Collagenase Clostridium histolyticum Treatment Improves Degree of Curvature in Peyronie’s Disease with Calcified Plaques

Masterson, Thomas A.; Atuluru, Pranusha; Zucker, Isaac; Molina, Mario García; Ibrahim, Emad; Nackeeran, Sirpi; Kava, Bruce R.; Ramasamy, Ranjith

doi:10.1016/j.euf.2022.09.019

Cited by 10 publications

(9 citation statements)

References 9 publications

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“…The here-obtained deeper mechanistic understanding of substrate selectivity paves the way for the design of collagenases with unprecedented specificities. Such uniquely specific enzymes can be used for various biotechnological applications in wound healing ( 43 ), oncolysis ( 44 ), the treatment of fibromatoses ( 45 , 46 ), and cosmetic surgery ( 47 ), to name a few.…”

Section: Discussionmentioning

confidence: 99%

A conserved strategy to attack collagen: The activator domain in bacterial collagenases unwinds triple-helical collagen

Serwanja,

Wieland,

Haubenhofer

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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Bacterial collagenases are important virulence factors, secreted by several pathogenic Clostridium , Bacillus , Spirochaetes , and Vibrio species. Yet, the mechanism by which these enzymes cleave collagen is not well understood. Based on biochemical and mutational studies we reveal that collagenase G (ColG) from Hathewaya histolytica recognizes and processes collagen substrates differently depending on their nature (fibrillar vs. soluble collagen); distinct dynamic interactions between the activator and peptidase domain are required based on the substrate type. Using biochemical and circular dichroism studies, we identify the presumed noncatalytic activator domain as the single-domain triple helicase that unwinds collagen locally, transiently, and reversibly.

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Section: Discussionmentioning

confidence: 99%

A conserved strategy to attack collagen: The activator domain in bacterial collagenases unwinds triple-helical collagen

Serwanja,

Wieland,

Haubenhofer

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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“…3,4 Of note, these findings (and our prior series) contrast to the Masterson report which may relate to differing classification schemes. 5 Finally, the current study was not designed (powered) to demonstrate superiority of one therapy over another. However, it clearly shows that collagenase C histolyticum would not be considered an inferior treatment, regardless of disease severity, and may be considered an equivalent gold standard when administered using optimal protocols.…”

Section: Reply By Authorsmentioning

confidence: 99%

“…3,4 Of note, these findings (and our prior series) contrast to the Masterson report which may relate to differing classification schemes. 5…”

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confidence: 99%

Reply by Authors

Green,

Flores,

Warner

et al. 2023

Journal of Urology

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event, but rather an expected outcome and one that may lead to less satisfaction even after extensive counseling from very experienced PD surgeons.The follow-up period for this publication was only 3 months. Although it is a short period of time, most adverse events should be captured; however, satisfaction may change more over time. We commend the authors on a well-designed and -executed study, and eagerly await the 1-and 5-year data.

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“…Results showed statistically significant improvement of 17.5° in patients and the improvement in curvature was not affected by the calcification grade (p<0.0001). 35 While these results are promising, 35% of patients were excluded from analysis as they withdrew from the study prior to receiving 8 injections for reasons including but not limited to difficulty in contact and dissatisfaction from minimal improvement.…”

Section: Introductionmentioning

confidence: 99%

Expanded Utilization of Intralesional Therapies for Treatment of Peyronie’s Disease

Khooblall¹,

Bole²,

Lundy³

et al. 2023

RRU

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Purpose In this narrative review we explore additional indications for which intralesional collagenase Clostridium histolyticum (CCH) injection therapy may be used, in addition to those utilized in the IMPRESS trials. The goal is to provide updated assessment of available intralesional therapies and justify whether to expand clinical indications based on advancements over the last decade. Results Patients receiving CCH in the acute phase of PD have shown significant improvement in penile curvature - which may be even more significant than reported due to progressive curvature over the longitudinal course of injection therapy. Across studies, patients with ventral plaques achieved the greatest curvature improvement (~30°) compared to PD patients with dorsal or lateral plaques. Patients with curvature > 90° have been minimally documented. However, the concept of patients with higher degree of curvature achieving more significant degrees of improvement prevails across studies. Studies including PD patients with volume loss deformities or indentation(s) focus on curvature improvement and do not gauge improvement in these girth loss or indentation features specifically. PD patients with calcification may benefit from CCH, however, critical analysis of included study designs and results compared to placebo do not lend for strong support of CCH in PD at this time. Conclusion Based on the most recent research, the use of CCH in the acute phase of PD and patients with ventral penile plaques may be effective and safe. The limited available research on the efficacy of CCH on calcified plaque(s) and curvature greater than 90° is promising, however, more research is needed to ensure safety and success in this patient cohort. Finally, the current literature continues to show the use of CCH is not effective in PD patients with volume loss, indentation, or hourglass deformity. When expanding the use of CCH to patients not originally included in the IMPRESS trials, providers must prioritize minimizing chances of potential injury to urethral tissue. Finally, further investigation is required to determine whether CCH has utility for curvature greater than 90° or calcified plaques, although the limited available literature is promising.

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Collagenase Clostridium histolyticum Treatment Improves Degree of Curvature in Peyronie’s Disease with Calcified Plaques

Cited by 10 publications

References 9 publications

A conserved strategy to attack collagen: The activator domain in bacterial collagenases unwinds triple-helical collagen

A conserved strategy to attack collagen: The activator domain in bacterial collagenases unwinds triple-helical collagen

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Expanded Utilization of Intralesional Therapies for Treatment of Peyronie’s Disease

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