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Human Gene Therapy Sep 2023Inherited forms of blindness and deafness are highly prevalent and severe conditions that significantly impact the lives of millions of people worldwide. The lack of... (Review)
Review
Inherited forms of blindness and deafness are highly prevalent and severe conditions that significantly impact the lives of millions of people worldwide. The lack of therapeutic options for these conditions poses a major socioeconomic burden. Over the last decades, gene therapy has proven to be a life changing treatment for hereditary and acquired forms of diseases, and extensive preclinical investigation in animal models of both retinal and inner ear disorders has highlighted promising translational opportunities for these disorders too. This led to dozens of clinical trials investigating the efficiency of gene therapy-based approaches, with some of the products for retinal conditions successfully reaching phase III of development or even market authorization. However, challenges remain for the use of gene therapy, which are related to both the features of the delivery vehicles currently available and characteristics of the retinal and inner ear disorders targeted. Therefore, further developments in gene therapy platforms' design, including exploitation of novel technologies such as genome editing, RNA-targeted therapies, and optogenetics, are actively ongoing, driving the field forward. In this study, we review the ongoing applications and achievements of gene therapy for treatment of inherited forms of blindness and deafness as well as the developments that are being pursued in the field to overcome the current limitations.
Topics: Animals; Hearing Loss; Blindness; Genetic Therapy; Deaf-Blind Disorders; Deafness
PubMed: 37642267
DOI: 10.1089/hum.2023.126 -
Practical Neurology Apr 2020There are over 87 000 Deaf people in the UK with British Sign Language (BSL) as their first language.1 Few healthcare professionals receive training in Deaf awareness... (Review)
Review
There are over 87 000 Deaf people in the UK with British Sign Language (BSL) as their first language.1 Few healthcare professionals receive training in Deaf awareness or in BSL, and missed diagnoses and inadequate treatment of Deaf patients are estimated to cost the National Health Service £30 million per year.2 Neurologists are likely to encounter Deaf BSL users in their practice, but without prior experience may find consultations challenging, especially within the time constraints and pressure of a standard clinic. In this article, we provide guidance on consulting with Deaf people in a neurology clinic, drawing on experience from our cognitive clinic for Deaf BSL users where effective communication is essential.
Topics: Ambulatory Care Facilities; Deafness; Humans; Neurology; Practice Guidelines as Topic; Sign Language; State Medicine; United Kingdom
PubMed: 31757818
DOI: 10.1136/practneurol-2019-002422 -
Expert Review of Medical Devices 2023Cochlear implants (CIs) provide access to sound for children and adults who do not receive adequate benefit from hearing aids. Age at implantation is known to affect... (Review)
Review
INTRODUCTION
Cochlear implants (CIs) provide access to sound for children and adults who do not receive adequate benefit from hearing aids. Age at implantation is known to affect outcomes across the lifespan.
AREAS COVERED
The effects of age on CI outcomes are examined for infants, children, adolescents, and older adults. A variety of outcome measures are considered, including speech perception, language, cognition, and quality of life measures.
EXPERT OPINION/COMMENTARY
For those meeting candidacy criteria, CIs are beneficial at any age. In general, younger age is related to greater benefit when considering pre-lingual deafness. Other factors such as additional disabilities, may mitigate this effect. Post-lingually deafened adults demonstrate similar benefit regardless of age, though the oldest individuals (80+) may see smaller degrees of improvement from preoperative scores. Benefit can be measured in many ways, and the areas of greatest benefit may vary based on age: young children appear to see the greatest effects of age at implantation on language measures, whereas scores on cognitive measures appear to be most impacted for the oldest population. Future research should consider implantation at extreme ages (5-9 months or > 90 years), unconventional measures of CI benefit including qualitative assessments, and longitudinal designs.
Topics: Child; Infant; Adolescent; Humans; Child, Preschool; Aged; Cochlear Implants; Deafness; Quality of Life; Cochlear Implantation; Hearing Aids; Speech Perception
PubMed: 37969071
DOI: 10.1080/17434440.2023.2283619 -
American Annals of the Deaf 2022
Topics: Humans; Deafness; Adaptation, Psychological
PubMed: 36314171
DOI: 10.1353/aad.2022.0037 -
Pediatrics Jul 2015Deafness affects ∼2 in 1000 children and is one of the most common congenital impairments. Permanent hearing loss can be treated by fitting hearing aids. More severe... (Review)
Review
Deafness affects ∼2 in 1000 children and is one of the most common congenital impairments. Permanent hearing loss can be treated by fitting hearing aids. More severe to profound deafness is an indication for cochlear implantation. Although newborn hearing screening programs have increased the identification of asymmetric hearing loss, parents and caregivers of children with single-sided deafness are often hesitant to pursue therapy for the deaf ear. Delayed intervention has consequences for recovery of hearing. It has long been reported that asymmetric hearing loss/single-sided deafness compromises speech and language development and educational outcomes in children. Recent studies in animal models of deafness and in children consistently show evidence of an "aural preference syndrome" in which single-sided deafness in early childhood reorganizes the developing auditory pathways toward the hearing ear, with weaker central representation of the deaf ear. Delayed therapy consequently compromises benefit for the deaf ear, with slow rates of improvement measured over time. Therefore, asymmetric hearing needs early identification and intervention. Providing early effective stimulation in both ears through appropriate fitting of auditory prostheses, including hearing aids and cochlear implants, within a sensitive period in development has a cardinal role for securing the function of the impaired ear and for restoring binaural/spatial hearing. The impacts of asymmetric hearing loss on the developing auditory system and on spoken language development have often been underestimated. Thus, the traditional minimalist approach to clinical management aimed at 1 functional ear should be modified on the basis of current evidence.
Topics: Child; Child Development; Child, Preschool; Deafness; Hearing Aids; Hearing Tests; Humans; Language Development; Persons With Hearing Impairments
PubMed: 26055845
DOI: 10.1542/peds.2014-3520 -
Cellular and Molecular Life Sciences :... Feb 2020Estrogen is the major female hormone involved in reproductive functions, but it also exerts a variety of additional roles in non-reproductive organs. In this review, we... (Review)
Review
Estrogen is the major female hormone involved in reproductive functions, but it also exerts a variety of additional roles in non-reproductive organs. In this review, we highlight the preclinical and clinical studies that have pointed out sex differences and estrogenic influence on audition. We also describe the experimental evidences supporting a protective role of estrogen towards acquired forms of hearing loss. Although a high level of endogenous estrogen is associated with a better hearing function, hormonal treatments at menopause have provided contradictory outcomes. The various factors that are likely to explain these discrepancies include the treatment regimen as well as the hormonal status and responsiveness of the patients. The complexity of estrogen signaling is being untangled and many downstream effectors of its genomic and non-genomic actions have been identified in other systems. Based on these advances and on the common physio-pathological events that underlie age-related, drug or noise-induced hearing loss, we discuss potential mechanisms for their protective actions in the cochlea.
Topics: Animals; Cochlea; Deafness; Estrogens; Female; Hearing; Humans; Male; Receptors, Estrogen; Sex Characteristics; Sex Factors; Signal Transduction
PubMed: 31522250
DOI: 10.1007/s00018-019-03295-y -
Genetics in Medicine : Official Journal... Sep 2022Genes associated with nonsyndromic hearing loss are commonly included in reproductive carrier screening panels, which are now routinely offered in preconception and... (Review)
Review
PURPOSE
Genes associated with nonsyndromic hearing loss are commonly included in reproductive carrier screening panels, which are now routinely offered in preconception and prenatal care in many countries. However, there is debate whether hearing loss should be considered a medical condition appropriate for screening. This systematic review assessed research on opinions of those with a lived experience of deafness and the general public regarding genetic testing for deafness in the reproductive setting.
METHODS
Search of 5 online databases yielded 423 articles, 20 of which met inclusion criteria. We assessed the quality of each study, extracted data, and performed thematic analysis on qualitative studies.
RESULTS
Most studies indicated interest in the use of prenatal diagnosis for deafness. However, there were mixed views, and sometimes strongly held views, expressed regarding the reproductive options that should be available to those with an increased chance of having a child with deafness. Studies were small, from a limited number of countries, and most were too old to include views regarding preimplantation genetic testing.
CONCLUSION
There is a broad range of views regarding the use of reproductive options for deafness. Further research is essential to explore the benefits and harms of including nonsyndromic hearing loss genes in carrier screening.
Topics: Child; Deafness; Female; Genetic Testing; Humans; Pregnancy; Prenatal Diagnosis; Reproduction
PubMed: 35659827
DOI: 10.1016/j.gim.2022.05.005 -
Journal of Genetics and Genomics = Yi... Jun 2017Hearing loss is the most common sensorineural disorder worldwide and is associated with more than 1000 mutations in more than 90 genes. While mutations in genes such as... (Review)
Review
Hearing loss is the most common sensorineural disorder worldwide and is associated with more than 1000 mutations in more than 90 genes. While mutations in genes such as GJB2 (gap-junction protein β 2) and GJB6 (gap-junction protein β 6) are highly prevalent in Caucasian, Asian, and Middle Eastern populations, they are rare in both native African populations and those of African descent. The objective of this paper is to review the current knowledge regarding the epidemiology and genetics of hearing loss in African populations with a focus on native sub-Saharan African populations. Environmental etiologies related to poor access to healthcare and perinatal care account for the majority of cases. Syndromic etiologies including Waardenburg, Pendred and Usher syndromes are uncommon causes of hearing loss in these populations. Of the non-syndromic causes, common mutations in GJB2 and GJB6 are rarely implicated in populations of African descent. Recent use of next-generation sequencing (NGS) has identified several candidate deafness genes in African populations from Nigeria and South Africa that are unique when compared to common causative mutations worldwide. Researchers also recently described a dominant mutation in MYO3a in an African American family with non-syndromic hearing loss. The use of NGS and specialized panels will aid in identifying rare and novel mutations in a more cost- and time-effective manner. The identification of common hearing loss mutations in indigenous African populations will pave the way for translation into genetic deafness research in populations of African descent worldwide.
Topics: Black People; Deafness; Environment; Humans
PubMed: 28642064
DOI: 10.1016/j.jgg.2017.03.008 -
Otology & Neurotology : Official... Dec 2016Considerable unexplained variability and large individual differences exist in speech recognition outcomes for postlingually deaf adults who use cochlear implants (CIs),... (Review)
Review
OBJECTIVE
Considerable unexplained variability and large individual differences exist in speech recognition outcomes for postlingually deaf adults who use cochlear implants (CIs), and a sizeable fraction of CI users can be considered "poor performers." This article summarizes our current knowledge of poor CI performance, and provides suggestions to clinicians managing these patients.
METHOD
Studies are reviewed pertaining to speech recognition variability in adults with hearing loss. Findings are augmented by recent studies in our laboratories examining outcomes in postlingually deaf adults with CIs.
RESULTS
In addition to conventional clinical predictors of CI performance (e.g., amount of residual hearing, duration of deafness), factors pertaining to both "bottom-up" auditory sensitivity to the spectro-temporal details of speech, and "top-down" linguistic knowledge and neurocognitive functions contribute to CI outcomes.
CONCLUSIONS
The broad array of factors that contribute to speech recognition performance in adult CI users suggests the potential both for novel diagnostic assessment batteries to explain poor performance, and also new rehabilitation strategies for patients who exhibit poor outcomes. Moreover, this broad array of factors determining outcome performance suggests the need to treat individual CI patients using a personalized rehabilitation approach.
Topics: Adult; Cochlear Implantation; Cochlear Implants; Deafness; Humans; Persons With Hearing Impairments; Speech Perception
PubMed: 27631833
DOI: 10.1097/MAO.0000000000001211 -
ORL; Journal For Oto-rhino-laryngology... 2021This study aims to analyze possible preoperative factors taken from the medical history that may assist the otolaryngologist in counseling an adult patient before...
INTRODUCTION
This study aims to analyze possible preoperative factors taken from the medical history that may assist the otolaryngologist in counseling an adult patient before cochlear implantation (CI).
OBJECTIVE
Analysis of preoperative factors taken during the initial patient presentation for a possible prognostic role in the auditory rehabilitation outcome.
METHODS
A cohort of 232 (272 CI implantations) postlingually deafened adults was evaluated in this study. Hearing results at 1, 2, and up to 3 years postoperatively were compared with various preoperative factors: living status, cause of deafness, gender, side of implantation, residual hearing, and duration of deafness. Postoperative hearing performance was measured based on the German Freiburg monosyllabic word test and the Oldenburg sentence test.
RESULTS
Duration of deafness showed a negative correlation to word recognition and a positive correlation to increased speech reception threshold in sentence testing. A significant decline in hearing outcome was shown starting around the second decade of deafness. Residual hearing as defined in our cohort and side of implantation showed limited benefit in speech understanding. Living status, gender, and cause of deafness did not show any prognostic value.
CONCLUSION
In this retrospective review it could be shown that simple case history information can only provide limited prognostic insight before CI. The duration of deafness is the most reliable anamnestic factor present on initial patient evaluation.
Topics: Adult; Cochlear Implantation; Cochlear Implants; Deafness; Humans; Prognosis; Retrospective Studies; Speech Perception; Treatment Outcome
PubMed: 32950987
DOI: 10.1159/000509562