Tysabri (natalizumab)

A protein called MMP-9 could be a predictive marker of progressive multifocal leukoencephalopathy development in patients with relapsing-remitting multiple sclerosis (RRMS) who are being treated with Tysabri (natalizumab), a study suggests. The study, “Dynamic changes of MMP-9 plasma levels correlate with JCV reactivation and immune activation in natalizumab-treated multiple sclerosis patients,” was published in the journal Nature Scientific Reports. Brain inflammation in multiple sclerosis patients occurs when immune cells breach the blood-brain barrier. This layer of cells protect the brain and its supporting fluids, such as cerebral spinal fluid (CSF), from dangerous agents circulating in blood. How easily immune cells can break through the blood-brain barrier depends on its porousness. For instance, it is known that decreasing the activity of matrix metalloproteinases (MMP) increases the protective layer’s permeability. Matrix metalloproteinases are a family of proteins responsible for the degradation of collagen and other proteins in the extracellular matrix, which provides structural and biochemical support to surrounding cells. One metalloproteinase, called MMP-9, has been extensively studied in multiple sclerosis. MMP-9 levels are elevated in the CSF of multiple sclerosis patients and considered a potential biomarker of disease activity and possible therapeutic target. Tysabri (marketed by Biogen) is one of the most effective treatments for RRMS currently available. It works by blocking the entry of immune cells into the brain. Tysabri is known to decrease MMP-9 levels in the CSF and serum in RRMS patients. However, Tysabri has been associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML). This rare and often fatal viral disease, caused by the John Cunningham virus (JCV), is characterized by progressive damage and/or inflammation at multiple sites in the brain. The reduced migration of immune cells across the blood-brain barrier induced by Tysabri is thought to be the cause of this increased PML risk. Whether MMP-9 is involved in this process has not been studied. To look at this, a team led by researchers from Sapienza University and Aldo Moro University in Italy investigated MMP plasma levels following Tysabri treatment in the context of JCV. The team specifically looked at how levels of MMP-9 were linked to disease-related processes. Samples from 34 RRMS patients being treated with Tysabri (intravenous dose of 300 mg every four weeks) were analyzed. As expected, results showed that MMP-9 plasma levels stabilized within one year of Tysabri treatment (up to 12 Tysabri infusions), although they began to steadily rise afterward (between 12 and 24 infusions). These increased MMP-9 plasma levels were not associated with clinical relapses in RRMS patients. "MMP-9 levels increased in plasma accordingly with [Tysabri] infusion number," the researchers wrote. In comparing JCV-positive and JCV-negative samples, the researchers observed an increase in MMP-9 plasma levels in JCV-positive samples. This result suggested that JCV circulation in peripheral blood could be implicated in the increase of MMP-9 levels. Interestingly, increased MMP-9 plasma levels were found to be correlated with immune cell activation. "Our findings suggest a potential pathogenic role of MMP-9 in the development of progressive multifocal leukoencephalopathy during [Tysabri] treatment, and its possible use as a marker of JCV reactivation,” the researchers wrote. Future studies are nonetheless needed to confirm these findings in larger groups of RRMS patients.

Herbicide Called Linuron Seen to Trigger Inflammatory Signals Linked to MS in Study This is only a mouse study, but this herbicide has been banned in Europe because of health concerns. Its effects seem worthy of further investigation. The herbicide linuron, commonly used with other herbicides, insecticides,…

Initial treatment of relapsing-remitting multiple sclerosis (RRMS) with Gilenya (fingolimod), Tysabri (natalizumab), or Lemtrada (alemtuzumab) is associated with a lower risk of conversion to secondary progressive multiple sclerosis (SPMS), compared with interferon beta or Copaxone (glatiramer acetate), a study reports. Findings also showed that…

WeHealth, PathMaker Collaborating to Develop MyoRegulator as Noninvasive Treatment for Spasticity I’m one of the many people with multiple sclerosis (MS) for whom spasticity is a significant problem. This is a nonmedicinal approach to dealing with it. I hope it doesn’t take too long to make this…

Biogen announced the start of a global Phase 3b clinical trial to evaluate the efficacy and safety of extended interval dosing (EID) with Tysabri (natalizumab) in patients with relapsing-remitting multiple sclerosis (RRMS). Results of the six-week dosing interval will be compared with the approved standard interval dosing…

Many years ago a woman I know who has multiple sclerosis (MS) became pregnant. After her child was born her MS became significantly worse. There have been many studies on the impact of pregnancy on someone with MS, with most concluding that the number of MS relapses are…

Clinical data and real-world results support the long-term efficacy of Biogen’s medications for multiple sclerosis (MS), according to scientific presentations being released by the company. Specifically, findings support the effectiveness of Tecfidera (dimethyl fumarate) and Tysabri (natalizumab) used early in the disease’s course, as well as the…

Four disease-modifying therapies (DMTs) for  multiple sclerosis — Avonex, Rebif, Betaferon, and Copaxone — are cost-effective and reduce disease progression in MS patients, especially those with relapsing-remitting disease, according to 10-year, real-world results from U.K.’s MS Risk Sharing Scheme (RSS). But the long-term benefits observed wane over…

Abreos Biosciences announced the U.S. launch of moNATor, a laboratory-developed test that can help physicians monitor the levels of Tysabri (natalizumab) in patients with multiple sclerosis (MS). Tysabri (approved for relapsing forms of MS, by Biogen) administered at a dose of 300 mg every four weeks is known to be…

Complications from Gilenya Treatment Managed Successfully, Case Report Says This wasn’t a minor complication. It was a version of PML, a brain disease that can be fatal. PML is also a known side effect of Tysabri, so the report of a successful treatment should be important to…

An approved lymphoma treatment, rituximab was found to be effective and safe for relapsing-remitting multiple sclerosis (RRMS) patients whose active disease has failed to respond to immunosuppressive therapies, a retrospective French study reports. Published in the Multiple Sclerosis Journal in an article titled, “Efficacy of…

#ACTRIMS2018 – Third Course of Lemtrada Improves Relapse, Disability in MS Patients, CARE-MS II Trial Shows The normal treatment regimen with Lemtrada is a series of two treatment courses, with the second infusion course given 12 months after the first. A “selling point” for this disease-modifying therapy (DMT) is…

One of the many disease-modifying therapies (DMTs) that I’ve been on over the many years of my treatment for MS is Tysabri (natalizumab). It worked well, holding the progression of my MS at bay for the several years that I received the infusions. I’d probably still be on it…

There’s been a lot of interest in the treatments (including natural treatments) for progressive MS that were presented at the ECTRIMS-ACTRIMS conference in Paris last week. Here are a few of our reports involving that research. #MSParis2017 – MedDay’s High-Dose Biotin, MD1003, Improves Disability in Progressive MS…

Long-term Tysabri (natalizumab) treatment of relapsing multiple sclerosis (RMS) improves physical and mental health and leads to greater satisfaction with therapy, new research shows. The study, ”Long-term natalizumab treatment is associated with sustained improvements in quality of life in patients with multiple sclerosis,” appeared in the journal…

The European Medicines Agency Pharmacovigilance Risk Assessment Committee (PRAC), responsible for assessing and monitoring safety issues for human medicines, completed a review on the risk for progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients treated with the medicine Tysabri (natalizumab). The issued guidelines have the objective of minimizing patients’ risk.