PMID- 25809464
OWN - NLM
STAT- MEDLINE
DCOM- 20160112
LR  - 20181113
IS  - 1476-5462 (Electronic)
IS  - 0969-7128 (Linking)
VI  - 22
IP  - 7
DP  - 2015 Jul
TI  - Cochlear protection against cisplatin by viral transfection of X-linked inhibitor 
      of apoptosis protein across round window membrane.
PG  - 546-52
LID - 10.1038/gt.2015.22 [doi]
AB  - We have previously demonstrated that both age-related and noise-induced hearing 
      loss are reduced in transgenic mice that ubiquitously overexpress X-linked 
      inhibitor of apoptosis protein (XIAP). In view of the therapeutic implications of 
      these findings, we have developed a minimally invasive surgical method to deliver 
      adenoid-associated virus (AAV) across the round window membrane (RWM) of the 
      cochlea, enabling efficient gene transfer to hair cells and sensory neurons in 
      this enclosed structure. This RWM approach was used in the present study to 
      evaluate the effectiveness of AAV-mediated XIAP overexpression in protecting 
      against cisplatin-induced ototoxicity. Two weeks following surgery, AAV-derived 
      XIAP was detected in the majority of inner and outer hair cells, resulting in a 
      threefold elevation of this antiapoptotic protein in the cochlea. The protection 
      of AAV-mediated XIAP overexpression was evaluated in animals treated with 
      cisplatin at a dose of 4 mg kg(-1) per day for 4-7 consecutive days. The XIAP 
      overexpression was found to attenuate cisplatin-induced hearing loss by ~22 dB. 
      This was accompanied by a reduction of the loss of vulnerable hair cells and 
      sensory neurons in the cochlea by 13%.
FAU - Jie, H
AU  - Jie H
AD  - Department of Otolaryngology, Affiliated Sixth People's Hospital of Shanghai Jiao 
      Tong University, Shanghai, China.
FAU - Tao, S
AU  - Tao S
AD  - Department of Physiology, Medical College, Southeast University, Nanjing, China.
FAU - Liu, L
AU  - Liu L
AD  - Department of Physiology, Medical College, Southeast University, Nanjing, China.
FAU - Xia, L
AU  - Xia L
AD  - Department of Otolaryngology, Affiliated Sixth People's Hospital of Shanghai Jiao 
      Tong University, Shanghai, China.
FAU - Charko, A
AU  - Charko A
AD  - School of Human Communication Disorder, Dalhousie University, Halifax, Nova 
      Scotia, Canada.
FAU - Yu, Z
AU  - Yu Z
AD  - School of Human Communication Disorder, Dalhousie University, Halifax, Nova 
      Scotia, Canada.
FAU - Bance, M
AU  - Bance M
AD  - Department of Surgery, Division of Otolaryngology, Dalhousie University, Halifax, 
      Nova Scotia, Canada.
FAU - Yin, S
AU  - Yin S
AD  - Department of Otolaryngology, Affiliated Sixth People's Hospital of Shanghai Jiao 
      Tong University, Shanghai, China.
FAU - Robertson, G S
AU  - Robertson GS
AD  - Departments of Psychiatry and Pharmacology, Dalhousie University, Halifax, Nova 
      Scotia, Canada.
FAU - Wang, J
AU  - Wang J
AUID- ORCID: 0000000336336799
AD  - 1] Department of Otolaryngology, Affiliated Sixth People's Hospital of Shanghai 
      Jiao Tong University, Shanghai, China [2] School of Human Communication Disorder, 
      Dalhousie University, Halifax, Nova Scotia, Canada.
LA  - eng
PT  - Journal Article
DEP - 20150326
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (Antineoplastic Agents)
RN  - 0 (X-Linked Inhibitor of Apoptosis Protein)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*toxicity
MH  - Cisplatin/*toxicity
MH  - Cochlea/*drug effects/metabolism
MH  - Dependovirus/genetics/*metabolism
MH  - Genetic Therapy/methods
MH  - Genetic Vectors
MH  - Guinea Pigs
MH  - Hair Cells, Auditory/metabolism
MH  - Hearing Loss/*chemically induced/*prevention & control
MH  - Round Window, Ear/metabolism
MH  - Sensory Receptor Cells/metabolism
MH  - Transfection
MH  - X-Linked Inhibitor of Apoptosis Protein/genetics/*metabolism
EDAT- 2015/03/27 06:00
MHDA- 2016/01/13 06:00
CRDT- 2015/03/27 06:00
PHST- 2014/11/03 00:00 [received]
PHST- 2015/02/15 00:00 [revised]
PHST- 2015/02/18 00:00 [accepted]
PHST- 2015/03/27 06:00 [entrez]
PHST- 2015/03/27 06:00 [pubmed]
PHST- 2016/01/13 06:00 [medline]
AID - gt201522 [pii]
AID - 10.1038/gt.2015.22 [doi]
PST - ppublish
SO  - Gene Ther. 2015 Jul;22(7):546-52. doi: 10.1038/gt.2015.22. Epub 2015 Mar 26.