotes the nuclear localization of TFEB, subsequently alleviating HC injury and delaying AHL by restoring the impaired autophagy function. TFEB may serve as a new therapeutic target for AHL treatment.

PMID:36792013 | DOI:10.1016/j.neuro.2023.02.004

SOURCE:
Neurotoxicology

PUBLISHER:

PMID:
pubmed:36792013

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:36792013

DOI:
10.1016/j.neuro.2023.02.004

DATE – PUBLISHED:
Wed, 15 Feb 2023 06:00:00 -0500

DATE – DOI:
2023-02-14T02:03:43Z

DATE – ADDED:
02/16/23 01:02AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/36792013/

LINK – DOI:
https://doi.org/10.1016/j.neuro.2023.02.004

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S0161813X23000244?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-02-16T06:02:18+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Novel WFS1 mutations in patients with low-to-middle frequency hearing loss

CONTENT:
Int J Pediatr Otorhinolaryngol. 2023 Feb 9;167:111484. doi: 10.1016/j.ijporl.2023.111484. Online ahead of print.

ABSTRACT

BACKGROUND: Hearing loss (HL) is the most common sensorineural disorder in human. It is estimated that genetic factors contribute to over 50% of prelingual hearing loss. Most of dominant HHL patients manifest postlingual progressive hearing loss that mainly affect high frequencies. However, mutations in a few dominant HL genes, such as WFS1, TECTA and DIAPH1, cause distinct audiogram that primarily affects the low and middle frequencies.

METHODS: We recruited twelve independent HL families with worse low or middle frequency audiograms. Each proband of these families was excluded for pathogenic mutations in GJB2, SLC26A4, and MT-RNR1 genes. Mutation screening was performed by whole exome sequencing. Next, candidate variants were validated in each family by sanger sequencing.

RESULTS: Six heterozygous WFS1 variants were identified in six families, including three novel mutations (c.2519T > G, p.F840C; c.2048T > G, p.M683R and c.2419A > C, p.S807R) and three previously reported variants (c.2005T > C, p.Y669H; c.2590G > A, p.E864K and c.G2389A, p.D797 N). All the novel mutations were absent in 100 ethnically matched controls and were predicted to be deleterious by multiple algorithms.

CONCLUSIONS: We identified three novel and three previously reported WFS1 mutations in six unrelated Chinese families. Our findings enriched the genotype-phenotype spectrum of WFS1 related NSHL. Additional genotype-phenotype correlation study will clarify the detailed phenotypic range caused by WFS1 mutations.

PMID:36958120 | DOI:10.1016/j.ijporl.2023.111484

SOURCE:
International journal of pediatric otorhinolaryngology

PUBLISHER:

PMID:
pubmed:36958120

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:36958120

DOI:
10.1016/j.ijporl.2023.111484

DATE – PUBLISHED:
Thu, 23 Mar 2023 06:00:00 -0400

DATE – DOI:
2023-02-09T07:56:04Z

DATE – ADDED:
03/24/23 01:00AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/36958120/

LINK – DOI:
https://doi.org/10.1016/j.ijporl.2023.111484

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S0165587623000502?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-03-24T05:00:48+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Advances in gene therapy hold promise for treating hereditary hearing loss

CONTENT:
Mol Ther. 2023 Feb 7:S1525-0016(23)00064-3. doi: 10.1016/j.ymthe.2023.02.001. Online ahead of print.

ABSTRACT

Gene therapy focuses on genetic modification to produce therapeutic effects or treat diseases by repairing or reconstructing genetic material, thus being expected to be the most promising therapeutic strategy for genetic disorders. Due to the growing attention to hearing impairment, an increasing amount of research is attempting to utilize gene therapy for hereditary hearing loss (HHL)-an important monogenic disease and the most common type of congenital deafness. Several gene therapy clinical trials for HHL have recently been approved, and additionally, CRISPR/Cas tools have been attempted for HHL treatment. Therefore, in order to further advance the development of inner ear gene therapy and promote its broad application in other forms of genetic disease, it is imperative to review the progress of gene therapy for HHL. Herein, we address three main gene therapy strategies-gene replacement, gene suppression, and gene editing, summarizing which strategy is most appropriate for particular monogenic diseases based on different pathogenic mechanisms and then focusing on their successful applications for HHL in preclinical trials. Finally, we elaborate on the challenges and outlooks of gene therapy for HHL.

PMID:36755494 | DOI:10.1016/j.ymthe.2023.02.001

SOURCE:
Molecular therapy : the journal of the American Society of Gene Therapy

PUBLISHER:

PMID:
pubmed:36755494

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:36755494

DOI:
10.1016/j.ymthe.2023.02.001

DATE – PUBLISHED:
Thu, 09 Feb 2023 06:00:00 -0500

DATE – DOI:
2023-02-08T07:21:26Z

DATE – ADDED:
02/09/23 07:00AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/36755494/

LINK – DOI:
https://doi.org/10.1016/j.ymthe.2023.02.001

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S1525001623000643?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2023-02-09T12:00:34+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Downregulation of Cav3.1 T-type Calcium Channel Expression in Age-related Hearing Loss Model

CONTENT:
Curr Med Sci. 2021 Aug;41(4):680-686. doi: 10.1007/s11596-021-2416-0. Epub 2021 Aug 17.

ABSTRACT

OBJECTIVE: Age-related hearing loss (AHL), characterized by degeneration of cochlea structures, is the most common sensory disorder among the elderly worldwide. The calcium channel is considered to contribute to normal hearing. However, the role of the T-type voltage-activated calcium channel, Cav3.1, remains unclear in AHL. Here, we investigate the age-related change of Cav3.1 expression in the cochlea and D-gal-induced senescent HEI-OC1 cells.

METHODS: Cochleae from C57BL/6 mice at 2 months and 12 months of age were assessed. Senescence in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells was induced by D-gal treatment. The immunofluorescence technique was employed to investigate the distribution of Cav3.1 in vivo and in vitro. Quantitative assessment was achieved by Western blotting and real-time PCR.

RESULTS: In comparison with 2-month-old animals, 12-month old C57BL/6 mice exhibited great loss of hair cells and elevated auditory brainstem threshold. The Cav3.1 was located in hair cells, spiral ganglion cells, lateral walls, and the expression of Cav3.1 protein and mRNA decreased in the aged cochleae. D-gal-induced senescence assay confirmed the down-regulation of Cav3.1 expression in senescent HEI-OC1 cells.

CONCLUSION: Our results show that age-related down-regulated expression of Cav3.1 in the cochleae is associated with AHL and may contribute to the pathogenesis of AHL.

PMID:34403092 | DOI:10.1007/s11596-021-2416-0

SOURCE:
Current medical science

PUBLISHER:

PMID:
pubmed:34403092

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:34403092

DOI:
10.1007/s11596-021-2416-0

DATE – PUBLISHED:
Tue, 17 Aug 2021 06:00:00 -0400

DATE – DOI:
2021-08-17T10:36:41Z

DATE – ADDED:
08/17/21 07:00PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/34403092/

LINK – DOI:
https://doi.org/10.1007/s11596-021-2416-0

LINK – PUBLISHER:
https://link.springer.com/10.1007/s11596-021-2416-0?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-08-17T23:00:52+00:00, https://www.hearinglosstreatmentreport.com.

https://www.sciencedirect.com/science/article/abs/pii/S1534580721005591?via%3Dihub

Enhancer decommissioning imposes an epigenetic barrier to sensory hair cell regeneration

https://www.cell.com/molecular-therapy-family/molecular-therapy/pdf/S1525-0016(21)00367-1.pdf

https://www.frontiersin.org/articles/10.3389/fncel.2021.666706/full

https://www.hindawi.com/journals/np/2021/4784385/

Noise-Induced Hearing Loss: Updates on Molecular Targets and Potential Interventions

Reestablishing Neural Plasticity in Regenerated Spiral Ganglion Neurons and Sensory Hair Cells for Hearing Loss

CATEGORY:
Research

SCREENSHOT:

TITLE:
mTOR Signaling in the Inner Ear as Potential Target to Treat Hearing Loss

CONTENT:
Int J Mol Sci. 2021 Jun 14;22(12):6368. doi: 10.3390/ijms22126368.

ABSTRACT

Hearing loss affects many people worldwide and occurs often as a result of age, ototoxic drugs and/or excessive noise exposure. With a growing number of elderly people, the number of people suffering from hearing loss will also increase in the future. Despite the high number of affected people, for most patients there is no curative therapy for hearing loss and hearing aids or cochlea implants remain the only option. Important treatment approaches for hearing loss include the development of regenerative therapies or the inhibition of cell death/promotion of cell survival pathways. The mammalian target of rapamycin (mTOR) pathway is a central regulator of cell growth, is involved in cell survival, and has been shown to be implicated in many age-related diseases. In the inner ear, mTOR signaling has also started to gain attention recently. In this review, we will emphasize recent discoveries of mTOR signaling in the inner ear and discuss implications for possible treatments for hearing restoration.

PMID:34198685 | DOI:10.3390/ijms22126368

SOURCE:
International journal of molecular sciences

PUBLISHER:

PMID:
pubmed:34198685

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:34198685

DOI:
10.3390/ijms22126368

DATE – PUBLISHED:
Fri, 02 Jul 2021 06:00:00 -0400

DATE – DOI:
2021-06-15T02:31:04Z

DATE – ADDED:
07/02/21 08:07AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/34198685/

LINK – DOI:
https://doi.org/10.3390/ijms22126368

LINK – PUBLISHER:
https://www.mdpi.com/1422-0067/22/12/6368?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-07-02T12:07:25+00:00, https://www.hearinglosstreatmentreport.com.

https://www.jneurosci.org/content/early/2021/04/19/JNEUROSCI.3238-20.2021

Research Articles, Systems/Circuits
Primary Neural Degeneration in Noise-Exposed Human Cochleas: Correlations with Outer Hair Cell Loss and Word-Discrimination Scores

Journal of Neuroscience 21 April 2021, JN-RM-3238-20; DOI: https://doi.org/10.1523/JNEUROSCI.3238-20.2021

Abstract
Animal studies suggest that cochlear nerve degeneration precedes sensory cell degeneration in both noise-induced hearing loss (NIHL) and age-related hearing loss (ARHL), producing a hearing impairment that is not reflected in audiometric thresholds. Here, we investigated the histopathology of human ARHL and NIHL by comparing loss of auditory nerve fibers (ANFs), cochlear hair cells and the stria vascularis in a group of 52 cases with noise-exposure history against an age-matched control group. Although strial atrophy increased with age, there was no effect of noise history. Outer hair cell (OHC) loss also increased with age throughout the cochlea but was unaffected by noise history in the low-frequency region (<2 kHz), while greatly exacerbated at high frequencies (≥2 kHz). Inner hair cell (IHC) loss was primarily seen at high frequencies but was unaffected by noise at either low or high frequencies. ANF loss was substantial at all cochlear frequencies and was exacerbated by noise throughout. According to a multivariable regression model, this loss of neural channels contributes to poor word discrimination among those with similar audiometric threshold losses. The histopathological patterns observed also suggest that, whereas the low-frequency OHC loss may be an unavoidable consequence of aging, the high-frequency loss, which produces the classic down-sloping audiogram of ARHL, may be partially because of avoidable ear abuse, even among those without a documented history of acoustic overexposure. Statement of Significance As regenerative therapeutics in sensorineural hearing loss enter clinical trials, it becomes critical to infer which cochlear pathologies are present in addition to hair cell loss. Here, by analyzing human autopsy material, we show that acoustic injury accelerates age-related primary neural degeneration, but not strial degeneration, neither of which can be inferred from audiometric thresholds. It exacerbates outer hair cell (OHC) loss only in the high-frequency half of the cochlea, suggesting that the apical loss is age-related, whereas the basal loss is partially noise induced, and therefore avoidable. Statistical analysis suggests that neural loss helps explain differences in word-recognition ability among individuals with similar audiometric thresholds. The surprising correlation between neural loss and OHC loss in the cochlea’s speech region also implicates neural loss in the well-known decline in word scores as thresholds deteriorate with age. Custom Title Primary Neural Degeneration in Noise-Exposed Human Cochleas: Implications for Regenerative Therapeutics

CATEGORY:
Research

SCREENSHOT:

TITLE:
Congenital Deafness and Recent Advances Towards Restoring Hearing Loss

CONTENT:
Curr Protoc. 2021 Mar;1(3):e76. doi: 10.1002/cpz1.76.

ABSTRACT

Congenital hearing loss is the most common birth defect, estimated to affect 2-3 in every 1000 births. Currently there is no cure for hearing loss. Treatment options are limited to hearing aids for mild and moderate cases, and cochlear implants for severe and profound hearing loss. Here we provide a literature overview of the environmental and genetic causes of congenital hearing loss, common animal models and methods used for hearing research, as well as recent advances towards developing therapies to treat congenital deafness. © 2021 The Authors.

PMID:33780161 | DOI:10.1002/cpz1.76

SOURCE:
Current protocols

PUBLISHER:

PMID:
pubmed:33780161

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33780161

DOI:
10.1002/cpz1.76

DATE – PUBLISHED:
Mon, 29 Mar 2021 06:00:00 -0400

DATE – DOI:
2021-03-29T13:07:03Z

DATE – ADDED:
03/30/21 12:08AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33780161/

LINK – DOI:
https://doi.org/10.1002/cpz1.76

LINK – PUBLISHER:
https://onlinelibrary.wiley.com/doi/10.1002/cpz1.76?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-30T04:08:44+00:00, https://www.hearinglosstreatmentreport.com.