Viability of Long-Term Gene Therapy in the Cochlea

被引：15

作者：

Atkinson, Patrick J. ^{[1
,2
]}

Wise, Andrew K. ^{[1
,2
,4
]}

Flynn, Brianna O. ^{[1
]}

Nayagam, Bryony A. ^{[1
,3
]}

Richardson, Rachael T. ^{[1
,2
,4
]}

机构：

[1] Bion Inst, East Melbourne, Vic, Australia

[2] Univ Melbourne, Dept Otolaryngol, East Melbourne, Vic, Australia

[3] Univ Melbourne, Dept Audiol & Speech Pathol, Parkville, Vic 3052, Australia

[4] Univ Melbourne, Dept Med Bion, East Melbourne, Vic, Australia

来源：

SCIENTIFIC REPORTS | 2014年 / 4卷

基金：

英国医学研究理事会;

关键词：

SPIRAL GANGLION-CELLS; NEUROTROPHIC FACTOR; PARKINSONS-DISEASE; SURVIVAL; HEARING; NEURONS; IMPROVEMENT; CESSATION; MODEL; BDNF;

D O I：

10.1038/srep04733

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Gene therapy has been investigated as a way to introduce a variety of genes to treat neurological disorders. An important clinical consideration is its long-term effectiveness. This research aims to study the long-term expression and effectiveness of gene therapy in promoting spiral ganglion neuron survival after deafness. Adenoviral vectors modified to express brain derived neurotrophic factor or neurotrophin-3 were unilaterally injected into the guinea pig cochlea one week post ototoxic deafening. After six months, persistence of gene expression and significantly greater neuronal survival in neurotrophin-treated cochleae compared to the contralateral cochleae were observed. The long-term gene expression observed indicates that gene therapy is potentially viable; however the degeneration of the transduced cells as a result of the original ototoxic insult may limit clinical effectiveness. With further research aimed at transducing stable cochlear cells, gene therapy may be an efficacious way to introduce neurotrophins to promote neuronal survival after hearing loss.

引用

页数：6

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