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Human Reproduction Update Advance Access published online on April 7, 2006
Human Reproduction Update, doi:10.1093/humupd/dml015
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© The Author 2006. Published by Oxford University Press. on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org
Received August 10, 2005
Revised January 19, 2006
Accepted March 9, 2006

Review

Gene therapy and uterine leiomyoma: a review

Ayman Al-Hendy 1 * and Salama Salama 1

1 Department of Obstetrics & Gynecology, University of Texas Medical Branch, Galveston, TX, USA

* To whom correspondence should be addressed.
Ayman Al-Hendy, E-mail: ayalhend{at}utmb.edu


  Abstract

Leiomyomas (fibroids) are common estrogen-dependent uterine tumours that cause significant morbidity for women and a substantial economic impact on health delivery systems. Currently, there is no effective medical treatment option for this condition--hysterectomy is the mainstay of management. This is not an attractive choice for many women, especially patients desiring to preserve their fertility potential. Gene therapy is becoming a clinical reality, with more than 600 clinical trials worldwide. Researchers have recently attempted to develop a gene-therapy-based approach for the ablation of uterine fibroids. The localized nature of this condition and its accessibility using different imaging or endoscopic techniques make it an attractive target for direct delivery of gene-based vectors. Recent work from our laboratory suggests the potential use of a dominant-negative form of estrogen receptor (ER) to inactivate estrogen signalling in leiomyoma cells and induce apoptosis. Our in vivo data in a mouse model demonstrate the ability of an adenovirus-expressing dominant-negative ER to arrest leiomyoma growth. We and others also have described the utility of the herpes simplex virus-thymidine kinase (HSV-TK) plus ganciclovir (GCV) suicide gene-therapy system to effectively eradicate leiomyoma cells by utilizing the bystandard effect phenomena and the high expression of gap-junction protein in these tumours. Further work on rat models will pave the way for future leiomy-oma gene-therapy clinical trials and allow the realization of gene therapy as a viable non-surgical option for this common problem in women’s health.

Keywords: animal model/dominant-negative estrogen receptor/fibroids/gene therapy/uterine leiomyoma.
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