Natalizumab treatment in patients with MS associated with JC virus infection

Treatment with natalizumab in patients with multiple sclerosis (MS) appears linked with JC virus (JCV) infection, which can lead to a rare and often fatal demyelinating disease of the central nervous system called progressive multifocal leukoencephalopathy (PML) that destroys the myelin that protects nerve cells. The movement of cells with JC virus into the blood stream may provide researchers with a possible reason why patients with MS develop PML

Since was reintroduced as a biologic therapy for MS in 2006, more than 440 cases of PML have been reported. Risk factors associated with development of PML include receiving 24 or more natalizumab infusions, receiving other immunosuppressive treatments and testing positive for JCV antibodies in a blood test.

The authors evaluated 49 patients with MS and 18 healthy volunteers by drawing blood samples and examining CD34+ cells from the bone marrow plus CD19+ and CD3+ cells. Among the 49 MS patients, 26 were beginning natalizumab therapy. For these patients, blood was drawn at baseline and again at approximately three-month intervals to 10 months.. Blood also was drawn on a single occasion from 23 patients with MS receiving natalizumab for more than two years and from the 18 healthy volunteers.

Of the 26 patients beginning natalizumab therapy, 50 percent had detectable JC virus DNA in at least one cell subtype at one or more measures. Among the 23 patients who received natalizumab treatment for two years, 10 patients (44 percent) had detectable viral DNA in one or more cell subtype, as did three of the 18 (17 percent). Of the 49 total patients with MS, 15 (31 percent) were confirmed to have JCV in CD34+ cells and 12 of the 49 (24 percent) had it in CD19+ cells.

Authors of the paper Elliot M Frohman, M.D., Ph.D., of the University of Texas Southwestern Medical Center, Dallas, and colleagues wrote: "We detected JCV DNA within the cell compartments of natalizumab-treated MS after treatment inception and after 24 months. The JCV DNA may harbor [live] in CD34+ cells in that mobilize into the peripheral circulation at high concentrations. Cells with latent infection initiate differentiation to CD19+ that favor growth of JCV. Continued studies are needed to further investigate natalizumab treatments as the mechanism of PML."

More information: JAMA Neurol. Published online March 24, 2014. DOI: 10.1001/.jamaneurol.2014.63

add to favorites email to friend print save as pdf

Related Stories

FDA investigating PML in patient taking MS drug

Aug 31, 2013

(HealthDay)—The U.S. Food and Drug Administration is investigating the possible association between a rare brain infection and the multiple sclerosis (MS) drug Gilenya (fingolimod), according to a drug ...

Recommended for you

Celebrities in 'Ice Bucket Challenge' to fight disease

8 hours ago

Steven Spielberg, Justin Bieber and Bill Gates are among many celebrities pouring buckets of ice water over their heads and donating to fight Lou Gehrig's disease, in a fundraising effort that has gone viral.

Study helps explain why elderly have trouble sleeping

9 hours ago

As people grow older, they often have difficulty falling asleep and staying asleep, and tend to awaken too early in the morning. In individuals with Alzheimer's disease, this common and troubling symptom ...

Targeted brain training may help you multitask better

10 hours ago

The area of the brain involved in multitasking and ways to train it have been identified by a research team at the IUGM Institut universitaire de gériatrie de Montréal and the University of Montreal.

User comments