progressive multifocal leukoencephalopathy

In December 2019, I was stopped in my tracks, or rather wheels, as I was about to have my third infusion of Ocrevus (ocrelizumab), the multiple sclerosis disease-modifying therapy (DMT) that I’d been taking every six months for the past year. My neurologist had decided just a few…

No Link Between MS Severity, Vitamin D-related Mutations: Study Several studies over the years have indicated that there could be a link between a person’s vitamin D level and the risk of multiple sclerosis (MS). This study is slightly different. Researchers looked at whether genetic variations related to vitamin…

Deep Brain Stimulation May Help With MS-associated Tremors Deep brain stimulation (DBS) has been used to treat people with Parkinson’s disease and essential tremor, and in some cases, those with MS who have severe tremors, when other treatments have failed. The treatment involves implanting electrodes in the brain so…

One year of Ocrevus (ocrelizumab) treatment does not increase the risk for a rare brain infection — called progressive multifocal leukoencephalopathy (PML) — in people with multiple sclerosis (MS), a study suggests. The study, “Risk Assessment of Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis Patients during…

Mutations in the John Cunningham virus may serve as an early predictor for a rare brain infection in multiple sclerosis patients receiving Tysabri (natalizumab), a study suggests. However, more research is required to investigate the specific mutations in the viral VP1 gene, and validate the risk of the…

A 78-year-old man with multiple sclerosis (MS) developed the brain infection progressive multifocal leukoencephalopathy (PML) after two years of treatment with Ocrevus (ocrelizumab), a recent case report detailed. Treatment was discontinued and, as the patient’s symptoms worsened, he was moved to off-label…

The number of cases of Tysabri (natalizumab) that are associated with progressive multifocal leukoencephalopathy (PML) — a serious brain infection — in multiple sclerosis (MS) patients living in Sweden fell between 2006 and 2018, a study shows. Notably, the data highlighted that this drop was likely due to…

Switching to Ocrevus (ocrelizumab) within a relatively short period is a safe and effective option for people with relapsing-remitting multiple sclerosis (RRMS) who stop treatment with Tysabri (natalizumab), a small and retrospective analysis suggests. With a median washout period of six weeks between therapies, the 28 patients in this study…

Immune cells from patients with relapsing-remitting multiple sclerosis (RRMS) respond differently to Tecfidera (dimethyl fumarate) based on age, gender, and serum blood glucose levels, a study found.  The results suggest these patient-specific factors can modulate the response of immune cells, and should be…

Use of plasma exchange (PLEX) is not effective for treating progressive multifocal leukoencephalopathy (PML), a dangerous brain infection that has been associated with using the multiple sclerosis (MS) medicine Tysabri (natalizumab), a real-world study contends. The findings highlight the importance of  closely monitoring Tysabri users to detect…

Immune system activation induced by filgrastim may be beneficial for patients with progressive multifocal leukoencephalopathy associated with the use of Tysabri (natalizumab), without worsening multiple sclerosis (MS) progression, a study says. The study with that finding, “Treatment of natalizumab‐associated PML with filgrastim,” was published in…

New data suggests that treatment with Tysabri (natalizumab) in an extended interval dosing regimen is associated with a significantly lower risk of progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis (MS), compared with the standard interval dosing. The data was presented by Lana Zhovtis Ryerson, MD, on May 7 at the 2019 …

Progressive multifocal leukoencephalopathy, more commonly referred to as PML, is a brain infection that’s frequently fatal. PML is particularly dangerous to people with MS, which is why I’m interested in a report about a medication that’s showing promise as a PML treatment. The concern for people with MS is…

Nearly 18% of new multiple sclerosis (MS) patients referred to two speciality clinics in Los Angeles, California, had been misdiagnosed with the disease, according to a recent study. Most of them actually were affected by migraines, among other…

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.

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…

A case study reported the successful management of a multiple sclerosis (MS) patient who developed a rare condition in the brain — progressive multifocal leukoencephalopathy (PML) — due to treatment with Novartis Pharmaceutical’s Gilenya (fingolimod). The study, titled “Fingolimod-associated PML with mild IRIS in MS: A…

Extending the time between standard doses of Tysabri (natalizumab) from four weeks to up to 12 weeks is linked to a significant decrease in the risk of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients infected with what’s known as the JC virus, according to a recent analysis of data from…

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…

Editor’s note: Tamara Sellman continues her occasional series on the “MS alphabet” with this column referencing terms starting with the letter “P.” This post comes sixth in a series of seven. Symptoms of MS Progressive multifocal leukoencephalopathy (PML) Though progressive multifocal leukoencephalopathy (PML) isn’t an actual symptom of MS,…

Extending the dosing periods of Tysabri (natalizumab) treatment may help reduce the risk of progressive multifocal leukoencephalopathy, or PML, in multiple sclerosis (MS) patients infected with the JC virus, a study suggests. The study, “Natalizumab Extended Interval Dosing Is Associated with a Reduction in Progressive Multifocal Leukoencephalopathy…

A recent study has found Tysabri (natalizumab) treatment for two years to be efficient and safe in Japanese patients with relapsing-remitting multiple sclerosis (RRMS). The study, “Safety and Efficacy of Natalizumab in Japanese Patients with Relapsing-Remitting Multiple Sclerosis: Open-Label Extension Study of a Phase 2 Trial,” appeared in the journal…

Lemtrada (alemtuzumab) may be an effective option for relapsing-remitting multiple sclerosis (RRMS) patients withdrawing from prior treatment with Tysabri (natalizumab), an Italian study shows. The study, “High-Risk PML Patients Switching from Natalizumab to Alemtuzumab: an Observational Study,” appeared in the journal Neurology and Therapy. Tysabri, an antibody with…

A multiple sclerosis (MS) patient treated in Germany with Ocrevus (ocrelizumab) has developed the dreaded brain infection progressive multifocal leukoencephalopathy (PML). But it is not clear whether the recently approved Genentech/Roche-developed treatment is the cause. The patient took the last dose of a three-year course of Tysabri (natalizumab) in February. Tysabri is…

Many decisions to stop taking the multiple sclerosis treatment Tysabri (natalizumab) appear to be based largely on subjective factors such as patients’ or physicians’ view of the risk, rather than objective assessments of the risk, a study indicates. Tysabri is an approved immunotherapy for active relapsing-remitting multiple sclerosis (RRMS). Despite its benefits, there…

Progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients treated with Tysabri (natalizumab) is linked to better outcomes if the condition does not give rise to actual symptoms and is diagnosed early. Limited brain lesions and more protective immune responses were also seen in patients who fared better, but researchers…

Although Tysabri (natalizumab) is a highly effective in treating patients with relapsing-remitting multiple sclerosis (RRMS), some may develop progressive multifocal leukoencephalopathy (PML). According to a new study, this occurs because Tysabri impairs immune surveillance in the central nervous system and reactivates the latent John Cunningham polyomavirus (JCV). The study, “Natalizumab Affects…