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Possible Cure For MS Turns Common Skin Cells Into Working Brain Cells

Posted by samzenpus on from the from-one-thing-to-another dept.

An anonymous reader writes "Scientists have discovered a way to convert ordinary skin cells into myelinating cells, or brain cells that have been destroyed in patients with multiple sclerosis, cerebral palsy and other myelin disorders. The research, published in the journal Nature Biotechnology, may now enable 'on demand' production of myelinating cells, which insulate and protect neurons to facilitate the delivery of brain impulses to the rest of the body."

47 of 87 comments (clear)

  1. So the next quesiton is.... by plazman30 · · Score: 5, Interesting

    Now that you've made myelin, how do you get it to stick to actual damaged neurons and/or brian cells. If you inject it in there, is it naturally just going to bind to damaged cells?

    1. Re:So the next quesiton is.... by divisionbyzero · · Score: 1

      Now that you've made myelin, how do you get it to stick to actual damaged neurons and/or brian cells. If you inject it in there, is it naturally just going to bind to damaged cells?

      Yeah, exactly. Otherwise I don't think clumps of myelin just floating around the brain are going to be a good thing.

    2. Re:So the next quesiton is.... by OG · · Score: 5, Interesting

      The abstract indicates that the researchers injected the induced oligodendrocytes into mouse brains and they bound to unmyelinated neurons. I don't have access to the article, and I'm not going to pay for it, but perhaps someone else can provide the technical details. Still, it's a question that the authors address.

    3. Re:So the next quesiton is.... by interkin3tic · · Score: 2
      They used "shiverer" mice, a mutant line in which myelin of the central nervous system is affected, and these cells appear to rescue it.

      We studied the ability of 8TF-induced MEFs to myelinate axons of hypomyelinated shiverer (Mbpshi/shi) mice, which completely lack MBP and compact myelin and serve as a model of congenital dysmyelinating disorders...ultrastructural analysis by electron microscopy showed that the cells generated multilayered compact myelin sheaths around hypomyelinated shiverer host axons in slice culture

      If you're wondering, here is a link video showing why they're called "shiverer." Be forewarned, it's a little disturbing to watch them. I say that having done mouse brain research myself. The reeler mice I've seen in person (Er, seen in mouse) are actually kind of cute, they stagger around like they're drunk (not the best video, but here. These shivering mice on the other hand, I don't know. I just want to put them out of their misery.

      Anyway, with that warning here's the depressing link of what happens when your mouse doesn't have enough myelin in its spinal cord.

    4. Re:So the next quesiton is.... by interkin3tic · · Score: 2

      PS. Got off topic there. Anyway, here is the figure in question, I tested it on my phone, that shouldn't be behind a paywall. LM and N are the panels to focus on. It appears that not all the axons are myelinated, but the ones that are look like they're completely ensheathed.

      Searching for "shiver" I didn't see anything about a reduction in shivers in the treated mice. That would have been pretty huge had it rescued the "symptoms" of the condition, so I'm going to assume that at this first pass it wasn't enough to "fix" these mice enough to detect. It would have been really nice had it done that, but this is just a first pass. Hopefully subsequent studies will refine the process to the point where most of the axons are remyelinated, then it may actually fix MS or other diseases.

    5. Re:So the next quesiton is.... by Harvey+Manfrenjenson · · Score: 1

      Thanks for the link. A long time ago, I worked in a lab which did a much less sophisticated version of this experiment. They took oligodendrocyte precursor cells (a cell line called 02A), which were genetically engineered to express some kind of easily-seen marker protein (forget which one). The cells were isolated and cultured (which was a pain in the ass to do) from a special breed of non-shiverer mice with the marker protein. Then they were injected into the dorsal columns of shiverer mice, much like in this figure.

      From what I recall the results were broadly similar to what these guys achieved. Getting the precursor to differentiate and myelinate nearby axons was not a problem-- they did that on their own. The big problem is that they did NOT proliferate in the spinal column and they did NOT migrate around much. So you would get a little patch of myelinated axons around the injection site, like in figures G and H from the link, but of course the rest of sthe central nervous system was unaffected and it had no effect whatsoever on the shiverer mouse's symptoms or or survival.

      The innovation here is that they somehow got skin cells to turn into oligodendrocytes, which is neat. But it doesn't seem to hold much promise as an actual treatment.

    6. Re:So the next quesiton is.... by gzuckier · · Score: 1

      It's always amazing how much of biology is self-assembling. to me, the question is, how do you keep whatever started the disease in the first place from continuing to destroy the new cells?

      --
      Star Trek transporters are just 3d printers.
  2. Re:Obligatory? by Anonymous Coward · · Score: 2, Funny

    Q: How did Microsoft break Volkswagen's world record?
    A: Volkswagen only made 22 million bugs!

  3. Re:Obligatory? by i+kan+reed · · Score: 2, Funny

    Here's a first pass:

    What do you get when you cure brain disease?

    No more windows 8.

  4. So now the hungry Zombies will cry: by Anonymous Coward · · Score: 2, Funny

    "Skkiiiinnnnnnn...."

  5. Exobrain by Geheimagent · · Score: 1

    Cool, this will turn your skin into an exobrain.

    1. Re:Exobrain by Reverand+Dave · · Score: 1

      That gives "thinking with your dick" a whole new meaning! "Wow, how'd he solve that equation?" "With his penis..."

      --
      I got here through a series of tubes
    2. Re:Exobrain by K.+S.+Kyosuke · · Score: 1

      Circumcisions will become extinct.

      They'd become the modern equivalent of lobotomy? Well, a part of the population wouldn't notice the difference anyway.

      --
      Ezekiel 23:20
    3. Re:Exobrain by oPless · · Score: 1

      You say this like it isn't happening already...

  6. Cautiously Optimistic by organgtool · · Score: 5, Insightful

    The article wasn't clear on whether or not this could reverse the damage caused by MS or whether it would just prevent further damage. I know several people that suffer from this disease and it's utterly horrible. The worst case is my uncle who went from being in peak physical condition to requiring a cane or wheelchair to get around. He now stutters when he speaks, has trouble holding his head up, and can't keep his eyes still enough to even focus on words while trying to read. This disease slowly takes away all of your faculties and strips you of all autonomy and independence and a cure for it can't come fast enough.

    1. Re:Cautiously Optimistic by stereoroid · · Score: 4, Funny

      The damage done in MS is to the nervous system, and all that new myelin could do would be to prevent further damage. That's still very much worth pursuing if it allows a healing process to take place - whether natural or another man-made therapy.

      --
      (this is not a .sig)
    2. Re:Cautiously Optimistic by Graydyn+Young · · Score: 2

      Even if it only works as a preventative, it could be a huge step up from current treatment. The current standard for treating MS is interferon injections, which are expensive, not very effective, and come with a host of nasty side effects.

    3. Re:Cautiously Optimistic by Anonymous Coward · · Score: 1

      A bit of both, at least if it works -
      For neurones lacking mylin slows signals and increases the capacity for crosstalk among other things, in addition to these problems this can cause connections to be lost eventually leading controlled cell suicide (apoptosis).
      The reduced efficiency will be repaired allowing the neurons left to talk properly again, at least if it works - this should cause some recovery, potentially quite a bit.
      Dead neurons do get replaced but only at a very slow rate, so any neuronal die-off will be left as an issue - but death rates should return to more normal levels for a brain of that age.

    4. Re:Cautiously Optimistic by Anonymous Coward · · Score: 2, Informative

      Untrue. The symptoms of MS are due to demyelination. Current treatments reduce the inflammatory response and therefore further myelin destruction but do nothing to rebuild the destroyed myelin. Remyelinating the neurons is the missing step in MS treatment.

    5. Re:Cautiously Optimistic by Willuz · · Score: 4, Informative

      Exactly right, this is just a way of repairing damage already caused by MS and does not "cure" or slow the disease at all. Still an important step though, since damage is permanent for most people.

      It's easiest to think of MS as mice chewing the insulation off the wiring in your car resulting in short circuits and lost signals. Curing the disease would be getting rid of the mice. This treatment is like taking your car to the shop to have the wiring replaced, but the car is still full of mice that will eat the wiring again. The current treatments for MS just put the mice (mostly) to sleep, but they're still there and could awake at any time and some people's mice are more resistant than others.

    6. Re:Cautiously Optimistic by ceoyoyo · · Score: 3, Informative

      It's not going to prevent further damage. This certainly isn't a cure or potential cure for MS, but if it works well it might help fix some of the damage that's been done. Some. Axons die in MS, and this won't replace them. There's good evidence that a lot of the actual damage is due to neuronal damage and not a failure to remyelinate.

    7. Re:Cautiously Optimistic by meerling · · Score: 2

      In your analogy, you need both to get rid of the mice, and repair the wiring.
      This is part of the solution.
      I have some friends with MS, and even this partial patch job would be a vast improvement, even if it has to be repeated occasionally.

    8. Re:Cautiously Optimistic by meerling · · Score: 1

      It's a treatment that has the potential to restore some functionality. It's kind of like bailing a boat. It doesn't fix the root problem, but it might restore some functionality and definitely slows the worsening of the situation and puts off the eventual undesirable termination.

    9. Re:Cautiously Optimistic by steelfood · · Score: 1

      Not sure why you're modded funny. You are probably correct, in that this therapy wouldn't reverse the effects, at least not immediately. Whether the body can heal on its own (albeit slowly), or there needs to be some other complementary procedure that would actively reverse the effects of MS is probably an area that warrants further study.

      Mods? Are you playing mod-roulette today?

      --
      "If a nation expects to be ignorant and free in a state of civilization, it expects what never was and never will be."
    10. Re:Cautiously Optimistic by ceoyoyo · · Score: 1

      Not necessarily. There has been quite a bit of work on transplanting oligodendrocytes and their precursor cells, including stem cells. That hasn't yielded any real results. Other research has shown that there really isn't a shortage of oligo precursor cells. There are some axons that don't remyelinate but a big source of damage seems to be axons that are permanently damaged or die when they're demyelinated.

      It's interesting and might be useful, but it might equally well turn out not to be useful in MS at all.

    11. Re:Cautiously Optimistic by bughunter · · Score: 1

      This research has potential to become a treatment to repair the lesions in the brain caused by MS.

      From the second linked article:

      In multiple sclerosis, the destruction of oligodendrocytes and myelin results in symptoms such as loss of balance, problems moving arms and legs, loss of coordination and weakness, according to the National Institues of Health. Other problems include loss of bladder control, impaired vision, depression, and memory loss.

      To fix these problems, not only must the autoimmune reaction be brought under control, but the myelin must be repaired. That implies producing new oligodendrocytes. Hence, the OPCs, which researchers think could become effective sources of the olgodendrocytes when transplanted. (Transplantion of fully mature cells doesn't seem to work in such studies; the cells seem to need to complete the last step of maturation in their new enviroment to wire into the nervous system.)

      My wife has recurring-remitting MS and suffers from mild to moderate permanent symptoms that remain after her relapses. She takes betaseron to help prevent relapses, but this does not in any way treat the symptoms. Sometimes the lingering effects of a relapse will fade over time as new circuits get wired around the damage, but this never a full recovery. The possibility of regrowing myelin to actually repair this damage would represent a kind of treatment that is currently not available... she'll be excited about this news.

      Your uncle sounds like he has progressive MS, which is much more severe and debilitating. As advanced as his case is, a treatment like this may not be able to completely repair the damage he suffers, but it would certainly offer an improvement in his quality of life. Progressive MS patients need the other part of the cure --the prevention of autoimmune damage-- as well as a cure for the damage caused. I wish him the best.

      --
      I can see the fnords!
    12. Re:Cautiously Optimistic by mattack2 · · Score: 1

      Serious question: Does the body repair the wiring (myelin sheath) at ALL by itself?

      Is this just eating the insulation faster than it can regrow, or does it not regrow at all?

  7. 10 LET M$ = "Microsoft" by tepples · · Score: 1

    Some people claim that "M$" is childish. But stories like this are why I still use the abbreviation to fit under the 50-character limit of comment subjects. M$ unambiguously means Microsoft, recalling its beginning as a publisher of line-numbered BASIC interpreters for 8- and 16-bit microcomputers where string variable names ended with $.

    On the one hand, the similarity of the names is a joke. On the other hand, the National Multiple Sclerosis Society did call Microsoft corporation of the year in 1999.

    1. Re:10 LET M$ = "Microsoft" by Runaway1956 · · Score: 2

      Maybe I'm tired, or just having a slow day. The joke nearly went "whoosh" for me. Good one though!

      The residents of Silicon Valley are more confused than usual after a billboard campaign by the National Multiple Sclerosis Society of America used this line in an ad slogan "MS, it's not a software company"... exploiting the fame of a certain company to draw attention to an altogether worthier cause.
      Requests to comment on the campaign have been met by a surly silence by Microsoft, which doesn't relish the association of ideas but is painfully aware that it can't afford to appear insensitive over such an issue.
      Seasoned information technology professionals will have no trouble telling the two MSs apart One is a debilitating and surprisingly widespread affliction that renders the sufferer barely able to perform the simplest task.
      The other is a disease.

      --
      "Windows is like the faint smell of piss in a subway: it's there, and there's nothing you can do about it." - Charlie Br
    2. Re:10 LET M$ = "Microsoft" by spitzak · · Score: 1

      "MS" is also Missisippi, it is the stock symbol for Morgan Stanley, it means Master of Science, and there is quite a few other things it can mean which can be put in the same sentence as Microsoft. So I agree the diatribe against "M$" is stupid, it is a useful abbreviation. I also notice that if somebody says something insulting like "Microsuck" nobody comments, but if somebody says "M$" suddenly out of the woodwork comes all the "oh you are childish! Childish! Childish!" responses. I think it shows desperation by some Microsoft defenders who are not at all secure in their claim that nobody should use "M$".

    3. Re:10 LET M$ = "Microsoft" by Pseudonym+Authority · · Score: 1

      N0P3, 17'5 N07 (H1LD15H 4ND 57UP1D 70 U53 5YMB0L5 1N PL4(3 0F L3773R5 1N 4N 3FF0R7 70 L00K K3WL 47 4LL!

    4. Re:10 LET M$ = "Microsoft" by wordsnyc · · Score: 1

      I was diagnosed with primary progressive multiple sclerosis one year after I dumped Windows XP for Linux. Coincidence, or punishment?

      I am also allowed to make New Jersey jokes because I was born there.

      --
      Sent from the iPad I found in your car.
  8. Re:Terry Pratchett could benefit from this.... by Attila+Dimedici · · Score: 1

    I believe that Terry Pratchett is suffering from a form of Alzheimer's disease. I do not believe that Alzheimer's involves the myelin.

    --
    The truth is that all men having power ought to be mistrusted. James Madison
  9. And I wonder by kilodelta · · Score: 2

    Since ALS aka amaotrophic lateral sclerosis is caused by de-myelnizing of the nerve fibers - you could probably cure that too.

    And since I have a slight risk this is good news.

    1. Re:And I wonder by chooks · · Score: 2

      FYI - ALS is primarily a neurodegenerative disease where the neurons themselves are dying off and not a demyelinating disease where the neurons remain intact but loose their myelin sheath.

      --
      -- The Genesis project? What's that?
  10. Nature Article discussion by Guppy · · Score: 3, Informative

    Just a quick walk-through of the first section of the paper:

    Cell-based therapies for myelin disorders, such as multiple sclerosis and leukodystrophies, require technologies to generate functional oligodendrocyte progenitor cells. Here we describe direct conversion of mouse embryonic and lung fibroblasts to induced oligodendrocyte progenitor cells (iOPCs) using sets of either eight or three defined transcription factors.

    The Slashdot summary and 3rd party source says "skin cells", but the paper indicates the specific cell type used were "mouse embryonic fibroblasts (MEFs)"; specifically, they were MEFs isolated from a transgenic mouse lineage where a specific transactivator had already been engineered into their genome. This transactivator was designed to work together with the introduced Lentivirus vector (a retrovirus, member of the genus to which HIV belongs), carrying the Oligodendrocyte Progenitor Cell (OPC) transcription factors.
    In a later section of the paper, they perform a similar process with "mouse lung fibroblasts" (MLFs), and also test several different combinations of transcription factors.

    iOPCs exhibit a bipolar morphology and global gene expression profile consistent with bona fide OPCs. They can be expanded in vitro for at least five passages while retaining the ability to differentiate into multiprocessed oligodendrocytes.

    Looks like a duck, quacks like a duck. Can be expanded into a flock while still retaining duck-ness.

    When transplanted to hypomyelinated mice, iOPCs are capable of ensheathing host axons and generating compact myelin. Lineage conversion of somatic cells to expandable iOPCs provides a strategy to study the molecular control of oligodendrocyte lineage identity and may facilitate neurological disease modeling and autologous remyelinating therapies.

    Induced OPC cells integrate into their normal niche, insulating neurons (at least at the cellular level). Didn't see much discussion of whether or not it altered the hypomyelinated ("shiver" mouse) phenotype.

    1. Re:Nature Article discussion by interkin3tic · · Score: 1

      The Slashdot summary and 3rd party source says "skin cells", but the paper indicates the specific cell type used were "mouse embryonic fibroblasts (MEFs)"

      Well, fibroblasts are common in the skin, and you can easily get fibroblasts from taking a small patch of skin. You're right that they're not the keratinized cells that make up most of the skin, but they are in the skin.

      Induced OPC cells integrate into their normal niche, insulating neurons (at least at the cellular level). Didn't see much discussion of whether or not it altered the hypomyelinated ("shiver" mouse) phenotype.

      It did restore at least some myelination but not all of the axons, and I didn't see anything about it improving the shivers.

  11. Re:Embryonic Stem Cells by ColdWetDog · · Score: 1

    I am wondering if the federal ban on funding for embryonic stem cells played a role in funding this particular research or even made the scientists redirect their efforts??? Sometimes a seemingly stupid policy has unexpected positive results. We in the US might actually dodge a research black hole by not getting to invested in embryonic stems cells which have many problems the persons on bodies don't.

    Not a whole lot. Converting already differentiated cells (like skin cells) into other cell types or pleuripotent stem cells has always been a hot research topic. Even without the federal funding ban, working on embryonic cells is a PITA. Skin fibroblasts are much easier to deal with. Also, the understanding of how to de-differentiate cells is obviously an important part of understanding developmental biology. If you can run the tape both forwards and backwards you have a better chance of understanding the process.

    The two are complementary approaches. Did the federal ban speed things up? Who knows? Maybe if one researcher hadn't been on that all week bender we would have had the recent advances 20 years ago. If George Bush hadn't been elected twice we might have flying cars by now.... If Obama hadn't been elected, I might be able to buy some shotgun shells..... Oops. Digressing here. Sorry.

    --
    Faster! Faster! Faster would be better!
  12. Re:Terry Pratchett could benefit from this.... by meerling · · Score: 1

    Yes, different disease, different problem. Alzheimer's has a build up of a type of plaque, not a destruction of myelin sheaths as in MS.

  13. Re:Multiple Sclerosis treatment you mean? by meerling · · Score: 1

    You are correct, it is not a cure. On the other hand, it is a very important milestone to a cure. Two things have to be found to create a 'cure' for MS.
    One, is a way to stop the destruction of the myelin. We don't really have that, but we do have stuff that slows it down.
    Two, is a means to repair the damage the disease/disorder did. That's what this treatment may do.
    It's not the ultimate solution, but it looks like it's a big step in the right direction.

  14. Re:Don't forget!! by meerling · · Score: 1

    There are actually several different types of cells in the brain, even though we talk about them collectively as brain cells and rarely differentiate outside of medical and scientific discussions. It's kind of like how most people talk about 'bullets' and gun enthusiasts discuss various types of 'ammo'. Something like a '22 long 32 grain smokeless', which is a bogus example, but only someone that knows a lot about firearms can tell you what is wrong with that off the top of their head.

    Short version, different type of brain cell there buddy :)

  15. Re:Embryonic Stem Cells by meerling · · Score: 1

    I'd say it's slowed it all down as it has prevented the usage of an available resource until there was found a way to create an alternate source. Unfortunately, if you've been keeping track of this stuff on the science & medical sites, you'd know that even though they have been finding ways of restoring pluripotency to cells, the resulting 'stem cells' seem to have defects of various types.
    In short, they just aren't as good as the real thing. Of course, they are still working to improve the induced versions, but for the most part, they don't even know what's wrong.

    IMO, even the partial gains to induced pluripotency research is far outweighed by the loss of stem cell research and the humans that have suffered and died because of the many years of delay in the treatment research for various diseases. Which by the way, has still not been solved since the 'manufactured stem cells' have not proven as capable as the real ones. (Kind of like a cheap plastic Tonca Truck that costs several times the price of the metal Tonka Truck it's a knockoff of.)

  16. Re:Terry Pratchett could benefit from this.... by Attila+Dimedici · · Score: 1

    That is what I was thinking, but I did not want to state it outright since it had been too long since I last looked it up and didn't feel like looking it up this morning.

    --
    The truth is that all men having power ought to be mistrusted. James Madison
  17. Re:Obligatory? by interkin3tic · · Score: 1

    I thought someone was going to reference the turning cells collected from urine into brain cells.

    Maybe someone should piss on the faces of the people who designed windows 8?

    I... I tried.

  18. Multiple Sclerosis by dontgetshocked · · Score: 1

    Since I live the dream, I can only hope that there is some truth to this and that there may be hope for some. I have the rarest kind of MS and so there are NO treatments for it. Research, where you at? Where is my magic pill?

  19. Re:Rebound effect? by Sulphur · · Score: 1

    What happens if the body reacts and tries to compensate? By turning brain into skin, for example?

    A skinhead?

  20. Say NO to Circumcision by eyendall · · Score: 1

    Now we have proof. A guys brain sits at the end of his cock.