scholarly journals Gene therapy as a possible option to treat hereditary hearing loss

2020 ◽  
Vol 32 (2) ◽  
pp. 149-159
Author(s):  
Michael Morgan ◽  
Juliane W. Schott ◽  
Axel Rossi ◽  
Christian Landgraf ◽  
Athanasia Warnecke ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Hearing Loss ◽  
Middle Ear ◽  
Hearing Aids ◽  
Spiral Ganglion ◽  
Primary Auditory Cortex ◽  
Auditory Pathway ◽  
Therapeutic Strategies ◽  
Sound Waves ◽  
Ganglion Neurons

Abstract The process of hearing involves a series of events. The energy of sound is captured by the outer ear and further transferred through the external auditory canal to the middle ear. In the middle ear, sound waves are converted into movements of the tympanic membrane and the ossicles, thereby amplifying the pressure so that it is sufficient to cause movement of the cochlear fluid. The traveling wave within the cochlea leads to depolarization of the inner ear hair cells that, in turn, release the neurotransmitter glutamate. Thereby, the spiral ganglion neurons are activated to transfer the signals via the auditory pathway to the primary auditory cortex. This complex combination of mechanosensory and physiological mechanisms involves many distinct types of cells, the function of which are impacted by numerous proteins, including those involved in ion channel activity, signal transduction and transcription. In the last 30 years, pathogenic variants in over 150 genes were found to be linked to hearing loss. Hearing loss affects over 460 million people world-wide, and current treatment approaches, such as hearing aids and cochlear implants, serve to improve hearing capacity but do not address the underlying genetic cause of hearing loss. Therefore, therapeutic strategies designed to correct the genetic defects causative for hearing loss offer the possibility to treat these patients. In this review, we will discuss genetic causes of hearing loss, novel gene therapeutic strategies to correct hearing loss due to gene defects and some of the preclinical studies in hearing loss animal models as well as the clinical translation of gene therapy approaches to treat hearing loss patients.

scholarly journals Mechanism and Prevention of Spiral Ganglion Neuron Degeneration in the Cochlea

2022 ◽  
Vol 15 ◽  
Author(s):  
Li Zhang ◽  
Sen Chen ◽  
Yu Sun
Keyword(s):  
Gene Therapy ◽  
Hearing Loss ◽  
Stem Cell ◽  
Cell Therapy ◽  
Sensory Neurons ◽  
Stem Cell Therapy ◽  
Spiral Ganglion ◽  
Spiral Ganglion Neuron ◽  
Regeneration Ability ◽  
Ganglion Neurons

Sensorineural hearing loss (SNHL) is one of the most prevalent sensory deficits in humans, and approximately 360 million people worldwide are affected. The current treatment option for severe to profound hearing loss is cochlear implantation (CI), but its treatment efficacy is related to the survival of spiral ganglion neurons (SGNs). SGNs are the primary sensory neurons, transmitting complex acoustic information from hair cells to second-order sensory neurons in the cochlear nucleus. In mammals, SGNs have very limited regeneration ability, and SGN loss causes irreversible hearing loss. In most cases of SNHL, SGN damage is the dominant pathogenesis, and it could be caused by noise exposure, ototoxic drugs, hereditary defects, presbycusis, etc. Tremendous efforts have been made to identify novel treatments to prevent or reverse the damage to SGNs, including gene therapy and stem cell therapy. This review summarizes the major causes and the corresponding mechanisms of SGN loss and the current protection strategies, especially gene therapy and stem cell therapy, to promote the development of new therapeutic methods.

Otopathologic Abnormalities in CHARGE Syndrome

2021 ◽  
pp. 019459982110089
Author(s):  
Rafael da Costa Monsanto ◽  
Renata Malimpensa Knoll ◽  
Norma de Oliveira Penido ◽  
Grace Song ◽  
Felipe Santos ◽  
...  
Keyword(s):  
Facial Nerve ◽  
Middle Ear ◽  
Spiral Ganglion ◽  
Internal Auditory Canal ◽  
Semicircular Canals ◽  
Charge Syndrome ◽  
University Of Minnesota ◽  
Bony Canal ◽  
Ganglion Neurons ◽  
Temporal Bones

Objective To perform an otopathologic analysis of temporal bones (TBs) with CHARGE syndrome. Study Design Otopathologic study of human TB specimens. Setting Otopathology laboratories. Methods From the otopathology laboratories at the University of Minnesota and Massachusetts Eye and Ear Infirmary, we selected TBs from donors with CHARGE syndrome. These TBs were serially sectioned at a thickness of 20 µm, and every 10th section was stained with hematoxylin and eosin. We performed otopathologic analyses of the external ear, middle ear (middle ear cleft, mucosal lining, ossicles, mastoid, and facial nerve), and inner ear (cochlea, vestibule, internal auditory canal, and cochlear and vestibular nerves). The gathered data were statistically analyzed. Results Our study included 12 TBs from 6 donors. We found a high prevalence of abnormalities affecting the ears. The most frequent findings were stapes malformation (100%), aberrant course of the facial nerve (100%) with narrow facial recess (50%), sclerotic and hypodeveloped mastoids (50%), cochlear (100%) and vestibular (83.3%) hypoplasia with aplasia of the semicircular canals, hypoplasia and aplasia of the cochlear (66.6%) and vestibular (91.6%) nerves, and narrowing of the bony canal of the cochlear nerve (66.6%). The number of spiral ganglion and Scarpa’s ganglion neurons were decreased in all specimens (versus normative data). Conclusions In our study, CHARGE syndrome was associated with multiple TB abnormalities that may severely affect audiovestibular function and rehabilitation.

scholarly journals Monitoring of the auditory pathway maturation after early intervention during the first year of life in infants with sensorineural hearing loss

2020 ◽  
Author(s):  
F. Matin ◽  
S. Haumann ◽  
W. Roßberg ◽  
D. Mitovska ◽  
T. Lenarz ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Early Intervention ◽  
Hearing Aids ◽  
Hearing Threshold ◽  
Auditory Pathway ◽  
Auditory Brainstem Responses ◽  
First Year ◽  
Early Therapy ◽  
Hearing Thresholds ◽  
First Year Of Life

Abstract Purpose The objective of this study was to investigate the auditory pathway maturation monitored by auditory brainstem responses (ABR) in infants with hearing loss during the first year of life. ABR were used to estimate hearing thresholds and the effect of early intervention strategies using hearing aids (HA). Methods Click-evoked ABRs were measured in 102 infants aged from 0 to 12 months to determine their individual auditory threshold. Early therapy intervention was recommended before 12 months of age and analyzed. To evaluate the effect of hearing amplification on auditory maturation, different subgroups of infants with moderate hearing loss were analyzed and the auditory pathway maturation was determined based on IPL I–V shortening. Results Overall, 110 ears (54.0% of 204 ears) with mild to profound HL showed threshold changes of 10 dB up to 60 dB in the follow-up ABR testing. HA were prescribed at the age of 3.8 ± 3.9 months. Cochlear implantation (CI) was performed in cases of repeated profound HL at the age of 9.9 months ± 4.5 months. A significant shortening of IPL I–V in all subgroups of infants (with and without risk factors) who received HA was shown and assumed auditory pathway maturation. Conclusion An early intervention using optimally fitted HA influenced auditory pathway maturation and may lead to improvements of hearing thresholds during the first year of life in infants. This study underscores the importance of not only providing HAs to infants, but also controlling for hearing threshold changes ensuring that HAs provide the optimal level of intervention or CI is indicated.

Use of hearing AIDS

1976 ◽  
Vol 14 (12) ◽  
pp. 45-46
Keyword(s):  
Hearing Loss ◽  
Middle Ear ◽  
Hearing Aids ◽  
Conductive Hearing Loss ◽  
Auditory Training ◽  
Lip Reading ◽  
Conductive Hearing

Up to 3 million people in Britain might be helped by hearing aids.1 2 Most are over 65 years of age, but some are infants. All should be referred to specialist centres for assessment as soon as possible. Hearing aids generally help most in disorders of the middle ear (conductive hearing loss); they can also help those with sensorineural and other forms of hearing loss. The use of an aid often needs to be supplemented by lip reading and other means of auditory training.1 3

scholarly journals Comparison of Methods for the Histological Evaluation of Odontocete Spiral Ganglion Cells

Animals ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 683 ◽  
Author(s):  
Tania Ramírez ◽  
Simona Sacchini ◽  
Yania Paz ◽  
Rubén S. Rosales ◽  
Nakita Câmara ◽  
...  
Keyword(s):  
Cell Morphology ◽  
Ganglion Cells ◽  
Spiral Ganglion ◽  
Auditory Pathway ◽  
Histological Evaluation ◽  
Anatomical Location ◽  
Tissue Samples ◽  
Edta Solution ◽  
Ganglion Neurons ◽  
Hearing System

Cetaceans greatly depend on their hearing system to perform many vital activities. The spiral ganglion is an essential component of the auditory pathway and can even be associated with injuries caused by anthropogenic noise. However, its anatomical location, characterized by surrounding bony structures, makes the anatomical and anatomopathological study of the spiral ganglion a difficult task. In order to obtain high-quality tissue samples, a perfect balance between decalcification and the preservation of neural components must be achieved. In this study, different methodologies for spiral ganglion sample preparation and preservation were evaluated. Hydrochloric acid had the shortest decalcification time but damaged the tissue extensively. Both formic acid and EDTA decalcification solutions had a longer decalcification time but exhibited better preservation of the neurons. However, improved cell morphology and staining were observed on ears pretreated with EDTA solution. Therefore, we suggest that decalcifying methodologies based on EDTA solutions should be used to obtain the highest quality samples for studying cell morphology and antigenicity in cetacean spiral ganglion neurons.

scholarly journals Intrinsically Self-renewing Neuroprogenitors From the A/J Mouse Spiral Ganglion as Virtually Unlimited Source of Mature Auditory Neurons

2020 ◽  
Vol 14 ◽  
Author(s):  
Francis Rousset ◽  
Vivianne B. C. Kokje ◽  
Rebecca Sipione ◽  
Dominik Schmidbauer ◽  
German Nacher-Soler ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Progenitor Cells ◽  
Ganglion Cells ◽  
Spiral Ganglion ◽  
Specific Cell ◽  
Auditory Neurons ◽  
Self Renewal ◽  
Starting Point ◽  
Ganglion Neurons

Nearly 460 million individuals are affected by sensorineural hearing loss (SNHL), one of the most common human sensory disorders. In mammals, hearing loss is permanent due to the lack of efficient regenerative capacity of the sensory epithelia and spiral ganglion neurons (SGN). Sphere-forming progenitor cells can be isolated from the mammalian inner ear and give rise to inner ear specific cell types in vitro. However, the self-renewing capacities of auditory progenitor cells from the sensory and neuronal compartment are limited to few passages, even after adding powerful growth factor cocktails. Here, we provide phenotypical and functional characterization of a new pool of auditory progenitors as sustainable source for sphere-derived auditory neurons. The so-called phoenix auditory neuroprogenitors, isolated from the A/J mouse spiral ganglion, exhibit robust intrinsic self-renewal properties beyond 40 passages. At any passage or freezing–thawing cycle, phoenix spheres can be efficiently differentiated into mature spiral ganglion cells by withdrawing growth factors. The differentiated cells express both neuronal and glial cell phenotypic markers and exhibit similar functional properties as mouse spiral ganglion primary explants and human sphere-derived spiral ganglion cells. In contrast to other rodent models aiming at sustained production of auditory neurons, no genetic transformation of the progenitors is needed. Phoenix spheres therefore represent an interesting starting point to further investigate self-renewal in the mammalian inner ear, which is still far from any clinical application. In the meantime, phoenix spheres already offer an unlimited source of mammalian auditory neurons for high-throughput screens while substantially reducing the numbers of animals needed.

scholarly journals Hearing Aid Treatment for Patients with Mixed Hearing Loss. Part II: Speech Recognition in Comparison to Direct Acoustic Cochlear Stimulation

2020 ◽  
Vol 25 (3) ◽  
pp. 133-142
Author(s):  
Nina Wardenga ◽  
Ad F.M. Snik ◽  
Eugen Kludt ◽  
Bernd Waldmann ◽  
Thomas Lenarz ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Speech Recognition ◽  
Middle Ear ◽  
Hearing Aids ◽  
Dynamic Range ◽  
Hearing Aid ◽  
Middle Ear Surgery ◽  
Promising Alternative ◽  
Mixed Hearing Loss ◽  
Technical Specifications

Background: The conventional therapy for severe mixed hearing loss is middle ear surgery combined with a power hearing aid. However, a substantial group of patients with severe mixed hearing loss cannot be treated adequately with today’s state-of-the-art (SOTA) power hearing aids, as predicted by the accompanying part I of this publication, where we compared the available maximum power output (MPO) and gain from technical specifications to requirements for optimum benefit using a common fitting rule. Here, we intended to validate the theoretical assumptions from part I experimentally in a mixed hearing loss cohort fitted with SOTA power hearing aids. Additionally, we compared the results with an implantable hearing device that circumvents the impaired middle ear, directly stimulating the cochlea, as this might be a better option. Objectives: Speech recognition outcomes obtained from patients with severe mixed hearing loss supplied acutely with a SOTA hearing aid were studied to validate the outcome predictions as described in part I. Further, the results obtained with hearing aids were compared to those in direct acoustic cochlear implant (DACI) users. Materials and Methods: Twenty patients (37 ears with mixed hearing loss) were provided and fitted with a SOTA power hearing aid. Before and after an acclimatization period of at least 4 weeks, word recognition scores (WRS) in quiet and in noise were studied, as well as the speech reception threshold in noise (SRT). The outcomes were compared retrospectively to a second group of 45 patients (47 ears) using the DACI device. Based on the severity of the mixed hearing loss and the available gain and MPO of the SOTA hearing aid, the hearing aid and DACI users were subdivided into groups with prediction of sufficient, partially insufficient, or very insufficient hearing aid performance. Results: The patients with predicted adequate SOTA hearing aid performance indeed showed the best WRS in quiet and in noise when compared to patients with predicted inferior outcomes. Insufficient hearing aid performance at one or more frequencies led to a gradual decrease in hearing aid benefit, validating the criteria used here and in the accompanying paper. All DACI patients showed outcomes at the same level as the adequate hearing aid performance group, being significantly better than those of the groups with inadequate hearing aid performance. Whereas WRS in quiet and noise were sensitive to insufficient gain or output, showing significant differences between the SOTA hearing aid and DACI groups, the SRT in noise was less sensitive. Conclusions: Limitations of outcomes in mixed hearing loss individuals due to insufficient hearing aid performance can be accurately predicted by applying a commonly used fitting rule and the 35-dB dynamic range rule on the hearing aid specifications. Evidently, when outcomes in patients with mixed hearing loss using the most powerful hearing aids are insufficient, bypassing the middle ear with a powerful active middle ear implant or direct acoustic implant can be a promising alternative treatment.

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