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Gene transfer with a vector expressing Maxi-K from a smooth muscle-specific promoter restores erectile function in the aging rat

Gene Therapy volume 15, pages 364–370 (2008)Cite this article

Abstract

Previous reports have demonstrated that gene transfer with the α, or pore-forming, subunit of the human Maxi-K channel (hSlo) restores the decline in erectile capacity observed in established rat models of diabetes and aging. Preliminary data from a human clinical trial also showed safety and potential efficacy in 11 men treated with the same plasmid construct expressing the Maxi-K channel. In all instances, the original plasmid was driven by the heterologous cytomegalovirus promoter which is broadly active in a wide variety of cell and tissue types. To more precisely determine the contribution of the corporal myocyte to the observed physiological effects in vivo, we report here our initial work using a distinct vector (pSMAA-hSlo) in which hSlo gene expression was driven off the mouse smooth muscle α-actin (SMAA) promoter. Specifically, older rats, with diminished erectile capacity, were given a single intracorporal injection with either 100 μg pVAX-hSlo or 10, 100 or 1000 μg pSMAA-hSlo, or vector or vehicle alone. Significantly increased intracavernous pressure (ICP) responses to cavernous nerve stimulation were observed for all doses of both plasmids encoding hSlo, relative to control injections. These data confirm and extend previous observations to document that smooth muscle cell-specific expression of hSlo in corporal tissue is both necessary and sufficient to restore erectile function in aging rats.

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Authors and Affiliations

  1. Department of Urology, Institute for Smooth Muscle Biology, Albert Einstein College of Medicine, Bronx, NY, USA

    A Melman, G Biggs, K Davies & M T Tar

  2. Wake Forest Institute for Regenerative Medicine, Wake Forest University Baptist Medical Center, Winston-Salem, NC, USA

    W Zhao & G J Christ

Authors
  1. A Melman
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  2. G Biggs
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  3. K Davies
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  4. W Zhao
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  5. M T Tar
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  6. G J Christ
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Correspondence to A Melman.

Additional information

Dr A Melman and Dr GJ Christ are founders and directing members of Ion Channel Innovations, LLC, the sponsor of the preclinical studies and clinical trial.

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Melman, A., Biggs, G., Davies, K. et al. Gene transfer with a vector expressing Maxi-K from a smooth muscle-specific promoter restores erectile function in the aging rat. Gene Ther 15, 364–370 (2008). https://doi.org/10.1038/sj.gt.3303093

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