Treatment of endometriosis with a VEGF-targeted conditionally replicative adenovirus

Daniel T. Rein, Torsten Schmidt, Gerd Bauerschmitz, Monika Hampl, Ines M. Beyer, Arasen A.V. Paupoo, David T. Curiel, Martina Breidenbach

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Objective: To evaluate a vascular endothelial growth factor (VEGF)-targeted gene therapy for the treatment of endometriosis. Design: Analysis of the VEGF gene expression and promoter activity in ectopic and eutopic endometrium. Evaluation of the specific replication and cell-killing effect of a VEGF-targeted adenovirus (Ad5VEGFE1) in endometriotic cells. Patient(s): Four patients who underwent hysterectomy for benign disease, 30 women with moderate superficial, and 30 women with deep infiltrating endometriosis. Intervention(s): Immunostaining and gene expression of VEGF was examined in eutopic endometrium, endometriotic lesions, and normal peritoneum. The VEGF promoter activity was evaluated in eutopic endometrium and endometriotic lesions. A VEGF-targeted conditionally replicative adenovirus (Ad5VEGFE1) was evaluated regarding specific viral replication in endometriosis cells and induction of apoptosis. The biodistribution of the VEGF-targeted conditionally replicative adenovirus was examined in a mouse model. Result(s): The VEGF gene was highly expressed in ectopic endometrium compared with eutopic endometrium and normal peritoneum. The VEGF promoter was active in endometriotic cells. Ad5VEGFE1 showed efficient viral replication and induction of apoptosis in purified primary endometriotic cells and demonstrated a similar lower targeting to the liver and the uterus in a mouse model. Conclusion(s): Ad5VEGFE1 is a promising candidate for treating endometriosis and holds potential for clinical testing.

Original languageEnglish
Pages (from-to)2687-2694
Number of pages8
JournalFertility and Sterility
Volume93
Issue number8
DOIs
StatePublished - May 15 2010

Keywords

  • Endometriosis
  • gene therapy
  • replicating adenovirus
  • targeting

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