MS Relapses During Natalizumab Therapy Traced to Drug’s Greater Impact on Regulatory T-cells

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Natalizumab and MS

Natalizumab (Tysabri) harnesses multiple sclerosis (MS) activity by targeting CD49, a molecule on the surface of immune cells. Now, researchers found that the drug reduces the factor on regulatory T-cells to a greater extent than on inflammatory T-cells — a mechanism that might explain disease exacerbation during treatment.

The molecule under investigation in the study, CD49, is the main factor governing migration of immune cells to the central nervous system. By blocking its actions, natalizumab is highly effective in inducing MS remission. Some patients, however, experience relapses and disease progression while under treatment.

Natalizumab treatment does not necessarily block all CD49; earlier studies have shown that the antibody is able to bind between 60 percent and 100 percent of all available molecules. Scientists also do not understand how effective natalizumab treatment is in reducing CD49 on different types of immune T-cells.

Researchers at the National Center of Neurology and Psychiatry in Tokyo, Japan, therefore, measured the molecule on inflammatory and regulatory T-cells, to explore if potential differences could explain why the treatment is not optimally suppressing disease activity in some patients.

The study, Disrupted balance of T cells under natalizumab treatment in multiple sclerosis, analyzed the expression of CD49 in 27 patients who had never received the drug, eight natalizumab-treated MS patients, and eight healthy controls. Also, seven patients with neuromyelitis optica (NMO) or NMO spectrum disorder, a condition where the optic nerve is affected by inflammation and demyelination, were included.

Results, published in the journal Neuroimmunology and Neuroinflammation, showed that natalizumab treatment reduced CD49 on regulatory T-cells — so called Tregs — more than on inflammatory T-cells. During the study, two patients suffered a disease exacerbation, and the team observed that the number of inflammatory cells still expressing CD49 was remarkably high compared to the number of CD49-expressing Tregs.

Researchers also noted that the remaining CD49-positive cells expressed more pro-inflammatory, and less regulatory, factors, suggesting that the pool of CD49-immune cells not eliminated during natalizumab treatment might contribute to disease exacerbations.

Study results further imply that the ratio of CD49 on inflammatory to regulatory cells could be used as biomarkers to improve monitoring of patients on natalizumab treatment.

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  1. Spiro says:

    Another worthless drug that has shown to do nothing in slowing down progression. All these immune modulators have been shown to do nothing but reduce relapses which are not correlated with disability progression. There is only one solution until a cause is found: reboot immune system with HSCT for RRMS less than ten years since diagnosis. Any later disability becomes permanent. Progressive patients need different solutions: eliminating immune cells trapped behind CNS. And stem cells. There needs to be a new paradigm shift in how MS is treated

      • Spiro says:

        I’d rather be a jack ass than uneducated, pal. I was on tysabri for much longer than you and progressed . I did HSCT , if you even know what that means, and rebooted my immune system. Come talk to me after you reach SPMS, mr smug

        • MP says:

          Spiro – Your tone is condescending. No reason for that. My ex-wife has been on Tysabri for many years and had had excellent results, with her progression largely held in check. I would say it is almost a miracle FOR HER. Clearly mileage may vary and it would seem you did not have good results when you were taking the drug. But there’s no need to dismiss someone else’s experience and make disparaging comments toward them (name calling – “uneducated” “Pal” “Mr. Smug”). I’m glad you were able to reboot your immune system. Perhaps providing more information on your experience, without demonizing others or other treatment options, would be a more helpful approach and would spark a meaningful dialog.
          All the best, my friend.

          • spiro says:

            My reply was for TK above, but since you decided to chime in, perhaps you can understand why when someone calls me a jack ass (disparaging remark? No?) who doesn’t know me or my experience, they better know what they’re talking about. And instead of inquiring about more information (my post was not meant to stop anyone from taking Tysabri, quite the contrary:to help people make intelligent decisions that will better their health), I get raked over the coals for trying to say the right thing. I only wish I had the same information ten years ago. So, for the record, here is my experience. You can take it with a grain of salt or continue down the Biogen lifetime merry-go-round. My facts are supported by peer-reviewed literature and studies. Fact: Tysabri only slows disability progression by 40% (Biogen’s own studies); fact, Tysabri reduces MRI indicators of inflammation by 90% (impressive, until you realize that there is NO correlation between MRI inflammation and disability progression); fact, Tysabri was recently shown to have NO effect on SPMS; fact, Tysabri has contributed to thousands of worldwide MS deaths due to PML, almost 1/3rd of which patients die and the other 2/3rds live with severe disability. So, go tell the families that have suffered about this “miracle” drug. I’m glad it’s working for your wife. But if it were my wife, I would want the gold standard for RRMS: HSCT. Read up on the studies with progression free survival to 15 years, a record Tysabri can’t even hope to achieve. Furthermore, if you’re so inclined to know about the pathophysiology of MS, b cells are implicated more than T cells (as subset of autoimmune cells that Tysabri doesn’t address). So instead of blanket making your own disparaging remarks against a post that wasn’t even addressed to you, it would perhaps behoove you to re-read the first post above by TK. I encourage you to join the HSCT forum for more information. Peace out and best of luck to you

          • Chandler Hovey says:

            Spiro and TK
            My first symptoms appeared at age 36, disappeared and were found clinically evident at age 56 when MRIs showed lesions after 20 years of no MTI lesions. went thru treatments with Avonex, double Avonex, REBIF, and 1 yr of Tysabri all with no discernible slowing disease progression. Now at age 75 taking nothing I’m just trying to deny the inevitable. Not inspiring what our FDA/Pharmacy industry have come up with. In fact , almost fraudulent or criminal. Don’t be too hopeful about Tysabri, there’s still way too much promise hoped for from FDA/Pharma’s approach/process/methodology. A sea change in approach is needed to eradicate this mysterious disease. Chasing after remedies that show “statistically significant” improvements has so far only shown verifiable results in Pharma’s consistently reliable long term earning’s growth.

  2. Cassie says:

    I have been on Tysabri for 7 and a 1/2 years and have had no relapses or progression. I am also a mother of 2 young children (one with special needs), work, play sport and fully function and have never been better in my 13 years of being diagnosed. Not a worthless drug for me at all ☺️

    • Spiro says:

      Hi Cassie and thanks for posting your experience. Like I said, for me, and many others, Tysabri will eventually lead to progression. Does it slow it? Yes, of course. Does it stop it like HScT? No. That is all I wanted to share. Virtually all cases of MS eventually will progress. There is unfortunately, as we all know, no cure. But the closest we have that should become the standard of care, instead of a lifetime of immune suppression, is HSCT. I am very happy it has worked for you.

      • Dani says:

        that’s great to hear! I am scheduled for HSCT this summer, and I can’t wait! I tried just about every drug to no avail, and I am thankful to have been pointed in the HSCT direction!

  3. Maureen says:

    For me, Tysabri has made a huge difference. I was diagnosed in 2013, so haven’t been on it that long and it is my first (and hopefully only) drug. I’m monitored quite well for I’m in a clinical trial. The only drawback for me is a “wear-off effect”. I basically hobble into the infusion chair and dance out. By week 4 (and I’m beginning to feel it today), stiffness is ever present and I’m most uncomfortable. I just push through it until it’s time for my next infusion (8 days away). I chose this for I didn’t want daily injections or the other meds that I had read about. My Neurologist didn’t push me; he allowed me to make my own choice. The spectre of PML looms, but as I said, I’m monitored closely and as soon as the JCV virus rears it’s ugly head, I’m done. Best of luck to all warriors who fight this battle. We need to support each other for there is truly strength in numbers (and misery loves company)! Now to research and discuss HSCT with my doctor next week!

    • Spiro says:

      Thanks for your level-headed response, Maureen. I obviously used the wrong word “worthless” when starting the post and got attacked by TK above when clearly that has been my experience. If you want more information about HSCT, join the main FB forum or Florence forum where I am an admin. Best of luck

  4. Yoni says:

    Hi guys I am a 25 year old male. I was diagnosed in 2012.but had symptoms since 2010. I started on rebif.After a year on rebif my neuro said I was progressing on it and wanted me to start tysabri I said no. I was in denial. Then on August 31 2014 I woke up with no eye sight in my left eye. That scared the hell out if me. I already had 3 previous relapses that debilitated me. I called my neuro and started tysabri immediately. I been fine so far and always think about pml. I just pray everything works out. God bless us all.

  5. sandra kersey says:

    I’ve had MS for 23 yrs & tried every drug on offer,got to hate injection’s after trying,”Beta interferon” I was diagnosised aged 34,& on trails for Tysabri,& was so well & back to work,then relapsed again waiting for tysabri to go through NICE,i’ve been on it now for over 7 yrs & had no relapse’s,so i can only speak for myself,& feel it has helped me,for how much longer,who know’s,but what else is their ? All in my monthly group are doing well,5 of us,3 have now the JC,but not developed the JC virus & still doing as well as doesn’t suit everyone i agree,but its every individual’s choice & we have a great neurologist & MS nurse that will see us at anytime to help,talk & advise & are like friends to us all,no pressure to do anything we don’t wont to do or try..we have MS but so far it hasn’t got us !! Please all stay positive when u can,& support each other when possible.It’s a shit ( excuse that word) illness !! Good luck to all u other MS sufferer’s x

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