Gene therapy using replication-defective herpes simplex virus vectors expressing nerve growth factor in a rat model of diabetic cystopathy

Katsumi Sasaki, Michael B. Chancellor, William F. Goins, Michael W. Phelan, Joseph C. Glorioso, William C. De Groat, Naoki Yoshimura

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Abstract

Diabetic cystopathy is one of the common complications of diabetes and current therapy is limited. In the present study, the effects of gene therapy, using replication-defective herpes simplex virus type 1 (HSV-1) vectors to deliver and express the nerve growth factor (NGF) gene (HSV-NGF) on tissue NGF levels and bladder function, were evaluated in streptozotocin (STZ)-induced diabetic rats. Diabetic rats exhibited a significant decrease in NGF levels in the bladder and lumbosacral dorsal root ganglia (DRG) detected by enzyme-linked immunosorbent assay and displayed marked bladder dysfunction 12 weeks after STZ injection. In contrast, rats with bladder wall injection of the NGF expression vector 8 weeks after STZ treatment exhibited a significant increase of NGF levels in the bladder and L6 DRG 4 weeks after HSV-NGF injection. Along with the restoration of tissue NGF expression, in metabolic cage studies and cystometry, HSV-NGF-injected rats also showed significantly reduced bladder capacity and postvoid residual volume than diabetic rats injected with the control vector (HSV-lacZ), indicating that voiding function was improved after HSV vector-mediated NGF gene delivery. Thus, HSV vector-mediated NGF gene therapy may prove useful to restore decreased NGF expression in the bladder and bladder afferent pathways, thereby improving hypoactive bladder function in diabetes.

Original languageEnglish
Pages (from-to)2723-2730
Number of pages8
JournalDiabetes
Volume53
Issue number10
DOIs
Publication statusPublished - Oct 1 2004

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Sasaki, K., Chancellor, M. B., Goins, W. F., Phelan, M. W., Glorioso, J. C., De Groat, W. C., & Yoshimura, N. (2004). Gene therapy using replication-defective herpes simplex virus vectors expressing nerve growth factor in a rat model of diabetic cystopathy. Diabetes, 53(10), 2723-2730. https://doi.org/10.2337/diabetes.53.10.2723