The Matrix Metalloproteinases Panel in Multiple Sclerosis Patients Treated with Natalizumab: A Possible Answer to Natalizumab Non- Responders

Bălaşa, Rodica; Septimiu, Voidezan; Simu, Iunius; Adina, Hutanu; Sebastian, Andone; Romaniuc, Anatole; Moţăţăianu, Anca; Maier, Smaranda

doi:10.2174/1871527317666180703102536

Cited by 14 publications

(7 citation statements)

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“…In 2020, the effect of natalizumab use on MMPs in a mouse model was studied and the results showed that natalizumab significantly reduced the expression of MMPs and that their tissue inhibitors (TIMPs) were upregulated [ 39 ]. Another study on natalizumab showed that this drug significantly decreases the levels of MMP-9, MMP-2, MMP-3, MMP-8, and MMP-10 when used in humans [ 40 ]. As most of the therapeutics used to treat MS target the peripheral immune response, a current approach is to target disease-promoting processes, such as the reduction of MMPs.…”

Section: Discussionmentioning

confidence: 99%

Expression of Inflammatory Mediators in Biofilm Samples and Clinical Association in Multiple Sclerosis Patients in Remission—A Pilot Study

Fehlhofer,

Ries,

Nickel

et al. 2024

Life

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Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of unknown etiology that affects the central nervous system and can lead to neurological impairment. Our aim was to determine whether MS patients also show inflammatory changes in the oral cavity more frequently than healthy individuals. For this purpose, we examined plaque samples for various mediators and their correlation with clinical findings. A study group (MS) and a control group were examined and compared. The plaque samples were analyzed for the expression of interleukins (IL-2, -6, -10), matrix metalloproteinases (MMP-7, MMP-9), and a surface antigen CD90 by quantitative real-time PCR. The clinical parameters examined were the Mombelli plaque index; bleeding on probing (BOP) index; periodontal pocket depth; and decayed, missing, and filled tooth (DMFT) index. The expression of MMP9 was significantly (p = 0.035) higher in the control group. The expression of IL-2 was increased four-fold in the MS group; however, this difference was not statistically significant. The mean PD (p < 0.001) and BOP index (p = 0.029) values were increased in the study group. The clinical parameters of the BOP index and PD were significantly amplified in the MS patients. However, no causal relationship between the investigated inflammatory mediators and the clinical findings could be established in this case series.

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Section: Discussionmentioning

confidence: 99%

Expression of Inflammatory Mediators in Biofilm Samples and Clinical Association in Multiple Sclerosis Patients in Remission—A Pilot Study

Fehlhofer,

Ries,

Nickel

et al. 2024

Life

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“…A possible response to NTZ treatment has also been explored. Balasa and coworkers reported a significant decrease in serum MMP-9 after 8 months of treatment and a good correlation between the biomarker and disease activity [155] , but this finding was not confirmed by other studies [156] . In NTZ-treated patients, decreased baseline levels of MMP-9 were found in patients who developed progressive multifocal leukoencephalopathy compared with those who did not [157] .…”

Section: Mmp-9mentioning

confidence: 82%

CSF biomarkers in multiple sclerosis: beyond neuroinflammation

Toscano¹,

Patti²

2020

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For many years, quantifiable biomarkers in neurological diseases have represented a hot topic. In multiple sclerosis (MS), cerebrospinal fluid biomarkers have played a diagnostic role since the introduction of Poser's criteria in 1983, with IgG oligoclonal bands playing a supporting role in an epoch prior to magnetic resonance imaging and a complementary one after the introduction of McDonald criteria in 2001. Nowadays, that supporting role has turned into a main one in substituting for dissemination in time and defining the diagnosis of MS in patients with a first clinical event, according to the 2017 revised McDonald criteria. Possibly kappa free light chains, N-CAM, chitinase 3-like protein 1 and IgM oligoclonal bands, not yet implemented in clinical practice, could similarly gain importance in the near future. Furthermore, the increasing knowledge of molecular mechanisms leading to chronic inflammation has enhanced interest in looking for biomarkers of disease activity, better defining the MS phenotype and patients with highly active disease. Accordingly, myelin proteins, intermediate filaments, metalloproteinases and other molecules involved in the inflammatory cascade, are currently under investigation. Finally, it has long been known that axonal loss occurs from the early phases, leading to a progressive neurological deterioration. Since established criteria to assess treatment failure and transition to progressive forms are still lacking, both treatment response and prognostic biomarkers would be useful to predict MS course, and neurofilaments seem to have this potential. The purpose of this review article was to illustrate biomarkers that have been already validated or require further validation after proving to be useful in exploratory studies and potentially could prove useful in clinical practice in the coming years.

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“…In 2020, the effect of natalizumab use on MMPs in a mouse model was studied, and the results showed that natalizumab signi cantly reduced the expression of MMPs and that their tissue inhibitors (TIMPs) were upregulated (38). Another study on natalizumab showed that this drug signi cantly decreases the levels of MMP-9, MMP-2, MMP-3, MMP-8 and MMP-10 when used in humans (39). As most of the therapeutics used to treat MS target the peripheral immune response, a current approach is to target disease-promoting processes such as the reduction of MMPs.…”

Section: Discussionmentioning

confidence: 99%

Expression of inflammatory mediators in biofilm samples and clinical association in multiple sclerosis patients in remission – a pilot study of case series

Fehlhofer

Ries

Nickel

et al. 2023

Preprint

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Background: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of unknown etiology that affects the central nervous system and can lead to neurological impairment. Our aim was to determine whether MS patients also show inflammatory changes in the oral cavity more frequently than healthy individuals. Material and Methods: We examined plaque samples for various mediators and their correlation with clinical findings. A study group (MS) and a control group were examined and compared. The plaque samples were analyzed for the expression of interleukins (IL-2, -6, -10), matrix metalloproteinases (MMP-7, MMP-9) and a surface antigen CD90 by quantitative real-time PCR. Clinical parameters examined were the Mombelli plaque index (MPI), bleeding on probing (BOP) index, gingival pocket depth (PD) and Decayed, missing and filled tooth (DMFT) index. Results: The expression of MMP9 was significantly (p=0.035) higher in the control group. The expression of IL-2 was increased 4-fold in the MS group, but this difference was not statistically significant. The mean PD (p<0.001) and BOP index (p=0.029) were increased in the study group. Conclusion: The clinical parameters of the BOP index and PD were significantly amplified in the MS patients. However, no causal relationship between the investigated inflammatory mediators and the clinical findings could be established in this case series. The study was registered in the German clinical trial registry (DRKS00022956,registered 28/08/2020).

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The Matrix Metalloproteinases Panel in Multiple Sclerosis Patients Treated with Natalizumab: A Possible Answer to Natalizumab Non- Responders

Abstract: 1. The serum level of MMP9 significantly decreased by NAT treatment and correlates with MS activity; 2. After eight months of NAT treatment, the MMPs signature and the MMP9/MMP2 ratio decreased; 3. MMP9 might be used as a biomarker in MS patients treated with NAT.

Cited by 14 publications

References 0 publications

Expression of Inflammatory Mediators in Biofilm Samples and Clinical Association in Multiple Sclerosis Patients in Remission—A Pilot Study

Expression of Inflammatory Mediators in Biofilm Samples and Clinical Association in Multiple Sclerosis Patients in Remission—A Pilot Study

CSF biomarkers in multiple sclerosis: beyond neuroinflammation

Expression of inflammatory mediators in biofilm samples and clinical association in multiple sclerosis patients in remission – a pilot study of case series

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