Methionine Sulfoxide Reductase B3-Targeted In Utero Gene Therapy Rescues Hearing Function in a Mouse Model of Congenital Sensorineural Hearing Loss

BACKGROUND: Celiac disease (CD) can be associated with a variety of extraintestinal manifestations, including neurological diseases. A new neurological correlation has been found between CD and sensorineural hearing loss (SNHL).OBJECTIVE: To verify the association between SNHL and CD, and to establish whether the neurological hearing impairment in CD is related to nonorgan-specific and antineuronal antibodies, as well as the presence of autoimmune disorders.METHODS: A sample of 59 consecutive biopsy- and serologically proven CD patients were studied. Among CD patients, 11 were newly diagnosed and 48 were on a gluten-free diet. Hearing function was assessed by audiometric analysis in all CD patients as well as in 59 age- and sex-matched controls. Patients were tested for a panel of immune markers including nonorgan-specific autoantibodies and antineuronal antibodies.RESULTS: SNHL was detected in five CD patients (8.5%) and in two controls (3.4%). In one patient, the SNHL was bilateral, whereas the remaining four had a monolateral impairment. The prevalence of SNHL was not significantly different between CD patients and controls. At least one of the antibodies tested for was positive in two of the five CD patients with SNHL and in 12 of the 54 CD patients without SNHL. Antineuronal antibodies to central nervous system antigens were consistently negative in the five CD patients with SNHL. Only one of the five CD patients with SNHL had Hashimoto thyroiditis.CONCLUSIONS: SNHL and CD occur coincidentally. Hearing function should be assessed only in CD patients with clinical signs of hearing deficiency.

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Establishment of a model of cochlear lesions in rats to study potential gene therapy for sensorineural hearing loss

International Journal of Pediatric Otorhinolaryngology ◽

10.1016/j.ijporl.2015.09.037 ◽

2015 ◽

Vol 79 (12) ◽

pp. 2147-2154 ◽

Cited By ~ 2

Author(s):

Ye Wang ◽

Li Qiao ◽

Yang Chen ◽

Liting Wen ◽

Bo Yue ◽

...

Keyword(s):

Gene Therapy ◽

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Sensorineural Hearing

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Experimental Study of Local Inner Ear Gene Therapy for Controlling Autoimmune Sensorineural Hearing Loss

BioMed Research International ◽

10.1155/2014/134658 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Chang-qiang Tan ◽

Xia Gao ◽

Wen-jun Cai ◽

Xiao-yun Qian ◽

Ling Lu ◽

...

Keyword(s):

Gene Therapy ◽

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Inner Ear ◽

Recombinant Adenovirus ◽

Adenovirus Vector ◽

Sensorineural Hearing ◽

Spiral Ligament ◽

Small Blood Vessel ◽

Recombinant Adenovirus Vector

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.

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