Experimental chemonucleolysis with recombinant human matrix metalloproteinase 7 in human herniated discs and dogs

Haro, Hirotaka; Nishiga, Miyuki; Ishii, Daisuke; Shimomoto, Takasumi; Kato, Tsuyoshi; Takenouchi, Osami; Koyanagi, Satoru; Ohba, Tetsuro; Komori, Hiromichi

doi:10.1016/j.spinee.2013.11.039

Cited by 9 publications

(9 citation statements)

References 35 publications

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“…It appeared to have no effect on collagen fibers, neurons, axons, myelin sheaths, or astrocytes, as well as no systemic effects after both 1 and 13 weeks 42. In addition, because recombinant human MMP-7 is a human protein, there will likely be no anaphylaxis with its use clinically 42. At this point, MMP-7 appears to be a safe alternative to chymopapain although definitive studies need to be conducted to prove this in humans.…”

Section: Introductionmentioning

confidence: 97%

“…After injecting radioactive recombinant human MMP-7, it was not found in the muscle or surrounding tissues when applied correctly in canines. It appeared to have no effect on collagen fibers, neurons, axons, myelin sheaths, or astrocytes, as well as no systemic effects after both 1 and 13 weeks 42. In addition, because recombinant human MMP-7 is a human protein, there will likely be no anaphylaxis with its use clinically 42.…”

Section: Introductionmentioning

confidence: 99%

“…MMPs are neutral secreted zinc proteases that have been shown to degrade various portions of the extracellular matrix 3,4. It appears that MMP-7 cleaves aggrecan molecules at 1000-fold the strength of collagen type I or II 42. This means that the NP, which is comprised mainly of proteoglycans and type II collagen, would likely be the most affected portion.…”

Section: Introductionmentioning

confidence: 99%

“…While MMP-7 appeared to only degrade the structures of the nucleus, chymopapain exhibited destruction of both the nucleus and the annulus. This means that unlike chemonucleolysis with chymopapain, MMP-7 may facilitate resorption for all types of herniated discs (i.e., protrusion and extrusion) with negligible effects on surrounding structures 42,45. After injecting radioactive recombinant human MMP-7, it was not found in the muscle or surrounding tissues when applied correctly in canines.…”

Section: Introductionmentioning

confidence: 99%

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Treatment of chronic low back pain – new approaches on the horizon

Knežević¹,

Mandalia²,

Raasch³

et al. 2017

JPR

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Back pain is the second leading cause of disability among American adults and is currently treated either with conservative therapy or interventional pain procedures. However, the question that remains is whether we, as physicians, have adequate therapeutic options to offer to the patients who suffer from chronic low back pain but fail both conservative therapy and interventional pain procedures before they consider surgical options such as discectomy, disc arthroplasty, or spinal fusion. The purpose of this article is to review the potential novel therapies that are on the horizon for the treatment of chronic low back pain. We discuss medications that are currently in use through different phases of clinical trials (I–III) for the treatment of low back pain. In this review, we discuss revisiting the concept of chemonucleolysis using chymopapain, as the first drug in an intradiscal injection to reduce herniated disc size, and newer intradiscal therapies, including collagenase, chondroitinase, matrix metalloproteinases, and ethanol gel. We also review an intravenous glial cell-derived neurotrophic growth factor called artemin, which may repair sensory nerves compressed by herniated discs. Another new drug in development for low back pain without radiculopathy is a subcutaneous monoclonal antibody acting as nerve growth factor called tanezumab. Finally, we discuss how platelet-rich plasma and stem cells are being studied for the treatment of low back pain. We believe that with these new therapeutic options, we can bridge the current gap between conservative/interventional procedures and surgeries in patients with chronic back pain.

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Treatment of chronic low back pain – new approaches on the horizon

Knežević¹,

Mandalia²,

Raasch³

et al. 2017

JPR

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“…The results of animal and human studies have shown the important role of MMPs in the development of disc degeneration and NP, which indicates that MMPs are a possible target for therapeutic interventions 13. This is of particular interest because conventional treatments are disappointing in chronic low back pain management.…”

Section: Introductionmentioning

confidence: 99%

<p>The impact of changes in serum levels of metalloproteinase-2 and metalloproteinase-9 on pain perception in patients with disc herniation before and after surgery</p>

Kamieniak

Bielewicz

Kurzepa

et al. 2019

JPR

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Purpose: The aim of our research was to investigate the link between serum levels of metalloproteinase-2 (MMP-2) and MMP-9, and the degree of pain experienced before and 1 and 3 months after microdiscectomy in 70 patients with disc herniation (DH). Patients and methods: The control group (group C) consisted of 70 healthy subjects and the DH group consisted of 70 patients with sciatica pain caused by lumbar DH. Before (DH0) and 1 and 3 months after surgery, the patients were assessed in terms of the following biochemical parameters: MMP-2, tissue inhibitors of metalloproteinases-2 (TIMP-2), MMP-2/TIMP-2, MMP-9, TIMP-1, and MMP-9/TIMP1, and the following clinical parameters: Numeric Rating Scale for the back (NRS-B) and the leg (NRS-L) and the Pain Rating Index (PRI) and Present Pain Intensity (PPI) of the McGill Pain Questionnaire. Results: No statistically significant correlations were observed following the biochemical and clinical assessments performed in group C and the DH group before surgery. After surgery (1 month), higher levels of TIMP-1 correlated with higher levels of NRS-B (rs =0.27; p <0.05). At 3 months after surgery higher levels of TIMP-2 and lower levels of MMP-2/TIMP-2 were correlated with higher levels of NRS-L (rs =0.27, p <0.05 and rs =−0.31, p <0.05, respectively) and higher levels of TIMP-2 were correlated with higher PRI scores (rs =0.27; p <0.005) and PPI scores (rs =0.35; p <0.01). Conclusion: The results showed that MMPs are involved in DH and play a significant role in the perception of pain after DH surgery. However, the value of MMPs as a potential therapeutic target in pain treatment should be considered cautiously.

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An Analysis of New Approaches and Drug Formulations for Treatment of Chronic Low Back Pain

Bhangare

Kaye

Knezevic

et al. 2017

Anesthesiology Clinics

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Experimental chemonucleolysis with recombinant human matrix metalloproteinase 7 in human herniated discs and dogs

Cited by 9 publications

References 35 publications

Treatment of chronic low back pain – new approaches on the horizon

Treatment of chronic low back pain – new approaches on the horizon

<p>The impact of changes in serum levels of metalloproteinase-2 and metalloproteinase-9 on pain perception in patients with disc herniation before and after surgery</p>

An Analysis of New Approaches and Drug Formulations for Treatment of Chronic Low Back Pain

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Experimental chemonucleolysis with recombinant human matrix metalloproteinase 7 in human herniated discs and dogs

Cited by 9 publications

References 35 publications

Treatment of chronic low back pain &ndash;&nbsp;new approaches on the horizon

Treatment of chronic low back pain &ndash;&nbsp;new approaches on the horizon

<p>The impact of changes in serum levels of metalloproteinase-2 and metalloproteinase-9 on pain perception in patients with disc herniation before and after surgery</p>

An Analysis of New Approaches and Drug Formulations for Treatment of Chronic Low Back Pain

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Product

Resources

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Treatment of chronic low back pain – new approaches on the horizon

Treatment of chronic low back pain – new approaches on the horizon