Rescue of Hearing by Gene Delivery to Inner-Ear Hair Cells Using Exosome-Associated AAV.

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Rescue of Hearing by Gene Delivery to Inner-Ear Hair Cells Using Exosome-Associated AAV.

Mol Ther. 2017 Jan 09;:

Authors: György B, Sage C, Indzhykulian AA, Scheffer DI, Brisson AR, Tan S, Wu X, Volak A, Mu D, Tamvakologos PI, Li Y, Fitzpatrick Z, Ericsson M, Breakefield XO, Corey DP, Maguire CA

Abstract
Adeno-associated virus (AAV) is a safe and effective vector for gene therapy for retinal disorders. Gene therapy for hearing disorders is not as advanced, in part because gene delivery to sensory hair cells of the inner ear is inefficient. Although AAV transduces the inner hair cells of the mouse cochlea, outer hair cells remain refractory to transduction. Here, we demonstrate that a vector, exosome-associated AAV (exo-AAV), is a potent carrier of transgenes to all inner ear hair cells. Exo-AAV1-GFP is more efficient than conventional AAV1-GFP, both in mouse cochlear explants in vitro and with direct cochlear injection in vivo. Exo-AAV shows no toxicity in vivo, as assayed by tests of auditory and vestibular function. Finally, exo-AAV1 gene therapy partially rescues hearing in a mouse model of hereditary deafness (lipoma HMGIC fusion partner-like 5/tetraspan membrane protein of hair cell stereocilia [Lhfpl5/Tmhs(-/-)]). Exo-AAV is a powerful gene delivery system for hair cell research and may be useful for gene therapy for deafness.

PMID: 28082074 [PubMed - as supplied by publisher]

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Rescue of Hearing by Gene Delivery to Inner-Ear Hair Cells Using Exosome-Associated AAV.

Related Articles

Rescue of Hearing by Gene Delivery to Inner-Ear Hair Cells Using Exosome-Associated AAV.

Mol Ther. 2017 Jan 09;:

Authors: György B, Sage C, Indzhykulian AA, Scheffer DI, Brisson AR, Tan S, Wu X, Volak A, Mu D, Tamvakologos PI, Li Y, Fitzpatrick Z, Ericsson M, Breakefield XO, Corey DP, Maguire CA

Abstract
Adeno-associated virus (AAV) is a safe and effective vector for gene therapy for retinal disorders. Gene therapy for hearing disorders is not as advanced, in part because gene delivery to sensory hair cells of the inner ear is inefficient. Although AAV transduces the inner hair cells of the mouse cochlea, outer hair cells remain refractory to transduction. Here, we demonstrate that a vector, exosome-associated AAV (exo-AAV), is a potent carrier of transgenes to all inner ear hair cells. Exo-AAV1-GFP is more efficient than conventional AAV1-GFP, both in mouse cochlear explants in vitro and with direct cochlear injection in vivo. Exo-AAV shows no toxicity in vivo, as assayed by tests of auditory and vestibular function. Finally, exo-AAV1 gene therapy partially rescues hearing in a mouse model of hereditary deafness (lipoma HMGIC fusion partner-like 5/tetraspan membrane protein of hair cell stereocilia [Lhfpl5/Tmhs(-/-)]). Exo-AAV is a powerful gene delivery system for hair cell research and may be useful for gene therapy for deafness.

PMID: 28082074 [PubMed - as supplied by publisher]

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Making sound waves: selected papers from the 2016 annual conference of the National Hearing Conservation Association.

Making sound waves: selected papers from the 2016 annual conference of the National Hearing Conservation Association.

Int J Audiol. 2017 Jan 13;:S1-S3

Authors: Murphy WJ, Le Prell CG

PMID: 28084117 [PubMed - as supplied by publisher]

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Book Review.

Book Review.

Int J Audiol. 2017 Jan 13;:1-2

Authors: Stacey L

PMID: 28084104 [PubMed - as supplied by publisher]

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The IJA system for systematic reviews: "the whys and hows"().

The IJA system for systematic reviews: "the whys and hows"().

Int J Audiol. 2017 Jan 13;:1-3

Authors: Morata TC, Hickson L, Wong L

PMID: 28084088 [PubMed - as supplied by publisher]

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The Sound Access Parent Outcomes Instrument (SAPOI): Construction of a new instrument for children with severe multiple disabilities who use cochlear implants or hearing aids.

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The Sound Access Parent Outcomes Instrument (SAPOI): Construction of a new instrument for children with severe multiple disabilities who use cochlear implants or hearing aids.

Cochlear Implants Int. 2016;17(2):81-9

Authors: Hayward DV, Ritter K, Mousavi A, Vatanapour S

Abstract
OBJECTIVE: To report on the Phase 2 development of the Sound Access Parent Outcomes Instrument (SAPOI), a new instrument focused on formalizing outcomes that parents of children with severe multiple disabilities (SMD) who use amplification prioritize as important.
METHODS: Phase 2 of this project involved item selection and refinement of the SAPOI based on (a) Phase 1 study participant input, (b) clinical specialist feedback, and (c) test-retest instrument reliability. Phase 1 participant responses were utilized to construct a draft version of the SAPOI. Next, clinical specialists examined the instrument for content validity and utility and instrument reliability was examined through a test-retest process with parents of children with SMD.
RESULTS: The draft SAPOI was constructed based on Phase 1 participant input. Clinical specialists supported content validity and utility of the instrument and the inclusion of 19 additional items across four categories, namely Child Affect, Child Interaction, Parent Well-being, and Child's Device Use. The SAPOI was completed twice at one-month intervals by parents of children with SMD to examine instrument reliability across the four categories (Child Affect, Child Interaction, Parent Well-being, and Child's Device Use). Instrument reliability was strong-to-excellent across all four sections.
DISCUSSION: The SAPOI shows promise as a much-needed addition to the assessment battery currently used for children with SMD who use cochlear implants and hearing aids. It provides valuable information regarding outcomes resulting from access to sound in this population that currently used assessments do not identify.

PMID: 26841928 [PubMed - indexed for MEDLINE]

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Assessment of the psychosocial impacts of cochlear implants on adult recipients and their partners.

Related Articles

Assessment of the psychosocial impacts of cochlear implants on adult recipients and their partners.

Cochlear Implants Int. 2016;17(2):90-7

Authors: Chen S, Karamy B, Shipp D, Nedzelski J, Chen J, Lin V

Abstract
OBJECTIVES: In the present study we sought to evaluate the psychosocial and quality of life (QOL) impacts of cochlear implant (CI) treatment on both CI recipients and their partners in a Canadian population.
METHODS: A qualitative cross-sectional contemporary cohort evaluation was conducted by distributing specifically designed questionnaires to both CI recipients and their partners at their follow-up appointments over a month at Sunnybrook Health Sciences Centre.
RESULTS: It was found that both CI recipients and their partners demonstrated substantial benefit and improvement in multiple psychosocial domains.
DISCUSSION: Musical listening was found to show variable improvements between recipients. Further analysis found a simple correlation where the group of recipients who all had a hearing disability for a longer duration had demonstrated a higher proportion of improvement in musical listening. CI recipients endorsed having improved QOL which was in agreement with proxy observation by partners.
CONCLUSION: Overall, CI use has been shown to have significant benefit to psychosocial well-being of CI recipients. This benefit is also conferred to their caregivers/partners; which in our society concerned about caregiver burden is quite important to recognize.

PMID: 26839952 [PubMed - indexed for MEDLINE]

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Making sound waves: selected papers from the 2016 annual conference of the National Hearing Conservation Association.

Making sound waves: selected papers from the 2016 annual conference of the National Hearing Conservation Association.

Int J Audiol. 2017 Jan 13;:S1-S3

Authors: Murphy WJ, Le Prell CG

PMID: 28084117 [PubMed - as supplied by publisher]

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Book Review.

Book Review.

Int J Audiol. 2017 Jan 13;:1-2

Authors: Stacey L

PMID: 28084104 [PubMed - as supplied by publisher]

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The IJA system for systematic reviews: "the whys and hows"().

The IJA system for systematic reviews: "the whys and hows"().

Int J Audiol. 2017 Jan 13;:1-3

Authors: Morata TC, Hickson L, Wong L

PMID: 28084088 [PubMed - as supplied by publisher]

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Making sound waves: selected papers from the 2016 annual conference of the National Hearing Conservation Association.

Making sound waves: selected papers from the 2016 annual conference of the National Hearing Conservation Association.

Int J Audiol. 2017 Jan 13;:S1-S3

Authors: Murphy WJ, Le Prell CG

PMID: 28084117 [PubMed - as supplied by publisher]

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via IFTTT

Book Review.

Book Review.

Int J Audiol. 2017 Jan 13;:1-2

Authors: Stacey L

PMID: 28084104 [PubMed - as supplied by publisher]

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via IFTTT

The IJA system for systematic reviews: "the whys and hows"().

The IJA system for systematic reviews: "the whys and hows"().

Int J Audiol. 2017 Jan 13;:1-3

Authors: Morata TC, Hickson L, Wong L

PMID: 28084088 [PubMed - as supplied by publisher]

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Making sound waves: selected papers from the 2016 annual conference of the National Hearing Conservation Association.

Making sound waves: selected papers from the 2016 annual conference of the National Hearing Conservation Association.

Int J Audiol. 2017 Jan 13;:S1-S3

Authors: Murphy WJ, Le Prell CG

PMID: 28084117 [PubMed - as supplied by publisher]

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via IFTTT

Book Review.

Book Review.

Int J Audiol. 2017 Jan 13;:1-2

Authors: Stacey L

PMID: 28084104 [PubMed - as supplied by publisher]

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via IFTTT

The IJA system for systematic reviews: "the whys and hows"().

The IJA system for systematic reviews: "the whys and hows"().

Int J Audiol. 2017 Jan 13;:1-3

Authors: Morata TC, Hickson L, Wong L

PMID: 28084088 [PubMed - as supplied by publisher]

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