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Lancet (London, England) May 2024Autosomal recessive deafness 9, caused by mutations of the OTOF gene, is characterised by congenital or prelingual, severe-to-complete, bilateral hearing loss. However,... (Clinical Trial)
Clinical Trial
BACKGROUND
Autosomal recessive deafness 9, caused by mutations of the OTOF gene, is characterised by congenital or prelingual, severe-to-complete, bilateral hearing loss. However, no pharmacological treatment is currently available for congenital deafness. In this Article, we report the safety and efficacy of gene therapy with an adeno-associated virus (AAV) serotype 1 carrying a human OTOF transgene (AAV1-hOTOF) as a treatment for children with autosomal recessive deafness 9.
METHODS
This single-arm, single-centre trial enrolled children (aged 1-18 years) with severe-to-complete hearing loss and confirmed mutations in both alleles of OTOF, and without bilateral cochlear implants. A single injection of AAV1-hOTOF was administered into the cochlea through the round window. The primary endpoint was dose-limiting toxicity at 6 weeks after injection. Auditory function and speech were assessed by appropriate auditory perception evaluation tools. All analyses were done according to the intention-to-treat principle. This trial is registered with Chinese Clinical Trial Registry, ChiCTR2200063181, and is ongoing.
FINDINGS
Between Oct 19, 2022, and June 9, 2023, we screened 425 participants for eligibility and enrolled six children for AAV1-hOTOF gene therapy (one received a dose of 9 × 10 vector genomes [vg] and five received 1·5 × 10 vg). All participants completed follow-up visits up to week 26. No dose-limiting toxicity or serious adverse events occurred. In total, 48 adverse events were observed; 46 (96%) were grade 1-2 and two (4%) were grade 3 (decreased neutrophil count in one participant). Five children had hearing recovery, shown by a 40-57 dB reduction in the average auditory brainstem response (ABR) thresholds at 0·5-4·0 kHz. In the participant who received the 9 × 10 vg dose, the average ABR threshold was improved from greater than 95 dB at baseline to 68 dB at 4 weeks, 53 dB at 13 weeks, and 45 dB at 26 weeks. In those who received 1·5 × 10 AAV1-hOTOF, the average ABR thresholds changed from greater than 95 dB at baseline to 48 dB, 38 dB, 40 dB, and 55 dB in four children with hearing recovery at 26 weeks. Speech perception was improved in participants who had hearing recovery.
INTERPRETATION
AAV1-hOTOF gene therapy is safe and efficacious as a novel treatment for children with autosomal recessive deafness 9.
FUNDING
National Natural Science Foundation of China, National Key R&D Program of China, Science and Technology Commission of Shanghai Municipality, and Shanghai Refreshgene Therapeutics.
Topics: Humans; Genetic Therapy; Dependovirus; Child; Male; Child, Preschool; Female; Adolescent; Infant; Genetic Vectors; Treatment Outcome; Deafness; Mutation; Membrane Proteins
PubMed: 38280389
DOI: 10.1016/S0140-6736(23)02874-X -
Otolaryngologic Clinics of North America Dec 2022The purpose of this article is to outline the current state of evaluating children with unilateral hearing loss, with significant focus on cochlear implantation, in... (Review)
Review
The purpose of this article is to outline the current state of evaluating children with unilateral hearing loss, with significant focus on cochlear implantation, in terms of reviewing the key points of the history, including the duration of deafness, outlining the recommended audiometric testing battery, and discussing issues related to imaging of the auditory system and related anatomy. In addition, a comprehensive and up-to-date summary of outcomes in terms of speech perception, sound localization, and quality of life for both the child with unilateral hearing loss as well as their parent(s) is reported.
Topics: Child; Humans; Hearing Loss, Unilateral; Quality of Life; Treatment Outcome; Cochlear Implantation; Speech Perception; Deafness; Cochlear Implants
PubMed: 36371131
DOI: 10.1016/j.otc.2022.07.003 -
Journal of the Association For Research... Feb 2023The cochlear implant (CI) is widely considered to be one of the most innovative and successful neuroprosthetic treatments developed to date. Although outcomes vary, CIs... (Review)
Review
The cochlear implant (CI) is widely considered to be one of the most innovative and successful neuroprosthetic treatments developed to date. Although outcomes vary, CIs are able to effectively improve hearing in nearly all recipients and can substantially improve speech understanding and quality of life for patients with significant hearing loss. A wealth of research has focused on underlying factors that contribute to success with a CI, and recent evidence suggests that the overall health of the cochlea could potentially play a larger role than previously recognized. This article defines and reviews attributes of cochlear health and describes procedures to evaluate cochlear health in humans and animal models in order to examine the effects of cochlear health on performance with a CI. Lastly, we describe how future biologic approaches can be used to preserve and/or enhance cochlear health in order to maximize performance for individual CI recipients.
Topics: Animals; Humans; Cochlear Implants; Quality of Life; Cochlear Implantation; Cochlea; Deafness
PubMed: 36600147
DOI: 10.1007/s10162-022-00882-y -
European Journal of Human Genetics :... Jan 2022
Topics: Deafness; Humans; Pedigree
PubMed: 34819629
DOI: 10.1038/s41431-021-01006-5 -
Ugeskrift For Laeger Dec 2023The introduction of cochlear implants (CI) for pediatric populations with deafness has changed life conditions for deaf children markedly. A new generation of children... (Review)
Review
The introduction of cochlear implants (CI) for pediatric populations with deafness has changed life conditions for deaf children markedly. A new generation of children with CI has emerged, and this review investigates how it has been documented that early intervention with CI and enrolment in family-centered auditory-verbal intervention allow children to close the language gap and develop age-equivalent language before entering school. At the school level, children keep up the language level. Most importantly children assess themselves to have levels of social well-being comparable to their peers with normal hearing.
Topics: Child; Humans; Cochlear Implantation; Deafness; Cochlear Implants
PubMed: 38078473
DOI: No ID Found -
JAMA Sep 2021
Topics: Deafness; Famous Persons; History, 18th Century; History, 19th Century; Music; Osteitis Deformans; Otosclerosis; Syphilis
PubMed: 34546309
DOI: 10.1001/jama.2020.18134 -
HNO Aug 2021This article presents a case of sudden bilateral deafness in the context of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and resultant...
This article presents a case of sudden bilateral deafness in the context of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and resultant coronavirus disease 2019 (COVID-19). After treatment in the intensive care unit for acute respiratory distress syndrome and acute kidney failure, hearing ability had drastically changed. While hearing had been subjectively normal before the infection, deafness was now measured on the left and profound hearing loss on the right ear. The patient was treated with cochlea implants on the left and a hearing aid in the right ear. The hearing loss is most likely a complication of COVID-19.
Topics: COVID-19; Cochlear Implantation; Cochlear Implants; Deafness; Hearing Loss, Sudden; Humans; RNA, Viral; SARS-CoV-2; Speech Perception
PubMed: 34019138
DOI: 10.1007/s00106-021-01041-0 -
Sante Publique (Vandoeuvre-les-Nancy,... 2022Launched in 2014, the national screening program for permanent neonatal deafness has reconfigured the care of Deaf children. By bringing forward the age of the start of...
BACKGROUND
Launched in 2014, the national screening program for permanent neonatal deafness has reconfigured the care of Deaf children. By bringing forward the age of the start of care, it promotes language development and allows these children to be referred to dedicated services more quickly.
OBJECTIVE
In this context of epidemiological reorganization and technological change (cochlear implantation in particular), the Family Support and Early Education Services of the Loire (Safep 42) propose a reflection of the type “evaluation of professional practices” around the mediations proposed in its service and the “educational garden” framework.
METHOD
This mixed-method work combines composite data: activity reports, observations, interviews, experience capture, evaluation of professional practices.
RESULTS
A decrease in the age of entry (linked to early detection) and an increase in the age of exit (due to the prevalence of children with associated disorders or complexity factors) led Safep 42 to adapt by creating new mediation, while maintaining the support provided for older children, particularly the educational garden. Safep is currently reaching its maximum capacity: in addition to this tension, there is a shortage of outpatient speech therapists and an increase in the number of deafness situations associated with multiple disabilities. The service has had to give up some of its tasks in order to be able to continue to provide proper care for the children in its care.
DISCUSSION
The rehabilitation and family support program is accompanied by a longer period of care for the children and this data must be recorded by the funding authorities.
Topics: Adolescent; Child; Cochlear Implantation; Deafness; Hearing Loss; Humans; Infant, Newborn
PubMed: 36216633
DOI: No ID Found -
Revue Neurologique Nov 2021Permanently changed sensory stimulation can modify functional connectivity patterns in the healthy brain and in pathology. In the pathology case, these adaptive... (Review)
Review
Permanently changed sensory stimulation can modify functional connectivity patterns in the healthy brain and in pathology. In the pathology case, these adaptive modifications of the brain are referred to as compensation, and the subsequent configurations of functional connectivity are called compensatory plasticity. The variability and extent of auditory deficits due to the impairments in the hearing system determine the related brain reorganization and rehabilitation. In this review, we consider cross-modal and intra-modal brain plasticity related to bilateral and unilateral hearing loss and their restoration using cochlear implantation. Cross-modal brain plasticity may have both beneficial and detrimental effects on hearing disorders. It has a beneficial effect when it serves to improve a patient's adaptation to the visuo-auditory environment. However, the occupation of the auditory cortex by visual functions may be a negative factor for the restoration of hearing with cochlear implants. In what concerns intra-modal plasticity, the loss of interhemispheric asymmetry in asymmetric hearing loss is deleterious for the auditory spatial localization. Research on brain plasticity in hearing disorders can advance our understanding of brain plasticity and improve the rehabilitation of the patients using prognostic, evidence-based approaches from cognitive neuroscience combined with post-rehabilitation objective biomarkers of this plasticity utilizing neuroimaging.
Topics: Auditory Cortex; Cochlear Implantation; Cochlear Implants; Deafness; Humans; Neuronal Plasticity
PubMed: 34657730
DOI: 10.1016/j.neurol.2021.09.004 -
Frontiers in Endocrinology 2021To investigate the clinical features and mitochondrial mutations for maternally inherited diabetes and deafness. (Review)
Review
AIMS
To investigate the clinical features and mitochondrial mutations for maternally inherited diabetes and deafness.
METHODS
PubMed, Embase, Medline, Web of Science, the China National Knowledge Infrastructure, and Wanfang were searched with the following search terms: "Maternally inherited diabetes and deafness" OR "MIDD" OR "Mitochondrial diabetes". The mutations and clinical features were analyzed. Correlation between the heteroplasmy levels of the m.3243A>G mutation in the peripheral blood and age at the onset of diabetes was conducted by Spearman test. The significance level was set as p < 0.05. Statistical analysis was performed using the Statistical Package for the Social Sciences version 26 for Windows.
RESULTS
Totally 161 patients with 21 different mitochondrial mutations were enrolled. The most common mutation was the m.3243A>G mutation in 136 cases. Of 142 patients, 120 (84.51%) had family histories of diabetes or hearing loss. Hearing loss presented in 85.71% of the patients with mitochondrial mutations. Central nervous system diseases were found in 29.19%, myopathy in 22.98%, oculopathy in 23.60%, cardiac disease in 23.60%, and nephropathy in 13.66% of the patients. Forty-two of 101 (41.58%) patients were underweight. A significant negative correlation was found between the heteroplasmy levels of the m.3243A>G mutation in the peripheral blood and age at the onset of diabetes.
CONCLUSIONS
The young onset of diabetes with low or normal BMI, maternal inheritance, and presence of impairments of multiple systems should prompt a genetic testing in order to differentiate MIDD from other types of diabetes earlier.
Topics: Biological Variation, Population; Cohort Studies; DNA, Mitochondrial; Deafness; Diabetes Mellitus, Type 2; Genetic Heterogeneity; Humans; Infant, Newborn; Mitochondrial Diseases; Mutation; Phenotype
PubMed: 34899594
DOI: 10.3389/fendo.2021.728043