Research

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:
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.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Expression of serum proteins in noise induced hearing loss workers of mining based industry

CONTENT:
J Proteomics. 2021 Mar 15:104185. doi: 10.1016/j.jprot.2021.104185. Online ahead of print.

ABSTRACT

Noise Induced Hearing Loss (NIHL) is caused by excessive noise exposure due to occupational activities thus affects communication and quality of life. Prolonged occupational and environmental exposure to loud noise damages key molecules present in the micro-machinery of the ear which are required for the mechano-electrical transduction of sound waves in cochlea. Specific proteins are known to be associated with hearing loss and related structural and functional disabilities in the human inner, outer hair cells and cochlea. Rationale of this study was to identify the cochlear proteins associated with the pathophysiology of NIHL using proteomic approaches in mining based industrial workers. Total (n = 210) samples were collected from mining based industrial workers of central India. Subjects were categorized based on audiometric analysis. Proteome changes of the host serum were investigated using one and two-dimensional electrophoresis in combination with LC-MS/MS and MALDI-TOF MS. Up-regulated 46 cochlear proteins among confirmed NIHL cases were identified by MASCOT. Shrinkage discriminant analysis provided top 25 discriminating feature proteins namely myosin, transthyretin, SERPIN, CCDC50, enkurin, transferin etc. The identified potential proteins may be used as biomarkers for early detection and to understand the pathogenic mechanism of NIHL. Evaluation of these biomarkers in follow-up cases may further aid in improving NIHL diagnosis. SIGNIFICANCE: Human proteome study in Noise Induced Hearing Loss (NIHL) cases has not been published till date. This study represents most comprehensive proteomic analysis in NIHL cases taken from Indian mine workers. The identified key twenty-five discriminating feature proteins which are upregulated when an individual develops (or is in stage of development of) NIHL, provides insights into the potential roles of these varied proteins in disease progression. The proteins thus identified by proteomic approach may be used as early diagnostic biomarker to predict the occurrence of disease at very early stage.

PMID:33737237 | DOI:10.1016/j.jprot.2021.104185

SOURCE:
Journal of proteomics

PUBLISHER:

PMID:
pubmed:33737237

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33737237

DOI:
10.1016/j.jprot.2021.104185

DATE – PUBLISHED:
Fri, 19 Mar 2021 06:00:00 -0400

DATE – DOI:
2021-03-18T20:32:33Z

DATE – ADDED:
03/19/21 03:00PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33737237/

LINK – DOI:
https://doi.org/10.1016/j.jprot.2021.104185

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S1874391921000841?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-19T19:00:02+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
T2 relaxation time shortening in the cochlea of patients with sudden sensory neuronal hearing loss: a retrospective study using quantitative synthetic magnetic resonance imaging

CONTENT:
Eur Radiol. 2021 Feb 20. doi: 10.1007/s00330-021-07749-5. Online ahead of print.

ABSTRACT

OBJECTIVES: High cochlear signal intensity on three-dimensional (3D) T2 fluid-attenuated inversion recovery (FLAIR) sequences in patients with sudden sensorineural hearing loss (SSNHL) has been reported. Here, we evaluated the cochlear T2 relaxation time differences in patients with idiopathic SSNHL using quantitative synthetic MRI (SyMRI).

METHODS: Twenty-four patients with unilateral SSNHL who underwent precontrast conventional 3D FLAIR and SyMRI were retrospectively included. T1 and T2 relaxation times and the proton density (PD) of the bilateral ears were measured by manually drawn regions of interest. Wilcoxon signed-rank tests and intra- and interobserver correlation analyses were performed. Qualitative analysis was also performed to determine the presence and laterality of the asymmetric high signal intensity on synthetic FLAIR (SyFLAIR) images.

RESULTS: The T2 relaxation time was significantly lower in the affected (basal and apico-middle turns) than in the unaffected cochlea (basal turn: 519 ± 181.3 vs. 608.8 ± 203.6, p = 0.042; apico-middle turn: 410.8 ± 163.8 vs. 514.5 ± 186.3, p = 0.037). There were no significant differences in the T1 relaxation time and PD between the affected and unaffected ears (p > 0.05). Additionally, three patients without asymmetric signal intensity on conventional MRI showed asymmetric increased signal intensity in the affected ear on SyFLAIR.

CONCLUSIONS: The T2 relaxation time was significantly shorter in the affected than in the unaffected cochlea of patients with idiopathic SSNHL. The SyMRI-derived T2 relaxation time may be a promising imaging marker, suggesting that the changes in inner ear fluid composition are implicated in the idiopathic SSNHL development.

KEY POINTS: • T2 relaxation time was significantly lower in the affected than in the unaffected cochlea. • SyFLAIR showed increased lesion conspicuity compared to conventional 3D-FLAIR in detecting asymmetric high signal intensity of the affected side. • SyMRI-derived T2 relaxation time may be a promising imaging marker of the affected ear in patients with idiopathic SSNHL.

PMID:33609144 | DOI:10.1007/s00330-021-07749-5

SOURCE:
European radiology

PUBLISHER:

PMID:
pubmed:33609144

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33609144

DOI:
10.1007/s00330-021-07749-5

DATE – PUBLISHED:
Sat, 20 Feb 2021 06:00:00 -0500

DATE – DOI:
2021-02-20T17:19:51Z

DATE – ADDED:
02/21/21 01:27AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33609144/

LINK – DOI:
https://doi.org/10.1007/s00330-021-07749-5

LINK – PUBLISHER:
http://link.springer.com/10.1007/s00330-021-07749-5

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-02-21T06:27:26+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Sudden Sensorineural Hearing Loss: A Diagnostic and Therapeutic Emergency

CONTENT:
J Am Board Fam Med. 2021 Jan-Feb;34(1):216-223. doi: 10.3122/jabfm.2021.01.200199.

ABSTRACT

The family physician’s role in recognizing and managing sudden sensorineural hearing loss (SSNHL) is crucial. A recently updated otolaryngologic clinical practice guideline has been released for this emergency syndrome, but dissemination is limited to a specialty journal. As a result, the guidelines may not be widely available in the primary care setting where patients often present. We provide this focused review to clarify and disseminate SSNHL guidelines for the frontline family physician.

PMID:33452100 | DOI:10.3122/jabfm.2021.01.200199

SOURCE:
Journal of the American Board of Family Medicine : JABFM

PUBLISHER:

PMID:
pubmed:33452100

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33452100

DOI:
10.3122/jabfm.2021.01.200199

DATE – PUBLISHED:
Sat, 16 Jan 2021 06:00:00 -0500

DATE – DOI:
2021-01-15T16:05:21Z

DATE – ADDED:
01/17/21 02:22AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33452100/

LINK – DOI:
https://doi.org/10.3122/jabfm.2021.01.200199

LINK – PUBLISHER:
http://www.jabfm.org/lookup/doi/10.3122/jabfm.2021.01.200199

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-01-17T07:22:43+00:00, https://www.hearinglosstreatmentreport.com.

https://www.nature.com/articles/s41598-020-79946-z

Steady streaming as a method for drug delivery to the inner ear

https://www.mdpi.com/1422-0067/22/1/131/htm

https://pubmed.ncbi.nlm.nih.gov/33374462/

Molecular Aspects of the Development and Function of Auditory Neurons

CATEGORY:
Research

SCREENSHOT:

TITLE:
Weakening of Interaction Networks with Aging in Tip-Link Protein Induces Hearing Loss

CONTENT:
Biochem J. 2020 Dec 3:BCJ20200799. doi: 10.1042/BCJ20200799. Online ahead of print.

ABSTRACT

Age-related hearing loss (ARHL) is a common condition in humans marking the gradual decrease in hearing with age. Perturbations in the tip-link protein cadherin-23 that absorbs the mechanical tension from sound and maintains the integrity of hearing is associated with ARHL. Here, in search of molecular origins for ARHL, we dissect the conformational behavior of cadherin-23 along with the mutant S47P that progresses the hearing-loss drastically. Using an array of experimental and computational approaches, we highlight a lower thermodynamic stability, significant weakening in the hydrogen-bond network and inter-residue correlations among β-strands, due to the S47P mutation. The loss in correlated motions translates to not only a remarkable two orders of magnitude slower folding in the mutant but also to a proportionately complex unfolding mechanism. We thus propose that loss in correlated motions within cadherin-23 with aging may trigger ARHL, a molecular feature that likely holds true for other disease-mutations in β-strand-rich proteins.

PMID:33270084 | DOI:10.1042/BCJ20200799

SOURCE:
The Biochemical journal

PUBLISHER:

PMID:
pubmed:33270084

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33270084

DOI:
10.1042/BCJ20200799

DATE – PUBLISHED:
Thu, 03 Dec 2020 06:00:00 -0500

DATE – DOI:
2020-12-03T14:31:41Z

DATE – ADDED:
12/03/20 08:09PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33270084/

LINK – DOI:
https://doi.org/10.1042/BCJ20200799

LINK – PUBLISHER:
https://portlandpress.com/biochemj/article/doi/10.1042/BCJ20200799/227128/Weakening-of-Interaction-Networks-with-Aging-in

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-04T01:09:05+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
BRAF inhibition protects against hearing loss in mice

CONTENT:
Sci Adv. 2020 Dec 2;6(49):eabd0561. doi: 10.1126/sciadv.abd0561. Print 2020 Dec.

ABSTRACT

Hearing loss caused by noise, aging, antibiotics, and chemotherapy affects 10% of the world population, yet there are no Food and Drug Administration (FDA)-approved drugs to prevent it. Here, we screened 162 small-molecule kinase-specific inhibitors for reduction of cisplatin toxicity in an inner ear cell line and identified dabrafenib (TAFINLAR), a BRAF kinase inhibitor FDA-approved for cancer treatment. Dabrafenib and six additional kinase inhibitors in the BRAF/MEK/ERK cellular pathway mitigated cisplatin-induced hair cell death in the cell line and mouse cochlear explants. In adult mice, oral delivery of dabrafenib repressed ERK phosphorylation in cochlear cells, and protected from cisplatin- and noise-induced hearing loss. Full protection was achieved in mice with co-treatment with oral AZD5438, a CDK2 kinase inhibitor. Our study explores a previously unidentified cellular pathway and molecular target BRAF kinase for otoprotection and may advance dabrafenib into clinics to benefit patients with cisplatin- and noise-induced ototoxicity.

PMID:33268358 | DOI:10.1126/sciadv.abd0561

SOURCE:
Science advances

PUBLISHER:

PMID:
pubmed:33268358

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33268358

DOI:
10.1126/sciadv.abd0561

DATE – PUBLISHED:
Thu, 03 Dec 2020 06:00:00 -0500

DATE – DOI:
2020-12-03T02:03:28Z

DATE – ADDED:
12/03/20 07:55AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33268358/

LINK – DOI:
https://doi.org/10.1126/sciadv.abd0561

LINK – PUBLISHER:
https://advances.sciencemag.org/lookup/doi/10.1126/sciadv.abd0561

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-03T12:55:04+00:00, https://www.hearinglosstreatmentreport.com.

CATEGORY:
Research

SCREENSHOT:

TITLE:
Mutations of MAP1B encoding a microtubule-associated phosphoprotein cause sensorineural hearing loss

CONTENT:
JCI Insight. 2020 Dec 3;5(23):136046. doi: 10.1172/jci.insight.136046.

ABSTRACT

The pathophysiology underlying spiral ganglion cell defect-induced deafness remains elusive. Using the whole exome sequencing approach, in combination with functional assays and a mouse disease model, we identified the potentially novel deafness-causative MAP1B gene encoding a highly conserved microtubule-associated protein. Three novel heterozygous MAP1B mutations (c.4198A>G, p.1400S>G; c.2768T>C, p.923I>T; c.5512T>C, p.1838F>L) were cosegregated with autosomal dominant inheritance of nonsyndromic sensorineural hearing loss in 3 unrelated Chinese families. Here, we show that MAP1B is highly expressed in the spiral ganglion neurons in the mouse cochlea. Using otic sensory neuron-like cells, generated by pluripotent stem cells from patients carrying the MAP1B mutation and control subject, we demonstrated that the p.1400S>G mutation caused the reduced levels and deficient phosphorylation of MAP1B, which are involved in the microtubule stability and dynamics. Strikingly, otic sensory neuron-like cells exhibited disturbed dynamics of microtubules, axonal elongation, and defects in electrophysiological properties. Dysfunctions of these derived otic sensory neuron-like cells were rescued by genetically correcting MAP1B mutation using CRISPR/Cas9 technology. Involvement of MAP1B in hearing was confirmed by audiometric evaluation of Map1b heterozygous KO mice. These mutant mice displayed late-onset progressive sensorineural hearing loss that was more pronounced in the high frequencies. The spiral ganglion neurons isolated from Map1b mutant mice exhibited the deficient phosphorylation and disturbed dynamics of microtubules. Map1b deficiency yielded defects in the morphology and electrophysiology of spiral ganglion neurons, but it did not affect the morphologies of cochlea in mice. Therefore, our data demonstrate that dysfunctions of spiral ganglion neurons induced by MAP1B deficiency caused hearing loss.

PMID:33268592 | DOI:10.1172/jci.insight.136046

SOURCE:
JCI insight

PUBLISHER:

PMID:
pubmed:33268592

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33268592

DOI:
10.1172/jci.insight.136046

DATE – PUBLISHED:
Thu, 03 Dec 2020 06:00:00 -0500

DATE – DOI:
2020-12-02T16:04:40Z

DATE – ADDED:
12/03/20 07:55AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33268592/

LINK – DOI:
https://doi.org/10.1172/jci.insight.136046

LINK – PUBLISHER:
https://insight.jci.org/articles/view/136046

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-03T12:55:03+00:00, https://www.hearinglosstreatmentreport.com.

TITLE:
Endoscopic-Assisted Drug Delivery for Inner Ear Regeneration

DESCRIPTION:
Sensorineural hearing loss is caused by irreversible loss of auditory hair cells and/or neurons and is increasing in prevalence. Hair cells and neurons do not regenerate after damage, but novel regeneration therapies based on small molecule drugs, gene therapy, and cell replacement strategies offer promising therapeutic options. Endogenous and exogenous regeneration techniques are discussed in context of their feasibility for hair cell and neuron regeneration. Gene therapy and treatment of…

CONTENT:
Otolaryngol Clin North Am . 2021 Feb;54(1):189-200. doi: 10.1016/j.otc.2020.09.022.

ABSTRACT

Sensorineural hearing loss is caused by irreversible loss of auditory hair cells and/or neurons and is increasing in prevalence. Hair cells and neurons do not regenerate after damage, but novel regeneration therapies based on small molecule drugs, gene therapy, and cell replacement strategies offer promising therapeutic options. Endogenous and exogenous regeneration techniques are discussed in context of their feasibility for hair cell and neuron regeneration. Gene therapy and treatment of synaptopathy represent promising future therapies. Minimally invasive endoscopic ear surgery offers a viable approach to aid in delivery of pharmacologic compounds, cells, or viral vectors to the inner ear for all of these techniques.

PMID:33243375 | DOI:10.1016/j.otc.2020.09.022

IDENTIFIER:
pmid:33243375,doi:10.1016/j.otc.2020.09.022

PMID:
pubmed:33243375

ID:
5aa6076e0127310720e03f8fa09545b5pubmed:33243375

DOI:
10.1016/j.otc.2020.09.022

DATE – PUBLISHED:
Fri, 27 Nov 2020 06:00:00 -0500

DATE – DOI:
2020-11-23T09:13:42Z

DATE – RETRIEVED:
11/27/20 06:17AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33243375/

LINK – DOI:
https://doi.org/10.1016/j.otc.2020.09.022

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S0030666520366962

https://www.pnas.org/content/early/2020/11/13/2016858117

Proc Natl Acad Sci U S A
2020 Nov 16;202016858. doi: 10.1073/pnas.2016858117. Online ahead of print.
Fast recovery of disrupted tip links induced by mechanical displacement of hair bundles