Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of clostridial collagenase on the tensile strength of Dupuytren's cords was studied in vitro to assess its potential efficacy as an agent for clinical enzymatic fasciotomy. Collagenase was injected into Dupuytren's cords from patients undergoing fascioctomy. Following a pilot experiment, in which a 3,600-unit dose of collagenase induced a 93% decrease in tensile modulus as compared with control cords, groups of five cords each were injected with 150, 300, and 600 units. These cords and a control group of five cords were tested by loading to failure in tension. The ultimate stress and strain to failure were recorded by a video capture technique. All specimens were stained for histologic examination with hematoxylin and eosin for collagen typing with sirrius red. Comparison of the ultimate stress values obtained with published values of extensor forces obtainable by the individual fingers of 40 normal hands indicated that a 300-unit dose of collagenase was sufficient for cord rupture within the average maximum force limits of the extensors of the index, long, ring, and small fingers (p < .02). All samples were in the residual disease stage histologically and contained type I collagen by sirrius red staining. These results indicate that collagenase may be effective in enzymatic fasciotomy of residual-stage Dupuytren's disease.
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PMID:Collagenase in the treatment of Dupuytren's disease: an in vitro study. 872 85

Many nonoperative therapies have been investigated for the treatment of Dupuytren's disease. These include needle fasciotomy, continuous slow skeletal traction, radiation, dimethyl sulfoxide, vitamin E, allopurinol, physical therapy, ultrasound therapy, steroid injections, radiation, interferon, splinting, and enzymatic fasciotomy. Most of these therapies have not proven to be clinically useful. However, recent investigation of enzymatic fasciotomy using collagenase injection has shown encouraging results.
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PMID:Nonoperative treatment of Dupuytren's disease. 1005 Feb 46

Surgical fasciectomy is the currently accepted treatment of Dupuytren's disease. The goal of this study was to test the clinical safety and efficacy of clostridial collagenase injection as a nonsurgical treatment of Dupuytren's disease in a phase II open-label trial. Thirty-five Dupuytren's disease patients entered the study (32 men and 3 women). The mean age was 65 years. The first 6 patients were treated following a dose escalation protocol and received 300, 600, 1,200, 2,400, 4,800, and 9,600 U collagenase injected into the cord that was causing contracture of the metacarpophalangeal (MCP) joint. There were no beneficial clinical effects of these injections. The remaining 29 patients had collagenase injections at a dose level of 10,000 U, causing contractures of 34 MCP joints, 9 proximal interphalangeal (PIP) joints, and 1 thumb. Twenty-eight of the 34 MCP joint contractures corrected to normal extension (0 degrees ) and 2 of the 34 MCP joint contractures corrected to 5 degrees of normal extension, with full range of motion, within 1 to 14 days of injection. In the patients with PIP joint contractures, 4 of the 9 joints corrected to normal (0 degrees ). One PIP joint corrected to within 10 degrees of normal and 2 corrected to within 15 degrees of normal. There were 2 failures; these patients will require surgery. The mean follow-up period was 20.0 +/- 5.6 months for the MCP joints and 14.1 +/- 6.6 months for the PIP joints. Clostridial collagenase injection of Dupuytren's cords causing MCP and PIP joint contractures appears to have merit as nonsurgical treatment of this disorder. Pending further placebo, double-blind studies, collagenase injection to treat Dupuytren's disease may be a safe and effective alternative to surgical fasciectomy.
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PMID:Enzyme injection as nonsurgical treatment of Dupuytren's disease. 1091 2

The cellular events leading to abnormal synthesis of collagen are important to our understanding of pathologic processes leading to impaired joint function. The contracture of Dupuytren's disease is a notable example. In a series of controlled phase-2 clinical trials, excessive collagen deposition in Dupuytren's disease has been targeted by a unique nonoperative method using enzyme (Clostridial collagenase) injection therapy to lyse and rupture finger cords causing metacarpophalangeal and/or proximal interphalangeal joint contractures. Forty-nine patients were treated in a random, placebo-controlled trial of one dose of collagenase versus placebo at one center. Subsequently 80 patients were treated in a random, placebo-controlled, dose-response study of collagenase at 2 test centers. The results of these studies indicate that nonoperative collagenase injection therapy for Dupuytren's disease is both a safe and effective method of treating this disorder in the majority of patients as an alternative to surgical fasciectomy. Phase-3 efficacy trials are now being planned to further develop and test this method under Food and Drug Administration regulatory guidelines. The findings of our study may lead to simpler and less invasive nonoperative treatments of joint limitation in which collagen plays a major pathologic role.
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PMID:Collagen as a clinical target: nonoperative treatment of Dupuytren's disease. 1223 66

Dupuytren's contracture is a fibroproliferative disorder characterized by progressive deposition of mature collagen fibers. In other fibrotic diseases affecting organs such as the liver, lung, heart, and skin, matrix metalloproteinases (MMPs) and their natural inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), play an important role. In this study, serum concentrations of MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 were determined in 22 patients (five women and 17 men; average age, 67 +/- 11 years) with Dupuytren's disease using an enzyme-linked immunosorbent assay. Tissue samples were obtained for standard histological and immunohistochemical analyses. Sera and samples of palmar fascia from 20 patients (13 women and seven men; average age, 60 +/- 15 years) who had undergone hand surgery for carpal tunnel syndrome were used as the control group. Statistical analysis was performed using the Mann-Whitney test. Patients with Dupuytren's contracture presented with a TIMP-1 concentration of 437 +/- 160 ng/ml, a significantly higher TIMP-1 concentration than that seen in the control patients, who had a concentration of 321 +/- 70 ng/ml (p < 0.05). Patients with a proliferative active disease (n = 14) had a significantly higher TIMP-1 concentration (525 +/- 136 ng/ml) than patients (n = 8) with a contracture in the late involutional and residual phase (286 +/- 41 ng/ml; p < 0.05). There were no significant differences in the TIMP-2, MMP-1, MMP-2, and MMP-9 serum concentrations between patients with palmar fibromatosis and the control group. Patients with Dupuytren's disease had a significantly lower MMP-to-TIMP ratio (1.1 +/- 0.3; p < 0.05) than the control group (1.5 +/- 0.35). Patients with an active palmar fibromatosis presented a significantly (p < 0.05) reduced ratio (1 +/- 0.2) compared with those in later phases (1.4 +/- 0.3). TIMP-1 and TIMP-2 could be detected in tissue of patients with Dupuytren's contracture, with an accumulation in proliferative areas. MMPs could be detected locally in Dupuytren's tissue in a few patients, with less positive staining than for TIMPs. In the control group, there was just little or no staining for TIMPs and MMPs. The data indicate that the physiological balance between MMPs and their natural inhibitors is disturbed in patients with a proliferative active Dupuytren's disease. The decrease in the systemic MMP-to-TIMP ratio can cause increased synthesis and deposition of collagen, leading to palmar fibromatosis.
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PMID:Matrix metalloproteinases and tissue inhibitors of metalloproteinases in sera and tissue of patients with Dupuytren's disease. 1450 11

Dupuytren's disease is a progress fibromatosis of unknown origin first described in 1831. Nonoperative treatment options have been suggested involving radiation therapy, vitamin E, local injection therapy suing calcium channel blockers, interferon, corticosteroids or collagenase. Transforming growth factor-beta1 (TGF-beta1) and its downstream Smad signalling system is well established as a key player during fibrogenesis. A number of in vitro experiments have been assessed the blockade of TGF-beta1 and TGF-beta 2. Clinically, a number of antifibrotic agents are available such as N-acetyl-L-cysteins (NAC) as well as angiotensin-converting enzyme (ACE) inhibitors or AT II antagonists. However, to date none of the well known substances has been tested clinically in fibromatosis such as Dupuytren's disease especially to prevent recurrences after surgical release. Antifibrotic medication using a combination of N-acetyl-L-cystein (NAC) and ACE inhibitor can prevent the recurrence of Dupyutren's disease. Given the fact that recurrence rate in Dupuytren's disease is high and unpredictable after surgical release, an antifibrotic intervention might be worthwhile to consider in the clinical setting. Antifibrotic agents inhibit TGF-beta1, which play a key role in fibromatosis. Thus, antifibrotic medication might reduce the recurrence rate in fibromatosis such as Dupuytren's disease in a clinical significant way.
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PMID:Antifibrotic medication using a combination of N-acetyl-L-cystein (NAC) and ACE inhibitors can prevent the recurrence of Dupuytren's disease. 1972 37

In this article we systematically review treatment options for Dupuytren's contracture. There is little evidence on the effectiveness of many treatment modalities for Dupuytren's disease other than expert's opinions (level 4). Most hand surgeons perform selective fasciectomy for Dupuytren's disease. Because of its lower recurrence rate, dermofasciectomy is increasingly being performed to treat recurrences. Percutaneous needle fasciotomy is a minimally invasive treatment with good short-term results in patients with mild to moderate contractures, but it has a high recurrence rate. Radiotherapy and the use of collagenase are promising, but their role in treating Dupuytren's disease is still unclear.
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PMID:[Treatment of Dupuytren's contracture; an overview of options]. 1985 98

Collagenase clostridium histolyticum is a novel treatment for Dupuytren's contracture, approved by the U.S. Food and Drug Administration in February 2010. Prior to its availability, surgery was the only treatment for contracture related to this disorder. Dupuytren's disease is a benign, progressive fibroproliferative disorder affecting the palms of the hands. It is characterized by the formation of collagen- rich nodules and cords, which gradually shorten by the action of myofibroblasts, resulting in finger contractures. Intralesional use of clostridial collagenase has been evaluated in a total of 1,082 patients receiving 2,630 injections during its clinical development, including 2 large prospective, randomized, double-blind, placebo-controlled trials: Collagenase Option for Reduction of Dupuytren's I (CORD I) and CORD II. Both studies showed a statistically significant reduction in contracture compared to placebo and treatment was well-tolerated with the majority of adverse events self-limited. Serious adverse events related to collagenase activity were rare. Maximal improvement was seen in patients with less severe contractures and with contractures of the metacarpophalangeal joint. This first-in-class biologic, injectable clostridial collagenase histolyticum, provides a safe, effective alternative to surgery for patients with Dupuytren's contracture.
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PMID:Collagenase clostridium histolyticum injection for the treatment of Dupuytren's contracture. 2197 40

Dupuytren's disease is a benign contractile disorder of the hand. The condition commonly affects older men of Celtic descent. Although fibroproliferation and collagen alteration play a role in its etiology, defining a cause remains elusive. Nonoperative intervention for advanced disease has shown only short-term benefit. Therefore, open fasciectomy has become the mainstay of treatment. Associated morbidity and recurrence have prompted investigation into less invasive techniques, including needle aponeurotomy and enzymatic fasciotomy. Data from phase III studies using injectable collagenase are changing treatment algorithms. Postoperative rehabilitation includes nighttime splinting and immediate active range of motion exercises to facilitate return to function.
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PMID:Dupuytren's disease. 2222 22

Dupuytren's disease is a fibroproliferative disease of the palmar fascia which has been described for centuries, yet the aetiology and pathophysiology remain poorly understood. Surgery and collagenase injections comprise the main therapeutic options but disease recurrence is common. We explore the evidence underlying the current disease theories and outline other potential therapeutic options.
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PMID:Advances in the understanding of the aetiology of Dupuytren's disease. 2229 48


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