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In vitro efficacy of intralesional Collagenase Clostridium Histolyticum for the treatment of calcified Peyronie’s disease plaques

International Journal of Impotence Research (2023)Cite this article

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Abstract

Peyronie’s disease (PD) is defined by penile plaque formation and curvature causing sexual dysfunction. The only FDA-approved intralesional treatment is Collagenase Clostridium histolyticum (CCh). CCh contains two collagenases, AUX1 and AUXII, that break down the type I and type III collagen contained in plaques, leading to plaque dissolution and reduction in penile curvature. Peyronie’s plaques, however, also contain fibrin and calcium, which CCh cannot digest. It is unclear if plaque calcification prevents CCh from breaking down plaques. We collected ten tissue samples: five calcified penile plaques and five control samples of corpus cavernosum. They were incubated in CCh or PBS. Soluble collagen measurements and collagen staining assays were completed to measure tissue breakdown. Calcified plaques incubated in CCh showed significantly higher levels of soluble collagen (301.07 ug ± 21.28 vs. PBS: 32.82 ug ± 3.68, p = 0.02), and significantly lower levels of collagen (type I and III) compared to tissues incubated in PBS (0.12 ± 0.08, vs. 0.44 ± 0.17, p = 0.002). When comparing different tissues (calcified vs. control) incubated in CCh and PBS solutions, there were no significant differences in collagen staining or breakdown. Although higher collagen staining was seen in the calcified group, soluble collagen showed no significant differences between control and calcified tissues in the CCh group (control: 0.08 ± 0.02 vs. calcified: 0.17 ± 0.09, p = 0.08) or the PBS group (control: 0.50 ± 0.23 vs. calcified: 0.39 ± 0.39, p = 0.23). CCh exposure led to significantly more tissue breakdown in both tissue groups when compared to PBS however, there was no significant difference in plaque digestion found between calcified and control tissue exposed to CCh or PBS. This suggests that plaque calcification does not affect the action of CCh. Further research into CCh for calcified plaques is necessary to inform clinicians as to the optimal management of this population.

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Fig. 1: Polarized light photos of collagen staining in different experimental conditions.

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Funding

Collagenase Clostridium Histolyticum (CCh) was provided by the manufacturer Endo Pharmaceuticals.

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Authors and Affiliations

  1. Desai Sethi Urology Institute, University of Miami, 1150 NW 14th St, Miami, FL, 33136, USA

    Alexandra Dullea, Kajal Khodamoradi, Katherine Campbell, Ranjith Ramasamy & Thomas Masterson

  2. Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th St, Miami, FL, 33199, USA

    Armin Ghomeshi

  3. Department of Urology, Mayo Clinic, Rochester, MN, 55902, USA

    Matthew Ziegelmann

Authors
  1. Alexandra Dullea
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  2. Kajal Khodamoradi
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  3. Katherine Campbell
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  4. Armin Ghomeshi
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  5. Ranjith Ramasamy
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  6. Matthew Ziegelmann
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  7. Thomas Masterson
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Contributions

AD: designing and performing the experiments, statistical analysis. KK: designing and performing the experiments, statistical analysis. KC: drafting and editing the manuscript. AG: drafting the manuscript. RR: funding support, designing the experiments. MZ: designing and performing the experiments, editing the manuscript. TM: conceiving of and designing the experiments, funding support, drafting and editing the manuscript.

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Correspondence to Thomas Masterson.

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Dullea, A., Khodamoradi, K., Campbell, K. et al. In vitro efficacy of intralesional Collagenase Clostridium Histolyticum for the treatment of calcified Peyronie’s disease plaques. Int J Impot Res (2023). https://doi.org/10.1038/s41443-023-00742-0

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  • DOI: https://doi.org/10.1038/s41443-023-00742-0

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