Author Topic: Tysabri & JC virus infection  (Read 191 times)

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Offline agate

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Tysabri & JC virus infection
« on: March 25, 2014, 10:30:44 am »
From Medical News Today, March 24, 2014:

Quote
Natalizumab treatment in patients with multiple sclerosis 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 natalizumab 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 healthy volunteers (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.

"We detected JCV DNA within the cell compartments of natalizumab-treated MS patients after treatment inception and after 24 months. The JCV DNA may harbor [live] in CD34+ cells in bone marrow that mobilize into the peripheral circulation at high concentrations. Cells with latent infection initiate differentiation to CD19+ cells that favor growth of JCV. Continued studies are needed to further investigate natalizumab treatments as the mechanism of PML."



References

JAMA Neurol. Published online March 24, 2014. doi:10.1001/.jamaneurol.2014.63.

The authors made conflict of interest disclosures. The study was supported by the Division of Intramural Research funds (National Institute of Neurological and Communicative Diseases and National Institute of Allergy and Infectious Disease laboratories) and other sources. ...

Article adapted by Medical News Today from original press release.




 

The article can be seen here.
MS Speaks--online for 17 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.

Offline agate

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Re: Tysabri & JC virus infection
« Reply #1 on: March 30, 2014, 02:21:37 pm »
More on this study appeared in DailyRx News, March 29, 2014:

Quote
Increased JC virus infection seen in MS patients taking natalizumab

 Author: Sheryl Wood / Reviewed by: Robert Carlson, M.D Beth Bolt, RPh


Natalizumab is often used to fight the symptoms and progression of multiple sclerosis, but the drug comes with a significant risk of a rare and potentially fatal viral infection.

Multiple sclerosis patients who take natalizumab (brand name Tysabri) have about three times the rate of progressive multifocal leukoencephalopathy (PML) — a rare and usually fatal disease of the brain. While it is known that PML is caused by the JC virus, it isn’t clear why more MS patients taking natalizumab get PML.

A recent study found that the JC virus may live and grow in certain cells of the immune system and that natalizumab may enhance this process.

"Ask your doctor about your MS treatment options."
Elliot M. Frohman, MD, PhD from the Department of Neurology at the University of Texas Medical Center in Dallas, TX led the research team.

The study involved three groups of people. Twenty-six multiple sclerosis (MS) patients had their blood drawn before starting natalizumab and regularly over the next 10 monthly treatments. Another group of 23 patients had their blood drawn once after they had completed at least 24 treatments with natalizumab. Blood was also collected for a third group of 18 people without MS who served as the control group for the study.

The research team measured the amount of JC virus in the blood of the study participants. They looked at different types of white cells in the patients, called CD34 and CD19 cells, to see which cells the virus was found in.

JC virus was found in either the CD34 or CD19 white cells of people in all three groups. The virus was found in cells of 50 percent of the patients starting natalizumab treatment, 44 percent of the patients who had more than 24 treatments, and in 17 percent of the normal control group.

Results of the research showed that the percentages of CD34 and CD19 cells were higher in the blood of MS patients treated with natalizumab, compared to people in the healthy control group. This increase started after three months of treatment.

The authors theorized that the JC virus might have lived in CD34 cells in the bone marrow and that natalizumab moved these cells into the bloodstream. They also suggested that the cells infected with JC virus might become CD19 cells where the virus could then grow.

“Continued studies are needed to further investigate natalizumab treatments as the mechanism of PML,” the authors concluded.

The research was published in the March issue of JAMA Neurology.

Funding for the study was provided by the National Institute of Neurological and Communicative Diseases and the National Institute of Allergy and Infectious Disease, as well as a grant from the National Multiple Sclerosis Society.

Dr. Frohman disclosed receiving fees for speaking and consulting from Biogen Idec, makers of natalizumab.

The article can be seen here.
MS Speaks--online for 17 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.

Offline agate

  • Administrator
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MS Speaks--online for 17 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.

Offline agate

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Re: Tysabri & JC virus infection
« Reply #3 on: June 03, 2014, 10:54:35 am »
An editorial in the Multiple Sclerosis Journal, June 2, 2014, gives a very understandable summary  of the situation with respect to JC virus testing and PML.  If this link doesn't work for people, I hope someone will let me know.

MS Speaks--online for 17 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.