scholarly journals Cochlear Gene Therapy for Sensorineural Hearing Loss: Current Status and Major Remaining Hurdles for Translational Success

Author(s):  
Wenjuan Zhang ◽  
Sun Myoung Kim ◽  
Wenwen Wang ◽  
Cuiyuan Cai ◽  
Yong Feng ◽  
...  
2021 ◽  
Vol 21 ◽  
pp. 209-236
Author(s):  
Kamakshi Bankoti ◽  
Charles Generotti ◽  
Tiffany Hwa ◽  
Lili Wang ◽  
Bert W. O’Malley ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Chang-qiang Tan ◽  
Xia Gao ◽  
Wen-jun Cai ◽  
Xiao-yun Qian ◽  
Ling Lu ◽  
...  

This study aimed to investigate the efficacy of gene therapy for treating autoimmune sensorineural hearing loss (ASHL) via local administration of a recombinant adenovirus vector containing the Fas ligand or interleukin IL-10 gene. Guinea pigs were divided into four groups, with different microinjections in the scala tympani. Group A were injected with FasL-EGFP, B with IL-10-EGFP, C with EGFP, and D with artificial perilymph. Seven days later, auditory brain-stem response (ABR) was tested, and the temporal bone was stained and observed by light microscopy. The spiral ligament and basement membrane were observed using transmission electron microscopy. FasL and IL-10 expression were examined using immunofluorescence histochemistry. Immunohistochemical analysis showed that the recombinant adenovirus vector in Groups A, B, and C can transfect the stria vascularis, the spiral ligament, the organ of Corti, the spiral ganglion, the region surrounding the small blood vessel in the modiolus, and the cochlear bone wall. Compared with those in Groups C and D, the ABR wave III mean thresholds were significantly lower and the inner ear immunoinflammatory responses in Groups A and B were significantly alleviated. Inhibition of immunoinflammatory response alleviated immunoinflammatory injury and auditory dysfunction. This technique shows potential as a novel therapy for ASHL.


2015 ◽  
Vol 36 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Wade W. Chien ◽  
Elyssa L. Monzack ◽  
Devin S. McDougald ◽  
Lisa L. Cunningham

Gene Therapy ◽  
2004 ◽  
Vol 11 (S1) ◽  
pp. S51-S56 ◽  
Author(s):  
M Duan ◽  
F Venail ◽  
N Spencer ◽  
M Mezzina

2021 ◽  
Vol 15 ◽  
Author(s):  
Dorien Verdoodt ◽  
Noa Peeleman ◽  
Guy Van Camp ◽  
Vincent Van Rompaey ◽  
Peter Ponsaerts

Background: Hearing impairment is the most frequent sensory deficit, affecting 466 million people worldwide and has been listed by the World Health Organization (WHO) as one of the priority diseases for research into therapeutic interventions to address public health needs. Inner ear gene therapy is a promising approach to restore sensorineural hearing loss, for which several gene therapy applications have been studied and reported in preclinical animal studies.Objective: To perform a systematic review on preclinical studies reporting cochlear gene therapy, with a specific focus on transduction efficiency.Methods: An initial PubMed search was performed on April 1st 2021 using the PRISMA methodology. Preclinical in vivo studies reporting primary data regarding transduction efficiency of gene therapy targeting the inner ear were included in this report.Results: Thirty-six studies were included in this review. Transduction of various cell types in the inner ear can be achieved, according to the viral vector used. However, there is significant variability in the applied vector delivery systems, including promoter, viral vector titer, etc.Conclusion: Although gene therapy presents a promising approach to treat sensorineural hearing loss in preclinical studies, the heterogeneity of methodologies impedes the identification of the most promising tools for future use in inner ear therapies.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Min Yong Lee ◽  
Yong-Ho Park

Sensorineural hearing loss is caused by the loss of sensory hair cells (HCs) or a damaged afferent nerve pathway to the auditory cortex. The most common option for the treatment of sensorineural hearing loss is hearing rehabilitation using hearing devices. Various kinds of hearing devices are available but, despite recent advancements, their perceived sound quality does not mimic that of the “naïve” cochlea. Damage to crucial cochlear structures is mostly irreversible and results in permanent hearing loss. Cochlear HC regeneration has long been an important goal in the field of hearing research. However, it remains challenging because, thus far, no medical treatment has successfully regenerated cochlear HCs. Recent advances in genetic modulation and developmental techniques have led to novel approaches to generating HCs or protecting against HC loss, to preserve hearing. In this review, we present and review the current status of two different approaches to restoring or protecting hearing, gene therapy, including the newly introduced CRISPR/Cas9 genome editing, and stem cell therapy, and suggest the future direction.


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