In Vitro and In Vivo Assessment of the Ability of Adeno‐Associated Virus–Brain‐Derived Neurotrophic Factor to Enhance Spiral Ganglion Cell Survival Following Ototoxic Insult

Lalwani, Anil K.; Han, Jay J.; Castelein, Caley M.; Carvalho, Gerard J.; Mhatre, Anand N.

doi:10.1097/00005537-200208000-00001

Cited by 46 publications

(39 citation statements)

References 50 publications

(66 reference statements)

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“…This pattern of protection has been previously noted in viral mediated gene therapy via round window inoculations (Lalwani et al, 2002;Yagi et al, 2000). This is likely to reflect the pattern of diffusion of released neurotrophic factors in the scala tympani.…”

Section: Discussionsupporting

confidence: 73%

“…The extent of spiral ganglion neuron protection with our BDNF electrode is comparable to previous work using viral vectors and neurotrophic factor transgenes including GDNF and BDNF (Kanzaki et al, 2002;Lalwani et al, 2002), even after differences in experimental design are taken into account. In all these experiments, spiral ganglion cell protection was significant but incomplete.…”

Section: Discussionsupporting

confidence: 73%

“…Spiral ganglion cell survival has been shown to be influenced by treatment with several growth factors. Specifically, neurotophic factors such as GDNF, NT-3 and BDNF can protect the eighth nerve from degeneration (Bowers et al, 2002;Lalwani et al, 2002;Miller et al, 1997;Staecker et al, 1998;Yagi et al, 2000;Ylikoski et al, 1998). Attempts to combine cochlear implantation with over-expression of a neurotrophic factor were performed using viral vectors to over-express GDNF (Kanzaki et al, 2002) or passive release from NT-3 from a polypyrrole polymer (Richardson et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

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Cochlear implants and ex vivo BDNF gene therapy protect spiral ganglion neurons

et al. 2007

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Spiral ganglion neurons often degenerate in the deaf ear, compromising the function of cochlear implants. Cochlear implant function can be improved by good preservation of the spiral ganglion neurons, which are the target of electrical stimulation by the implant. Brain derived neurotrophic factor (BDNF) has previously been shown to enhance spiral ganglion survival in experimentally deafened ears. Providing enhanced levels of BDNF in human ears may be accomplished by one of several different methods. The goal of these experiments was to test a modified design of the cochlear implant electrode that includes a coating of fibroblast cells transduced by a viral vector with a BDNF gene insert. To accomplish this type of ex vivo gene transfer, we transduced guinea pig fibroblasts with an adenovirus with a BDNF gene cassette insert, and determined that these cells secreted BDNF. We then attached BDNF-secreting cells to the cochlear implant electrode via an agarose gel, and implanted the electrode in the scala tympani. We determined that the BDNF expressing electrodes were able to preserve significantly more spiral ganglion neurons in the basal turns of the cochlea after 48 days of implantation when compared to control electrodes. This protective effect decreased in the higher cochlear turns. The data demonstrate the feasibility of combining cochlear implant therapy with ex vivo gene transfer for enhancing spiral ganglion neuron survival.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

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Cochlear implants and ex vivo BDNF gene therapy protect spiral ganglion neurons

et al. 2007

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“…Transfer of the BDNF [Lalwani et al, 2002;Nakaizumi et al, 2004;Staecker et al, 1998], GDNF [Hakuba et al, 2003;Kawamoto et al, 2001aKawamoto et al, , 2003bSuzuki et al, 2000;Yagi et al, 1999Yagi et al, , 2000 or NT-3 [Bowers et al, 2002] genes in the cochlea gave comparable outcomes to conventional exogenous delivery of neurotrophic factors, for example via pumps, in terms of SGN or HC survival. However, the potential to use cell-specific promoters to express a gene in specific cell types of the cochlea, whilst leaving other cells unaffected, gives gene therapy an advantage over other types of therapies.…”

Section: Slow-release Polymers and Hydrogelsmentioning

confidence: 99%

Inner Ear Therapy for Neural Preservation

2006

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A gradual loss of auditory neurons often occurs following sensorineural hearing loss. Since the cochlear implant must stimulate the remaining auditory neuron population, it would be beneficial to preserve as many auditory neurons as possible. Neurotrophic factors protect auditory neurons from degradation after sensorineural hearing loss in experimental animals, but have not yet been translated into the clinical setting. Current experimental and clinical techniques for drug delivery to the inner ear are examined in this review, covering the routes for drug delivery to the cochlea and the delivery systems used to introduce them. Duration of treatment, drug diffusion, effectiveness and safety are discussed with references to how they may be translated to the implementation of neurotrophic factor treatment for neural preservation.

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“…Transfer of BDNF, GDNF or NT-3 genes into the cochlea has resulted in SGN protection comparable to that achieved with neurotrophic factors delivered to the cochlea as a protein solution [37,[89][90][91][92]. However, gene therapy has the potential benefit of enabling cell-specific expression of genes, whilst leaving other cells unaffected.…”

Section: Delivery Techniques For Neurotrophin Administration In the Cmentioning

confidence: 99%

Neurotrophic Factors and Neural Prostheses: Potential Clinical Applications Based Upon Findings in the Auditory System

Pettingill

Richardson

Wise

et al. 2007

IEEE Trans. Biomed. Eng.

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Spiral ganglion neurons (SGNs) are the target cells of the cochlear implant, a neural prosthesis designed to provide important auditory cues to severely or profoundly deaf patients. The ongoing degeneration of SGNs that occurs following a sensorineural hearing loss is therefore considered a limiting factor in cochlear implant efficacy. We review neurobiological techniques aimed at preventing SGN degeneration using exogenous delivery of neurotrophic factors. Application of these proteins prevents SGN degeneration and can enhance neurite outgrowth. Furthermore, chronic electrical stimulation of SGNs increases neurotrophic factor-induced survival and is correlated with functional benefits. The application of neurotrophic factors has the potential to enhance the benefits that patients can derive from cochlear implants; moreover, these techniques may be relevant for use with neural prostheses in other neurological conditions.

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In Vitro and In Vivo Assessment of the Ability of Adeno‐Associated Virus–Brain‐Derived Neurotrophic Factor to Enhance Spiral Ganglion Cell Survival Following Ototoxic Insult

Cited by 46 publications

References 50 publications

Cochlear implants and ex vivo BDNF gene therapy protect spiral ganglion neurons

Cochlear implants and ex vivo BDNF gene therapy protect spiral ganglion neurons

Inner Ear Therapy for Neural Preservation

Neurotrophic Factors and Neural Prostheses: Potential Clinical Applications Based Upon Findings in the Auditory System

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