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Nanoparticles Stop Multiple Sclerosis In Mice

Posted by samzenpus on from the working-on-a-cure dept.

HangingChad writes "Scientists have used nanoparticles covered in proteins to trick the immune system to stop attacking myelin and halt the progression of multiple sclerosis in mice. The nanoparticles, about 200 times thinner than a human hair, are made from the same material as dissolving stitches. Scientists compare the process an immune system 'reboot'. The process keeps the immune system from treating myelin as an alien invader and to stop attacking it."

50 comments

  1. Not quite by Smallpond · · Score: 4, Informative

    "We administered these particles to animals who have a disease very similar to relapsing remitting multiple sclerosis and stopped it in its tracks"

    The article does not claim that this works for MS, just diseases similar to MS.

    1. Re:Not quite by fuzzyfuzzyfungus · · Score: 5, Funny

      "We administered these particles to animals who have a disease very similar to relapsing remitting multiple sclerosis and stopped it in its tracks"

      The article does not claim that this works for MS, just diseases similar to MS.

      Given that the research is in a mouse model, you can be assured from the get-go that it isn't 100% identical. Model organisms are always a compromise between accuracy, availability, speed, cost, and not getting sent to jail for experimenting on orphans...

    2. Re:Not quite by craigminah · · Score: 4, Funny

      Let's hope this doesn't prompt a huge influx of mice moving into the Chicago area since they seem to have the best lab-rat health care in the nation.

    3. Re:Not quite by wonkey_monkey · · Score: 1
      The article does also say this, in the first paragraph, but premably due to some over-excitement by a journo:

      halt disease progression in mice with relapsing remitting multiple sclerosis (MS).

      Also:

      The article does not claim that this works for MS, just a disease similar to MS.

      FTFY :) After all, MS is a member of the set of diseases similar to MS.

      --
      systemd is Roko's Basilisk.
    4. Re:Not quite by Chewbacon · · Score: 1

      And no mention of human trials means they're still a long ways off. On the right track, perhaps, but don't email this to your friend/family with MS yet as even a light at the end of the tunnel.

      --
      Chewbacon
      The Bible is like Wikipedia: written by a bunch of people and verifiable by questionable sources.
    5. Re:Not quite by wonkey_monkey · · Score: 1

      but premably due to some over-excitement by a journo:

      Good word, premably.

      --
      systemd is Roko's Basilisk.
    6. Re:Not quite by interkin3tic · · Score: 1

      Not even orphan children. MS symptoms appear in adults. So even if you're fine with injecting orphan children with chemicals to see what works, then cutting up their brains, you should be offended at how ineffective that would be.

    7. Re:Not quite by dugjohnson · · Score: 1

      You can get sent to jail for experimenting on orphans? Oh bother.

      --
      My brain is overly lubricated
    8. Re:Not quite by interkin3tic · · Score: 2

      MS can take years to progress, especially with treatments already available, so I think this does in fact provide possible hope for current MS sufferers. Preliminary results are more promising than no progress. Current sufferers might also be interested in participating in the clinical trials.

    9. Re:Not quite by Anonymous Coward · · Score: 0

      Even children can have MS. Pediatric MS

    10. Re:Not quite by interkin3tic · · Score: 2

      My mistake, thank you. But if you were going to do a clinical trial in humans, you'd be even more foolish to try using children with MS, as the number of diagnosed children with MS is so much smaller than adults.

    11. Re:Not quite by reverseengineer · · Score: 3, Informative

      The researchers involved used a disease called experimental autoimmune encephalomyelitis (EAE). This is a disease with many general similarities with multiple sclerosis (being autoimmune responses against myelin), but there are differences in the course of the disease versus MS. EAE is considered to be closer to a rarer human disease, acute disseminated encephalomyelitis (ADEM) than to MS. Nevertheless, EAE has been used for decades as a model for autoimmune diseases, as it has the major advantage of being able to be reliably induced in animals. The method of immune system modulation used in this study seems general enough to apply to similar autoimmune disorders, but that has not been actually established with studies yet.

      --
      "FDA staff reviewers expressed concern about the number of patients who were left out of the study because they died."
    12. Re:Not quite by Stirling+Newberry · · Score: 1

      Just call them terrorists and software pirates, then its OK.

      --
      Fugue for Aaron Swartz
  2. You probably don't know much about MS. by Anonymous Coward · · Score: 5, Insightful

    Good for you. Don't dwell on diseases you don't have.

    Let me explain it a little bit:

    Everything you know of the world comes through your nerves. Every way that you can interact through the world also runs through those same nerves.

    Imagine being unable to trust that.

    Your symptoms vary. Perhaps you can't tell if your foot is on the floor, or if you're urinating or not. Perhaps hot doesn't feel hot anymore, or cold feels hot also. Perhaps it's just pins and needles pains racing up your extremities at random and frequent times.

    There are multiple types of MS. People don't have the same symptoms; it depends on where the lesions in your nervous system are. If they're on a part of the brain that controls motion, expect to be unable to do things that regular people can. You may be in a wheelchair or suddenly fall down a lot. If they're on a part of the brain that controls speech, expect to be unable to communicate, and to forget or misuse common words. If they're on a part of the brain that controls emotion, expect people to treat you like you're crazy when you break down crying in public.

    Some people have the "progressive" MS that gets worse and worse until they are left in a special electric wheelchair, unable to do much more than manipulate a joystick to move and communicate.

    Some die, especially those who get it later in life or are male.

    For all, there is a sense of helplessness. The part of you that you think is you, the brain and the nerves that construct all you know of the world, is itself corrupt.

    Expect helplessness, rage and perhaps hatred of any deities you once believed in.

    Science has so far been unable to do anything about this disease.

    The day they can will be a day of joy.

    1. Re:You probably don't know much about MS. by wonkey_monkey · · Score: 2

      Replying due to lack of mod points, but with good karma which will hopefully lead more people to the parent until it gets probably modded up.

      --
      systemd is Roko's Basilisk.
    2. Re:You probably don't know much about MS. by JackieBrown · · Score: 4, Informative

      My wife has progressive MS. Taking Tysabri helped slow it down a whole lot but she had to stop since she tested at risk for PML.

      It has been a frustrating and traumatic 15 years for her but she has managed to stay more upbeat than I would have and her faith in God and in her family is stronger than anyone I know.

      It is an difficult disease to explain to people for the very reasons you posted. The treatments are also rapidly changing so it is important to find a doctor that specializes in MS. Us switching doctors is probably the reason my wife can still walk.

    3. Re:You probably don't know much about MS. by Anonymous Coward · · Score: 4, Informative

      Some die, especially those who get it later in life or are male.

      ...

      Science has so far been unable to do anything about this disease.

      They have been able to do quite a bit. They haven't cured it but depending on how aggressive your doctor is, it really slowdown the progression. I've had MS since 1998. My primary physician, initially thought I was making up the symptoms, or maybe it was a spinal injury.

      The first neurologist basically said that I COULD go on Avonex, but it was up to me. My wife, being a nurse, said to get on it immediately. So I started with avonex once a week. She also started looking for a doctor that was going to be more aggression with treatment, since, as you pointed out, can be much worse in males.

      My second neurologist, increase the avonex to every 5 days, and also put me on Imuran (a medicine typically used after transplants to help prevent rejection). I think it was a few years later, when there was some research about steroids, when he put me on a high dosage of steroids once every 3 months (160mg orally - talk about roid-rage, the littlest things would set me off for a week or so after the medicine).

      I've had some relapses, but nothing serious, with is great after 14 years. If something like these nanoparticles work out, that would be even better.

    4. Re:You probably don't know much about MS. by Anonymous Coward · · Score: 1

      A guy I know used to work in an HIV vector lab at a biotech company. He claims they had a working cure for MS perhaps 8-10 years ago, but they studied the economics and the FDA would never allow it to be brought to market for less than the potential revenues.

      Apparently the technology used is a trade-secret in one of their ventures that is commercial, so they couldn't release it as pure research either without sinking the company.

      He's fairly critical of the company in most respects and he doesn't criticize them for making that call (he faults the FDA instead), so if he were making it up, that would contradict the theme of his narrative.

      Anyway, that's all I know about the approach: HIV-vector gene therapy. Perhaps you could see if you could find a lab working on a similar approach.

      A/C to protect the blabbermouth.

    5. Re:You probably don't know much about MS. by StikyPad · · Score: 1

      14 years with no progression? A skeptic might wonder if you had/have MS at all and whether your original doctor was right to be reluctant with aggressive treatment. It's unfortunate that there are no proof-positive tests for MS.

      --
      https://www.eff.org/https-everywhere
  3. Promising but years from rollout by Fencepost · · Score: 4, Informative

    So far they've only done a Phase 1 trial which is to prove that it's not harmful, and the researchers called it "hideously expensive" at $1 million for 10 patients. If it shows clinical promise in Phase 2 and beyond, that price is likely to drop quite a bit and quite frankly the available MS treatments are also very expensive - if a single treatment is $100,000 but works for 5+ years, it may still be cheaper than what's currently available.

    More information in an NBC News article: http://vitals.nbcnews.com/_news/2012/11/18/15246299-new-approach-could-treat-ms-other-autoimmune-diseases?lite

    And the original article (for those willing to cough up $32 for a single article or with a subscription to the Nature Biotechnology journal): http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.2434.html

    --
    fencepost
    just a little off
    1. Re:Promising but years from rollout by brianerst · · Score: 2

      That $1 million for 10 patients was for the live cell test on humans. The PLG (poly-lactide-co-glycolide, used in resorbable sutures) version tested on mice would be orders of magnitude cheaper.

      Sounds like they just take some bits of myelin, soak them in nano-structured PLG which latches on to them and then inject that into the bloodstream, where it migrates to the spleen and reeducates the next generation of T-cells. Very promising.

    2. Re:Promising but years from rollout by JATMON · · Score: 1

      My wife has MS and is taking Rebif. The last time that I checked, our insurance was covering almost $5k/month for the cost of Rebif. That would equate out to almost $300k over 5 years which is 3 times that cost of the treatment. After having to deal with insuracnce companies for the 8+ years that my wife has been living with this, I feel confident that they would rather pay the $5k/month than the one payment of $100k.

  4. Any immunologists about? by fuzzyfuzzyfungus · · Score: 3, Insightful

    What puzzles me(admittedly a layman) is that this procedure reduces rather than exacerbates the autoimmune response. If the organism has MS, the immune system is already getting jumpy about myelin, and then they inject something that(at first glance) sounds more like a myelin vaccine than anything else, but in this case the reaction to myelin is shut down.

    Is it just a matter of being attacked by macrophages in the spleen, rather than elsewhere, or are there specific properties that the nanoparticles have to posses in order to be coded as harmless debris, rather than pathogens, during their destruction by macrophages(on a different note, I wonder if there are any viruses or bacteria capable of down-regulating immune responses to themselves by sending suitably modified cells into this spleen breakdown process? That would be sneaky...)?

    1. Re:Any immunologists about? by gatesstillborg · · Score: 2

      If I am not mistaken, and others please correct me if I am wrong, the essential trick here is that the particles are mobile, and thus can make it to the spleen, which is the key to making the spleen think that they (containing myelin antigens) are just debris from dead blood cells and thus not suitable for encoding (antibody) attack. Apparently, the spleen is able to inactivate the encoding of antibodies for materials it contacts directly?

    2. Re:Any immunologists about? by More+Trouble · · Score: 3, Informative

      Immature B-cells are trained in the spleen:

      http://en.wikipedia.org/wiki/B_cell

      Immature T-cells are trained in the thymus. Defects in these self-tolerance processes probably lead to all autoimmune disorders.

    3. Re:Any immunologists about? by Joe+Torres · · Score: 3, Informative

      I only glanced through the paper and I have a fellowship application to finish, so I'll be quick with this response.

      The process the researchers are trying to take advantage of is immune tolerance (https://en.wikipedia.org/wiki/Immune_tolerance). The authors state that the decrease in symptoms is partially due to the activity of regulatory T cells (https://en.wikipedia.org/wiki/Regulatory_T_cell). Regulatory T cells are a type of T cell that inhibits the immune response to certain types of antigens (foreign things that aren't harmful or parts of your self that your immune system shouldn't have responded to in the first place).

      Viruses and bacteria (as well as cancer) can and do take advantage of immune tolerance (I'm not sure about this specific mechanism) in an attempt to avoid immune destruction and this is thought as a possible mechanism for the induction of autoimmune disease.

    4. Re:Any immunologists about? by Anonymous Coward · · Score: 1

      Not an immunologist, but I am an immunology PhD student (2nd year). Prepare for a lengthy response!

      This article is all about taking advantage of peripheral tolerance. In most autoimmune diseases, including MS, the "bad guys" are a combination of lymphocytes: autoreactive B cells, which produce antibody against a self-protein, auto-reactive CD8+ (cytotoxic) T cells, which kill cells expressing a self-protein, and auto-reactive CD4+ ("helper") T-cells, which direct B-cells to produce antibody and attract various inflammatory cells such as neutrophils when they see a self-protein.

      There are 2 levels of tolerance that normally act to prevent this. "Central" tolerance occurs during T and B cell development (in humans, thymus for T cells and bone marrow for B cells). If a T cell or B cell is autoreactive during development and gets overly excited when it it sees self-antigens, it will be deleted. However, not every self-protein is expressed in the "central" tissues, and some autoreactive T and B cells inevitably escape into the circulation. That is when "peripheral" tolerance is supposed to apply. Basically, when a lymphocyte sees its target antigen, it can have a very different response depending on the other factors that are "tickling" it.

      If it sees its antigen while at the same time being tickled by bacterial toxins, inflammatory cytokines, necrotic cell fragments, active dendritic cells, etc, it will likely go into the "oh sh*t" state and start rapidly dividing and produce its effector function against its antigen. This can often be self-reinforcing, as the inflammation helps turns on additional T and B, and the killing of self-cells releases additional self-antigens into the environment.

      If it sees its antigen without experiencing tickling (or better yet, in the context of anti-inflammatory cytokines such as IL-10), peripheral tolerance *should* happen instead. This could involve the T or B cell quietly committing suicide, or it could involve a T-cell developing into a peripheral T-reg which secretes bunches of anti-inflammatory cytokines. This process is also usually self-reinforcing, since resulting T-regs and other "tolerogenic" cells will help suppress future immune responses against that antigen.

      However, peripheral tolerance is pretty hard to control. Whether you get tolerance or inflammation is influenced by a lot of factors, including where the antigen is delivered (sub-cutaneous, orally, intraveinous etc), which immune tissues see it first (lymph nodes, spleen, gut lymphoid, etc), the context where the T or B cells encounters its antigen, etc. We know that apoptotic cell fragments containing an antigen usually tend to produce tolerance against that antigen, but applying this to human diseases has been difficult. Sometimes you can make the inflammation worse rather than resetting to a tolerant state.

      This study was interesting, because they have developed a microparticle approach where antigens tagged to a specific type of small plastic bead seem to be very good at generating peripheral tolerance. It will become very interesting if it works consistently in humans.

      Then again, I haven't passed my quals yet, so what do I know? :)

    5. Re:Any immunologists about? by Anonymous Coward · · Score: 0

      Um, not quite. B-cells are trained in the bone marrow, at least in humans. Spleen plays a rather peripheral role (you can lose your spleen completely with only minor immune system problems). Defects in self tolerance do lead to autoimmune disorders, but there's a lot more to it in addition to B and T cell training.

    6. Re:Any immunologists about? by Guppy · · Score: 1

      Thank you for the lengthy and well thought out summary, Mr. Immunology AC.

      If you're still around, in your opinion, is this comparable to Glatiramer (Copaxone), another immuno-modulatory MS agent which (maybe) acts through peripheral tolerance mechanisms? Looking at the data on Copaxone, it didn't seem to slow the overall progression of the disease, although it improved several parameters important to patient quality-of-life.

    7. Re:Any immunologists about? by Anonymous Coward · · Score: 0

      Hi there, I checked back! I'm not familiar with copaxone, beyond just reading the wikipedia article, but it does seem to be the same basic mechanism: taking advantage of peripheral tolerance mechanisms to generate T-regulatory cells against the MS antigen. Exactly *why* the random peptides that make up copaxaone, and the poly-lactide-co-glycolide nanoparticles used in the parent article, generate this protective response is pretty muddy.

      (off topic..this is my first time posting on slashdot after lurking for awhile, may actually need to get a username now!)

    8. Re:Any immunologists about? by Stirling+Newberry · · Score: 1
      "Defects in these self-tolerance processes probably lead to all autoimmune disorders."

      No that's not at all indicated by the available research.

      --
      Fugue for Aaron Swartz
  5. Re:Sad truth though by wonkey_monkey · · Score: 1

    You seem to be under the misapprehension that everyone in the entire world is a massive douche.

    --
    systemd is Roko's Basilisk.
  6. Transplants? by Anonymous Coward · · Score: 0

    Would this also work for transplants, "teaching" the immune system that the new organ is not to be attacked?

  7. Any other uses? by AlphaWolf_HK · · Score: 2

    I'm not a scientist, but would this have any use for other autoimmune disorders like type 1 diabetes, celiacs, and hell even organ and tissue transplants?

    --
    Careful with names containing L slashdot.org/~AiphaWolf_HK slashdot.org/~AlphaWoif_HK slashdot.org/~AiphaWoif_HK
    1. Re:Any other uses? by Anonymous Coward · · Score: 0

      This is why you should RTFA. It's in the first paragraph.

      "The researchers say the approach may also be applicable to other auto-immune diseases such as asthma and type 1 diabetes. "

  8. "Medical News Today" Unreliable by guttentag · · Score: 3, Interesting
    The article in "Medical News Today" reads like the stuff I used to get from freshman journalism students, not like a professionally-written article. In the first paragraph the article claims managed to halt MS in mice, but then in the third paragraph she quotes one of the authors of the original article in Nature (behind a paywall so we can't read what it actually says unless someone here has a subscription or wants to pay $32). The second paragraph, which should be giving you more information about the subject of the article, throws so much titular crap at you it's hard to figure out who she's talking about, or what relation they have to the work that's being discussed:

    Corresponding author Stephen Miller is the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine in Chicago in the US. He says in a statement:

    It reads more like a transcript of a TV news segment. When you're watching TV they throw these titles at you before the person says anything to give them credibility, so you won't even notice that they never told you whether this guy actually had anything to do with the research. It doesn't work in print because people have the time to read it and realize she's not telling us key info.

    The nanoparticles and Miller and colleagues used are made of a polymer called Poly(lactide-co-glycolide) (PLG), which...

    The nanoparticles and Miller and colleagues? What? And why are random paragraphs in bold? As you scroll through the article there are four different paragraphs that are in bold for no apparent reason. Does she edit her work or just churn it out and post it?

    Slashdot editors should start giving articles from Medical News Today more scrutiny. It seems like it's an office with about 5 people who pay this Catharine Paddock PhD to summarize articles in paywalled journals to drive advertising dollars. The other employees are two CEOs, a marketing director and a "Web Manager." Their other businesses are a database of hospitals, a medical abbreviation glossary, and a medical site ad service. Paddock's PhD is in "Business Administration." Summarizing the paywalled articles to raise awareness is fine, but she seems to be their only author and she can't get her facts straight. If she's contradicting herself in the first three paragraphs and we can't read the source material to verify, then reading MNT articles does nothing but drive ad dollars for MNT. Wait for some more reputable source to sum up the paywalled article and link to that instead.

    1. Re:"Medical News Today" Unreliable by guttentag · · Score: 1
      Somehow in my hunt for the original source material I didn't finish typing my second sentence. What I meant to type was

      ...in the third paragraph she quotes one of the authors of the original article in Nature saying "We administered these particles to animals who have a disease very similar to relapsing remitting multiple sclerosis."

      She contradicts herself in the first three paragraphs of the article. First she says they've stopped MS, then she says they've stopped a disease very similar to MS.

  9. Nanoparticles? by Anonymous Coward · · Score: 0

    It doesn't sound like they had much to do with it...

    "Scientists have used nanoparticles covered in proteins ..."

    1. Re:Nanoparticles? by reverseengineer · · Score: 2

      True, the particles used are an inert support for the proteins, not a treatment in themselves. The idea was to present the proteins as if they were cell-surface proteins which the immune system would recognize and build tolerance for. The original paper's authors performed earlier work with the same proteins attached to white blood cells. This was successful, but in terms of developing a clincal treatment, manufacturing engineered cells presents far more complexity, risk, stability issues, and cost than the manufacture of polymer microparticles coated with the protein. Microparticles, rather than nanoparticles, is the term consistently used throughout the paper, coincidentally. The particles are 500 nanometers in diameter, which is larger than what are usually considered nanoparticles 100 nm).

      --
      "FDA staff reviewers expressed concern about the number of patients who were left out of the study because they died."
  10. HolyGrail candidate... by ElitistWhiner · · Score: 4, Interesting

    ...this treatment's ability to selectively target specific immune intolerances and isolated reset-response within host immune systems promises a way forward to enable immune system regulation for a host of autoimmunity diseases, such as: Coeliac disease, diabetes mellitus type 1 (IDDM), Sarcoidosis, systemic lupus erythematosus (SLE), Sjögren's syndrome, Churg-Strauss Syndrome, Hashimoto's thyroiditis, Graves' disease, idiopathic thrombocytopenic purpura, Addison's Disease, rheumatoid arthritis (RA) and allergies.

  11. I wonder by kilodelta · · Score: 1

    How this applies to allergies which are an abnormal immune response to foreign stimulus. I would love to have a treatment that completely blots out my allergies. I could enjoy spring without drugging myself, and dogs - I could actually have a dog!

    1. Re:I wonder by oyoaha · · Score: 1

      and a cat!

    2. Re:I wonder by kilodelta · · Score: 1

      Believe it or not, I'm not allergic to cats. Just dogs.

    3. Re:I wonder by oyoaha · · Score: 1

      and yet you are a dog person? Somethings about the universe...

    4. Re:I wonder by kilodelta · · Score: 1

      Well, I love both. I have a snoozing feline in my lap right now. But yes, I grok dogs and they grok me. Just can't be around them.

  12. Re:Sad truth though by xQuarkDS9x · · Score: 1

    I have to agree with what AC said though. There's way more dishonest aka "douche" people as you put it then real honest people living in this world.

    --
    You must master your joystick like a fisherman masters bait! - Gimpy
  13. Re:MS is an STD by Billy+the+Mountain · · Score: 1

    Yeah but the original article (from 2002) had a question mark in the title so the answer would be 'No"

    --
    That was the turning point of my life--I went from negative zero to positive zero.