MS Brain Lesions Linked to Early-life Viral Infection in Mice, Way of Blocking Inflammatory Spread Seen

MS Brain Lesions Linked to Early-life Viral Infection in Mice, Way of Blocking Inflammatory Spread Seen

An experimental treatment known as OB-002, that works to block an inflammatory molecule in the brain, prevented the development of lesions there after an early-in-life viral infection in a mouse model of multiple sclerosis (MS).

The research “Brain-resident memory T cells generated early in life predispose to autoimmune disease in mice,” was published in the journal Science Translation Medicine.

The association between viral infections in childhood and the risk of later developing autoimmune disorders such as MS is supported by epidemiological studies — studies of diseases in populations of people or animals. Still, the biological mechanism or process linking the two remains unknown.

A research team from Switzerland and Germany found that viral infection in the brains of mice early in life, but not at a later age, worsened those MS symptoms evident in a brain, like lesions, at sites where the virus had resided but was cleared. These changes were induced by immune T-cells containing the CD4 cell surface marker and specific for myelin, the protective layer of nerve fibers that is destroyed in MS.

Sites of infection showed a chronic inflammatory profile with brain-resident memory T-cells — which protect against recurrent or reactivated infection — containing CCL5 (also known as RANTES). This pro-inflammatory molecule has been suggested to be involved in myelin formation and cellular metabolism.

“Early-life infection of mouse brains imprinted a chronic inflammatory signature that consisted of brain-resident memory T-cells expressing the chemokine (C-C motif) ligand 5 (CCL5),” the researchers wrote.

Researchers then found that blocking CCL5 signaling using OB-002, Orion Biotechnology Canada’s CCR5 receptor blocker, prevented the formation of brain lesions in the MS mouse model.

Of note, in mouse and human brains, T-cells containing CCL5 are mainly located at sites with activated microglia — innate immune cells in the central nervous system associated with the development of MS lesions and with myelin loss.

Overall, the results showed that “transient brain viral infection early in life worsened lesion development and symptoms in a mouse model of autoimmune disease,” and that “autoimmune lesions were spatially associated with areas of previous viral infection in mice,” the researchers wrote.

“Mechanistically, early-life viral infection induced a persistent population of CCL5–expressing brain-resident memory T-cells that promoted a long-lasting proinflammatory environment. Blockade of CCL5 signaling prevented the increased predisposition to autoimmunity in the mouse model,” the team added.

“It is very exciting to have identified a possible pathway linking virus infection early in life to MS pathology, and intriguing that it should be dependent on the activation of a single chemokine receptor,” Doron Merkler, the study’s senior author and a professor at University of Geneva and University Hospitals of Geneva, said in a press release.

Oliver Hartley, a study co-author and Orion’s vice-president for drug discovery, added: “We are thrilled to see that OB-002 shows such high efficacy in this preclinical context. These data provide a clear rationale to move forward with the development of OB-002 as [a] novel agent for the treatment of MS.”

27 comments

  1. Rhonda says:

    Jen, I had Measles, German Measles, Chicken Pox, and Whooping Cough before age 4. I am 61, so there were no vaccines.
    I also wondered if the early exposures were part of my MS puzzle.
    Very intetesting article.

  2. Noai says:

    A classmate and myself in college both came down with H1N1 flu and then soon after developed autoimmune responses, mine turned out to be MS. Could there be a link there?

  3. Jean says:

    The last fever I had was when I had measles when I was twelve. I have also wondered about a connection with that and my MS in diagnosis in adulthood.

  4. Michelle lalonde says:

    I also have ms I’m 60 was diagnosed 30 yrs ago only took docs 10yrs to figure it out?anyway I also beleive that it could be viral infections at my young age I had many lots of strep throat and bad case of measles and lots of cold sores was always sick and no one had any idea about ms back them I still suffer from unknown infections plus strep urinary cold sores bad ones rashes unknowen and there was a huge study done on traumatic events maybe being a part of ms in young people I had that to omg so many in knowens wish scientists could connect the dots all the best to all the poor people suffering with this painful depressing life stopped way to short 😂

    • Mary says:

      I was diagnosed 16 years ago at the age of 30. As a child I had a bad case of chicken pox although I was vaccinated. I had many cases of cold/canker sores and UTIs/kidney infections, and severe mono my first year of high school. I am also JC positive.

    • Pam Ripperger says:

      Michelle I’ve also had strep throat as a teenager til 17! Also flu as an infant in Chicago flu Epidemic in 1958! I’ve always believed what the scientists are now saying! I’m 61 yrs old, diagnosed in 1993. I’ve had mild case of MS, very lucky. Can’t walk 4 first time because of Air conditioner going out in 120 degree weather in desert where I live in Arizona in the United States. That happened 21/2 yrs ago still not walking! Otherwise healthy. I was told by pain foundation staff to take Vitamin D3 5000 iu’s a day. I have not been sick & no flu 4 over a year! Try it, gel caps everywhere & inexpensive to buy! Let me no if works 4 you! Pam Ripperger from Scottsdale AZ

      • Camilla says:

        I take vitamin D3 50000 once a week. Right now I fatigue with cognitive issues. I’m on ocrevus and not die until next week for my 3rd infusion. Other than that I’m good.

  5. Michelle lalonde says:

    I would like to connect with a female or male who has suffered with ms symptoms just to talk about different possible siulotions to my unexplained symptoms for the last 30 yrs one hard to deal with question that is so frustrating is how friends family have the opinion that I look well so there fore I am well I’m not well and it’s so hard hiding my real health problems? Please any one who would like to chat please do I’m a 60yr old femal divided still walking most day but live alone family lives in Calgary and have so many unanswered question thanks Michelle lalonde

  6. Tracy Hoff says:

    My body was never the same after getting the shingles. Six years later, I was diagnosed with MS. I wasn’t young though when I got the shingles, I was 37

  7. PAMELA MALDONADO says:

    Wow I’ve always wondered about illness I had as a child and tried my hardest to make a connection. The last time I was sick (before my MS) I had a massive migraine with some coughing. I never got sick much besides a cold here or there with coughing! I always had some sort of cough if I was sick…

  8. Shannon says:

    I had a severe case of mononucleosis when I was 18. I never regained my stamina and my immune system tanked. I was diagnosed with MS when I was in my late 40’s. I believe the myriad of health issues I have experienced over the years are all connected.

    • DEC says:

      I had mononucleosis at age 17. It was the sickest I’ve ever been in 59 years. I first experienced MS symptoms at 25. ( dizziness, vertigo, numbness, etc) For ~ 6 months I had symptoms that were diagnosed as neuropathy or just a pinched nerve. (I knew it wasn’t a pinched nerve. MS was never mentioned.) I then had a 25 year respite. The above systems came back periodically at age 50. It took 2 years to get a MS diagnosis at age 52. My neurologist really thought it wasn’t MS and did a lumbar release and MRI to rule out MS. Both procedures overwhelmingly indicated MS. I’ve had the diagnosis and medication for 7 years. In the scheme of things, my neurologist and I think I’m doing well. Fatigue, memory issues, and some dizziness are on and off issues, but I go to work every day and function fairly well. I’m very thankful! ( I have RRMS.)

  9. Was there a specific “viral infection” or is it just any “viral infection” because 100% of children get a viral infection, if not multiple viral infections in their early years.
    This basically proved nothing.

    • Angie says:

      Zachari, I was thinking the same thing. What 40/50/60/70 year old hasn’t had the flu, chicken pox, etc. It would be helpful if the article indicated which “viral infections” caused the MS like symptoms.

  10. Gail says:

    The article left many questions, as it didn’t point our which viral infection they’re talking about, however, note that it said an infection “early in life.” It may be that those who are especially susceptible to viruses may have had one as children that they’re not even aware of.

  11. America Quinn says:

    I got my first flu shot when I was 39. I developed tingling and numbness and weakness in my legs. I ended up in the hospital 5 days getting steroid treatment They called it transverse myelitis. Next year I took another one the exact same thing happened I finally got diagnosed with MS. I haven’t taken another one since but it is too late.I believe it was that flu vaccination!

    • Camilla says:

      I was diagnosed with transverse myelitis in 2003 then MS in 2016. Prior to 2003 I had an unknown illness that caused me to lose a lot of weight. 165 lbs down to 118 lbs in 3 months. Since I couldn’t keep anything down not even ice chips. I was on an iv for a few months. Drs thought it was my gall bladder and took it out but I had no improvement
      Then one day I could drink water without vomiting.
      I had the diagnosis of TM in 2003, i got shingles in 2012 then MS in 2016.

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