JC VIRUS TEST - HOW DO YOU GET IT?

A board to discuss the newly-released drug Tysabri, (formerly known as Antegren) as a treatment for Multiple Sclerosis

JC VIRUS TEST - HOW DO YOU GET IT?

Postby yonderboy » Tue Oct 27, 2009 1:55 pm

From Forbes.com

Reviving Tysabri

Matthew Herper, 10.27.09, 03:59 PM EDT

The drug's inventor believes a new test might identify people who are less at risk for a deadly side effect.

Worries about a potentially deadly side effect have long impeded sales of the multiple sclerosis drug Tysabri, made by Elan. But now the medicine's inventor says he has created a diagnostic test that might reveal those patients who are less at risk of the side effect. That could increase the market for the drug, which is already a $1 billion seller.

Ted Yednock, a researcher at the South San Francisco labs of Elan ( ELN - news - people ), invented the antibody that would become Tysabri in 1992. It offered a new way of curtailing the immune system, which goes haywire in MS and the gastrointestinal ailment Crohn's disease. The drug was approved to treat MS in November 2004.

But only three months after that approval, Tysabri was withdrawn. The immune suppression caused by the drug was allowing a usually dormant virus to infect patients' brains, causing a brain-destroying condition called progressive multifocal leukoencephalopathy (PML). Estimating that the virus occurred in one in 1,000 treated patients, the Food and Drug Administration allowed Tysabri to re-enter the U.S. market in July 2006.

Ever since, Yednock, 52, has been on a quest to understand the virus that causes PML. When Tysabri was pulled, researchers thought that most--90% or more--of human beings were infected with the virus that leads to PML (named JC, after the first two patients to get PML). Yednock says that work done by his team shows that only 50% of patients are infected with the JC virus, meaning that there are many patients for whom Tysabri might bear little PML risk at all.

Even with the specter of PML, 60,900 patients have chosen to take Tysabri, which is given by infusion and is very effective at preventing the brain lesions caused by MS.

Yednock's quest is taking on more urgency, as worries about PML continue to build. The risk of PML rises as patients get more infusions of Tysabri, and as time passes more PML cases are a certainty. On its most recent conference call, executives at Biogen Idec ( BIIB - news - people ), Elan's partner on the drug, said that the FDA might want to add discussion of this increase to the product's label.


On Oct. 23, European regulators said that 23 cases of PML had been reported, far more than investors had expected. Wall Street analysts who cover Biogen for Bernstein, Deutsche Bank and Oppenheimer all said this could mean the risk of PML had doubled. The FDA-approved labeling for Tysabri puts the risk of PML at 1 in 1,000. With the new cases included, it could be 1 in 400, according to the analyst reports. Most analysts are skeptical that Elan and Biogen-Idec can reach their stated goal of getting 100,000 people on the drug.

Yednock says that the problem with PML testing up until now has been that the JC virus looks a lot like an evolutionary cousin, the BK virus. Antibody tests developed for JC virus were also set off by the BK virus, but BK virus doesn't cause the PML brain infection.

For some patients with JC virus, the virus is excreted in urine. By collecting blood samples from those people, Yednock had a group of patients he knew were infected with JC, allowing him to start developing a test that captured them all.

The test Yednock and his colleagues developed found that something like 50% of the patients have JC virus. There are eight cases of patients who developed PML where Elan and Biogen-Idec have blood samples going back long before the infection happened. All of those cases had JC virus antibodies in their bloodstreams a year before they got PML. "That's a pretty good starting point," says Yednock.

Elan has transferred the assay to a commercial laboratory, a step toward making it available to patients. The test, which uses antibodies to detect the presence of JC virus, could be done with just a saliva sample. It has not been evaluated by regulators or the larger scientific community, but the hope is that doctors might be able to use it to pick which patients are the best candidates for Tysabri therapy


I'm sure that after the events of the last week, that all Tysabri users are already thinking about it (I had infusion #27 last week), but is it possible to get a JC Virus test today? I'm in Toronto, and the sad fact is that any JC Virus testing that they've done up here (mainly CSF taps for PML concerns) are sent to the States. Through google - I've found a lab in Missouri (Viracor) that appears to do a pretty sophisticated PCR test for the JC Virus on whatever sample you give them (blood, urine, CSF) - the challenge for me, is how do I get the sample to them?

The article above is long on hope, but short on details - does anybody have any more info. on this test that Yednock has developed, or when it will become available?

Thanks,
John
User avatar
yonderboy
Family Member
 
Posts: 25
Joined: Wed Jan 14, 2009 4:00 pm

Postby prof8 » Tue Oct 27, 2009 10:47 pm

That is a great question. I wish I could answer it. Yednock's test is now apparently in a commercial laboratory for processing (?) but who knows what that means. My suggestion is for all of us to call our neurologists and ask about the specifics.

I'm not sure if the PCR test at Viracor is the same thing. My neuro tests my blood every 3 months and sends it to the Mayo Clinic--some of the PML patients did show in the blood eventually but not always soon enough to catch it. But my clinic thinks its worth it to test. However, I think the test I get might be the PCR test which looks for pieces of JC virus DNA in the blood. Yednock's test sounds like an antibody test which is different.
User avatar
prof8
Family Elder
 
Posts: 189
Joined: Sun Jul 13, 2008 3:00 pm

Postby singerdf » Tue Dec 01, 2009 6:01 pm

John,

I have read all of those articles as well. You sum up the information very well. I am on infusion #30 on Monday and worry everyday about developing PML with every infusion. I have asked my neurologist repeatedly about being tested for the JC Virus. His response has always been that when there is a valid test with results that are meaningful he will have all of his patients tested.

So, I wait and worry.

Debbie :lol:
User avatar
singerdf
Newbie
 
Posts: 7
Joined: Mon Nov 30, 2009 4:00 pm
Location: Detroit, MI

Re: JC Virus Test - How do you get it?

Postby NHE » Wed Dec 02, 2009 12:41 am

singerdf wrote:I have asked my neurologist repeatedly about being tested for the JC Virus. His response has always been that when there is a valid test with results that are meaningful he will have all of his patients tested.


Last May I went to a Biogen sponsored talk where the main subject was Tysabri. The main speaker was a neurologist that had MS and was also taking Tysabri. He had this to say about treating and testing paitients...

There’s a danger of PML if the CD4 count gets below 400.
Touch program, and/or Dr. Macaluso, monitors CD4 count.
Patient is off of Tysabri if CD4 count is less than 500.
If PML is determined, treatment is plasma exchange 5x over a 10 day period. Steroids are given 10 days after plasma exchange in order to prevent massive brain inflammation from the immune system’s attack on the PML virus (immune system rebound inflammation aka IRIS, actually Immune Reconstitution Inflammatory Syndrome).


Note that this isn't a direct test for the JC Virus, but it does offer a means of patient monitoring.

NHE
User avatar
NHE
Volunteer Moderator
 
Posts: 3300
Joined: Sat Nov 20, 2004 4:00 pm

Postby singerdf » Wed Dec 02, 2009 6:06 am

Looks like I will be asking again about my CD4 counts. I just had a panel run for Vitamin D in particular and wonder whether my doctor included a full cell count panel.

The recommendation seems reasonable to me.

Thanks for the information,

Debbie
User avatar
singerdf
Newbie
 
Posts: 7
Joined: Mon Nov 30, 2009 4:00 pm
Location: Detroit, MI

Postby singerdf » Wed Dec 02, 2009 6:21 am

You now have me thinking: if my CD4 count fell below 400, I would assume I would be sick in other ways??? If TOUCH is supposed to be monitoring this why can't I find it on any of my blood work? Also I am not routinely testing my blood only answering the questions before I start, BP and temp and making sure I am not pregnant.

There still seems to be some confusion about the JC Viral load and where the virus is found.

Looks like there is still much work to be done about understanding this nasty side effect.

Debbie
User avatar
singerdf
Newbie
 
Posts: 7
Joined: Mon Nov 30, 2009 4:00 pm
Location: Detroit, MI

Re: JC Virus Test - How do you get it?

Postby NHE » Thu Dec 03, 2009 1:35 am

singerdf wrote:If TOUCH is supposed to be monitoring this why can't I find it on any of my blood work?


That's a good question. I can only tell you what the doctor said during his presentation. His full name is Vincent Macaluso. He runs a clinic on the East Coast, http://www.macalusomedical.com/VFP.html, and also wrote a book, "MS From Both Sides of the Desk." If there's a discrepency between what he said about the TOUCH program and what Biogen has to say about it, then you might want to contact him.

NHE
User avatar
NHE
Volunteer Moderator
 
Posts: 3300
Joined: Sat Nov 20, 2004 4:00 pm

Postby singerdf » Thu Dec 03, 2009 5:55 am

Thank you.
User avatar
singerdf
Newbie
 
Posts: 7
Joined: Mon Nov 30, 2009 4:00 pm
Location: Detroit, MI

Postby chalam » Thu Dec 03, 2009 12:46 pm

What is CD4? Is it in the blood? The TOUCH program does not monitor this as far as I know.The TOUCH protocol does not require blood work.
It simply keeps track of who is infused where. The TOUCH protocol requires the infusion centers to ask 3 questions of the patient at every infusion; these answers are then forwarded to the TOUCH folks. My daughter is on her 7th infusion, from 3 different centers. She has only been asked these questions one time, yet her "answers" from every month are on file with TOUCH!
User avatar
chalam
Getting to Know You...
 
Posts: 14
Joined: Wed Apr 20, 2005 3:00 pm
Location: Tokyo, Japan

Postby jr5646 » Fri Dec 04, 2009 1:06 am

How ironic... I just had an appointment with my neuro today and I'm looking over my bloodwork order.. I'm in the US, so I don't know if this will apply to CA, but I'll list verbatum just in case. We also discussed the risk of PML briefly, and he said that we just have to be monitored more closly. I've been on TY since Oct. 2007. He took me off after 26 infusions (two years) and I slid downhill quickly (rebound effect??) - after being off for approx. 6 months he put me back on. So I've had about 32 infusions - Not doing too well now either, but the first two years felt great, still had some managable deficits, but didn't seem to be progressing either..

The interesting part, is that they (multiple neuro facility) are starting this new stratagy with long term (over two years) TY patients to spread out the time in between infusions to try to minimize the risk of PML... instead of every 4 weeks, it will be every 5 weeks for maybe the next three or four infusions, then every 6 weeks thereafter. This is the first time I've heard of this being done??

The scary part, is that he mentioned malignancies with TY?? I did a double take - Can they be detected in bloodwork, I said? not easily was his reply.. I was kinda speechless at that point.. again, this is the first I've heard of this one.. I'm researching it now.

Anyway the Bloodwork Ordered:

JC POLYOMA VIRUS DNA, QL [JCPVQ]

HEPATIC FUNCTION PANEL [HFPA]

LYMPHOCYTE SUBSET PANEL 1 [8823005]

BASIC METABOLIC PANEL [8004900]
jr5646
Family Elder
 
Posts: 185
Joined: Thu Nov 26, 2009 4:00 pm

Re: JC Virus Test - How do you get it?

Postby NHE » Fri Dec 04, 2009 4:47 am

This is really odd. I just read through the doctor's prescribing information for Tysabri and it makes no mention of low CD4 counts. In fact, the only thing it says about blood cell counts is this...
Laboratory Test Abnormalities
TYSABRI induces increases in circulating lymphocytes, monocytes, eosinophils, basophils, and nucleated red blood cells. Observed changes persist during TYSABRI exposure, but are reversible, returning to baseline levels usually within 16 weeks after the last dose. Elevations of neutrophils are not observed. TYSABRI induces mild decreases in hemoglobin levels that are frequently transient.

The Biogen reps were in the room at the presentation. They supposedly approved everything he had to say about Tysabri. If I go to another one of their sponsored talks, then I will take the opportunity to ask them about CD4 counts.

NHE
User avatar
NHE
Volunteer Moderator
 
Posts: 3300
Joined: Sat Nov 20, 2004 4:00 pm

Re: JC Virus test - How do you get it?

Postby NHE » Fri Dec 04, 2009 5:03 am

OK, this is what I was able to find from a clinical diagnostic lab company's page on lymphocyte subest panel 1.
Lymphocyte Subset Panel 1 7197X

Includes: Absolute Lymphocytes, Absolute CD3, Percentage CD3, Absolute CD4, Percentage CD4, Absolute CD8, Percentage CD8, CD4/CD8 Ratio (calculated), Absolute CD16/56, Percentage CD16/56, Absolute CD19, Percentage CD19


So it looks like they are testing CD4 counts. Anyways, from the info jr5646 posted, they are also testing blood samples for JC virus DNA.

NHE
User avatar
NHE
Volunteer Moderator
 
Posts: 3300
Joined: Sat Nov 20, 2004 4:00 pm

Postby singerdf » Fri Dec 04, 2009 5:08 am

My neurologist has talked about similar change in timing of infusions. The problem is there is no data to suggest what would come of stretching the time between infusions. I don't know about you, but my body starts to feel different about 5 days before I am scheduled for the next infusion. We have women asking if they can come every two weeks. So spreading the infusions out would be hard on many. As for the blood work, I have been asking about the JC Virus test for a while. The response I got: there are many ways to test for the virus and to date, we don't know where to look that would be the most indicative of PML onset: urine, plasma, PBMC or CSV. So I have not been tested. The lymphocyte subset should be interesting. Although, I made the point earlier in this topic. If your CD4+ count is low you would have many other health problems.

As more of us are on the medication longer, I think Biogen Idec needs to begin studies that address our subset of people. Furthermore, we are a group that has long been off any other therapy and follows the guidelines for non use of steroids seriously. I worry every infusion about what may come. It is also frightening to think that individual neurologists are making changes according to non existent guidelines.

On the last note: I have not read anything in the literature on malignancies. Time to look further.

Debbie
User avatar
singerdf
Newbie
 
Posts: 7
Joined: Mon Nov 30, 2009 4:00 pm
Location: Detroit, MI

Postby jr5646 » Fri Dec 04, 2009 9:21 am

singerdf wrote:My neurologist has talked about similar change in timing of infusions. The problem is there is no data to suggest what would come of stretching the time between infusions. I don't know about you, but my body starts to feel different about 5 days before I am scheduled for the next infusion.


I too felt subtle changes getting closer to the 4 week point, but that has but dissappeared since I was taken off for 6 months.. Even now that I'm back on, I'm slooooooooooly going down hill.

The strategy may work better if one doesn't go off the drug abruptly.. I think is the theory..

They don't have any data when you stop taking the stuff either? sux
jr5646
Family Elder
 
Posts: 185
Joined: Thu Nov 26, 2009 4:00 pm

Postby Rainbolt » Sat Jan 23, 2010 6:33 pm

I was told early on when PML was first reported and Tysabri was yanked that most human beings have the JC virus. So I don't get how testing positive for the virus alone causes people to be dxed with PML? I know JC virus turns into PML so is ita counter of the JC Virus and if it's a certain percentage it means it's graduated to PML??? *CONFUZZLED*
User avatar
Rainbolt
Family Member
 
Posts: 33
Joined: Thu Nov 19, 2009 4:00 pm

Next

Return to Tysabri (Antegren or Natalizumab)

 


  • Related topics
    Replies
    Views
    Last post

Who is online

Users browsing this forum: No registered users


Contact us | Terms of Service