title: Injectable Clostridium histolyticum collagenase as a potential treatment for uterine fibroids.
abstract: Purified Clostridium histolyticum collagenase (CHC), an Food and Drug Administration-approved drug that does not affect nerves or blood vessels, was assessed as a potential treatment for fibroids in this proof-of-principle study. Fibroids (1-4 cm, capsules intact) and myometrial specimens from 5 patients were injected posthysterectomy with CHC or vehicle containing methylene blue and incubated for 24 hours. Percentage of collagen-stained area was estimated using Masson-Trichrome-stained slides. Collagen fibers were observed with picrosirius staining. Tissue stiffness was objectively measured by rheometry (complex shear modulus [Pa]). Injected materials spread within and beyond fibroids as visualized by methylene blue. Of the 8 treated fibroids, 7 were softened and some contained liquefied centers. Relative percentage of collagen-stained area (mean ± standard deviation) in treated fibroids (38 ± 12%; n = 7) was less than that in control fibroids (66 ± 17%; n = 5). Treated myometrium (40 ± 30% collagen; n = 3) was similar to control myometrium (53 ± 8%; n = 2). Picrosirius staining demonstrated loss of collagen fibers in treated fibroids. Treated fibroids were less stiff (3630 ± 2410 Pa; n = 4) than controls (5930 ± 830 Pa; n = 4). Treated and control myometrium had similar stiffness (2149 ± 927 Pa; n = 3 and 3314 ± 494 Pa; n = 2, respectively) and were never liquefied. In conclusion, injections of CHC into encapsulated fibroids are feasible and effective. Heterogeneity of collagen types and quantities within individual fibroids may contribute to varied responses and need additional investigation. Further study of collateral effects on myometrium is indicated. Injected CHC has potential for treatment of fibroids.
authors.affiliation: Department of Obstetrics and Gynecology, Duke University Medical Center, Reproductive Biology and Perinatal Laboratory, Durham, NC, USA lisa.brunengraber@gmail.com.
authors.forename: Lisa N
authors.initials: LN
authors.lastname: Brunengraber
authors.affiliation: Department of Obstetrics and Gynecology, Duke University Medical Center, Reproductive Biology and Perinatal Laboratory, Durham, NC, USA Department of Pathology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Friederike L
authors.initials: FL
authors.lastname: Jayes
authors.affiliation: Department of Obstetrics and Gynecology, Duke University Medical Center, Reproductive Biology and Perinatal Laboratory, Durham, NC, USA Department of Pathology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Phyllis C
authors.initials: PC
authors.lastname: Leppert
mesh_terms: D047009:Hathewaya histolytica / Q000201:enzymology*; D055119:Elastic Modulus; D005240:Feasibility Studies; D005260:Female; D024022:Fibrillar Collagens / Q000378:metabolism; D006801:Humans; D015552:Injections, Intralesional; D007889:Leiomyoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003012:Microbial Collagenase / Q000008:administration & dosage* / Q000302:isolation & purification; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D046509:Tissue Culture Techniques; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D024022:Fibrillar Collagens; D003012:Microbial Collagenase
keywords: clostridium; clostridium histolyticum; collagenase; fibroid; leiomyoma