Phoenix Rising: The Gift That Keeps on Giving All Year Long
This holiday season Jody Smith turns her eyes to the people of Phoenix Rising and gives thanks for you all ...
Discuss the article on the Forums.

Theoretical and practical treatments for neurogenesis? (Dr Hyde / HFME / Ramsay-ME)

Discussion in 'General Treatment' started by Jesse2233, Jul 7, 2017.

  1. Jesse2233

    Jesse2233 Senior Member

    Messages:
    1,734
    Likes:
    4,379
    Southern California
    Dr Byron Hyde of Ottawa and Jodi Basset of HFME both believe in a very narrowly defined definition of ME I'll refer to as Ramsay-ME (named after Melvin Ramsay).

    In a nutshell Ramsay-ME is seen as distinct from CFS, in that it always involves:
    • Sudden onset following an acute flu-like illness
    • An enterovirus recovered from stomach tissue
    • A diffuse brain injury of a certain type (as seen on a SPECT / PET / qEEG)
    Dr Hyde famously offers no treatment. He says that those who typically recover are children or adolescents (presumably because they have better mechanisms for neurogenesis), or those with mild impairment (injury appearing on just one side of the brain).

    For the purposes of discussion, let's address Ramsay-ME as a potentially distinct disease. If this is true, then what treatments / cures are possible?

    ---------------------------

    Note: The purpose of this thread is not re-litigate the validity of Dr Hyde's definition as that's been done on other threads. Many (if not most) ME/CFS patients and doctors disagree with Dr Hyde's strict criteria. Ultimately he may be wrong and researchers like Dr Naviaux and Prof Lloyd may be right in that there are many paths to the same disease.

    ---------------------------

    Some of my thoughts:

    For Dr Hyde, Ramsay-ME seems to be brain damage from an enterovirus, full stop. That brain damage then creates all of the multisystemic downstream derangements.

    This model seems akin to post-encephalacy as seen in the aftermath of severe meningitis but with different loci in the brain. Another conceptual model might be post-polio syndrome (again with different loci).

    It's unclear if Dr Hyde feels a chronic virus, autoimmunity, and/or auto-inflammatory states are ongoing factors. For the purposes of discussion let's assume they're not (and that some of the non-responders to antivirals/antibiotics, immunomodulators, and immunosuppressants in fact have Ramsay-ME).

    Again assuming it's brain damage, then what can be done theoretically or practically to encourage neurogenesis?

    Some treatments that come to mind:
    • HBOT
    • Neurofeedback therapy
    • Ketamine
    • Aggressive rest therapy

    • Neuronal stem cell therapy (theoretical)
    • Cybernetic neuronal replacement (theoretical)
    • Nanobotic repair (theoretical)
     
    Sancar likes this.
  2. halcyon

    halcyon Senior Member

    Messages:
    2,307
    Likes:
    5,391
    If you haven't seen it yet, Hyde put out this document in addition to his recent update to his definition. It goes into more detail about what he believes is the nature of the injury in ME brains. He seems to believe that the bulk of it is vascular.
     
  3. Alvin2

    Alvin2 If humans were rational...

    Messages:
    1,308
    Likes:
    3,657
    Lots of things can stimulate neurogenesis
    Even exercise reportedly promotes neurogenesis (to the bane of us ME/CFS people)
     
    Last edited: Jul 7, 2017
  4. Jesse2233

    Jesse2233 Senior Member

    Messages:
    1,734
    Likes:
    4,379
    Southern California
    Wow thanks Halycon haven't seen that. What do you think it implies in terms of treatment?

    Edit:

    Here's what Dr Hyde says in his new document:
    So what might that treatment look like?
     
    Last edited: Jul 7, 2017
  5. ScottTriGuy

    ScottTriGuy Stop the harm. Start the research and treatment.

    Messages:
    1,089
    Likes:
    4,398
    Toronto, Canada
    Kenshin and Jesse2233 like this.
  6. ScottTriGuy

    ScottTriGuy Stop the harm. Start the research and treatment.

    Messages:
    1,089
    Likes:
    4,398
    Toronto, Canada
    Thanks for pointing us toward Hyde's new doc @halcyon

    Many good quotes to extract from an advocacy approach.
     
    Jesse2233 likes this.
  7. adreno

    adreno PR activist

    Messages:
    4,841
    Likes:
    11,024
    A search for compounds that induce BDNF or NGF should provide you with plenty of options.
     
    Sancar and Jesse2233 like this.
  8. Jesse2233

    Jesse2233 Senior Member

    Messages:
    1,734
    Likes:
    4,379
    Southern California
  9. wastwater

    wastwater Senior Member

    Messages:
    959
    Likes:
    654
    uk
    I didn't know he thought it was caused by enterovirus,I always followed the rest about acute onset and thyroid involvement
     
  10. dreampop

    dreampop Senior Member

    Messages:
    222
    Likes:
    525
    Lion's Mane, for example, serves this purpose. However, Hyde's theory is the the blood vessels are damaged, and asfai BDNF and NGF promote Neuron growth and differentiation not vascular restoration. That would be angiogenesis.

    As Halcyon pointed out, Hyde's focus is on the blood vessels in the CNS being damaged. Any damage to the brain comes from lack of oxygen/nutrients starving the areas near the vascular damage. With PEM causing temporary worsening of those factors through vascular spasms. That damage, the vascular cuffing, is caused by leukocyte blockages, which he mentions, and I have no idea how you would treat that and presumably he doesn't either or he would do so. Another question I have is why are/would the cuffing be sustained.

    I think that's what he's saying if I read it correctly.
     
    Last edited: Jul 7, 2017
  11. Jesse2233

    Jesse2233 Senior Member

    Messages:
    1,734
    Likes:
    4,379
    Southern California
    @dreampop

    Looks like monoclonal antibodies are being tested in people with strokes linked to leukocyte cuffing. Enlimomab was tested with poor results, not sure about others

    This updated model may actually link Hyde's work to Rituxan
     
    Sancar and dreampop like this.
  12. dreampop

    dreampop Senior Member

    Messages:
    222
    Likes:
    525
    Looks like your better at google than me, I couldn't find anything for cuffing when I tried.
     
  13. Jesse2233

    Jesse2233 Senior Member

    Messages:
    1,734
    Likes:
    4,379
    Southern California
    lol just got lucky
     
  14. halcyon

    halcyon Senior Member

    Messages:
    2,307
    Likes:
    5,391
    From what I've read you will see this type of vascular cuffing and filling of the perivascular spaces with infiltrating immune cells in viral encephalitis. So in theory removing the enterovirus infection in the CNS should stop the cuffing.
     
    Jesse2233 likes this.
  15. Jesse2233

    Jesse2233 Senior Member

    Messages:
    1,734
    Likes:
    4,379
    Southern California
    Is that true of post viral encephalitic states as well?
     
  16. halcyon

    halcyon Senior Member

    Messages:
    2,307
    Likes:
    5,391
    Not sure.
     
  17. Hip

    Hip Senior Member

    Messages:
    9,517
    Likes:
    15,086
    In terms of the type of brain cells that enterovirus can infect, this appears to be restricted to astrocytes and neural progenitor cells. Refs: 1 2 Enterovirus does not infect the mature neurons of the brain.

    I believe this is because in the brain, only astrocytes and progenitor cells possess the coxsackievirus and adenovirus receptor (CAR), which is a crucial receptor for coxsackievirus B that it uses to enter cells.

    Since astrocytes perform very important housekeeping roles in the brain, a chronic infection in the astrocytes could conceivably lead to many brain dysfunctions. And chronic infections of progenitor cells might conceivably lead to problems as well.

    Neural progenitor cells are the specialized stem cells of the brain, and they are located in certain pockets in the brain. When new neurons are required, progenitor cells will migrate from these pockets into the appropriate positions in the brain, and turn into neurons (this is the process of adult neurogenesis). I believe the two weeks that it sometimes takes for SSRI antidepressants to start working relates to the approximate two week time interval it takes for progenitor cells to migrate into place in the brain (SSRIs stimulate neurogenesis).

    I have wondered whether a chronic enterovirus infection in these progenitor cells might lead to dysfunction or inhibition of neurogenesis.

    The main neurotrophic factors that stimulate neurogenesis are BDNF, NGF and GDNF, and various supplements can stimulate these: noopept increases NGF and BDNF, idebenone promotes NGF, rehmannia glutinosa boosts GDNF, ibogaine increases GDNF, and the supplement 7,8-dihydroxyflavone (7,8-DHF) is a potent BDNF mimic. I have tried all of these, but did not notice any significant benefits.

    Of course though, if the progenitor cells are already infected with smoldering non-cytolytic enterovirus infections, then as these cells migrate into position and morph into mature neurons, those new neurons might conceivably be dysfunctional due to the non-cytolytic infection they may contain.

    Though the fact that full blown ME/CFS can appear within a few days of being infected with enterovirus suggests possibly dysfunctional neurogenesis is not playing much of a role in ME/CFS, because as mentioned, the timescale for creating new neurons is a few weeks, not days.



    In the brain autopsy study of Dr John Richardson, as well as finding enterovirus in a small fraction of the glial cells in the brain (most glial cells are astrocytes), he also found enterovirus in the fibroblast cells in the walls of the small blood vessels of the brain. The former finding confirms the understanding that the only brain cells that we know can be infected with enterovirus are the astrocytes and progenitor cells.

    The latter finding perhaps ties in with @halcyon's post about Dr Hyde thinking the bulk of the brain problem in ME/CFS is vascular. I am not sure if these fibroblasts in the walls of the small blood vessels are considered part of the brain, or just part of the vasculature of the brain, but a chronic non-cytolytic enterovirus infection in these fibroblast cells might conceivably lead to vascular dysfunction in the brain. Mouse fibroblasts are shown to be capable of hosting a chronic non-cytolytic enterovirus infection.

    Interestingly, Borrelia can also infect human fibroblasts. Ref: 1

    An intriguing thing I read about fibroblasts is the research that indicates these cells play an important role in determining whether inflammation resolves, or continues as chronic persistent inflammation. So this made me wonder whether infected and dysfunctional fibroblasts in the brain's small blood vessels might be driving chronic neuroinflammation in ME/CFS.


    I did look into what might be done to specifically fight off an non-cytolytic enterovirus infection in fibroblast cells, but could not find much. Azithromycin, an immunomodulatory antibiotic that is sometimes beneficial for ME/CFS, is known to accumulate in high concentrations in fibroblasts; but whether that explains its benefits for ME/CFS I don't know.
     
    Last edited: Jul 9, 2017
    Sancar, Hutan, halcyon and 1 other person like this.
  18. Jesse2233

    Jesse2233 Senior Member

    Messages:
    1,734
    Likes:
    4,379
    Southern California
    Thanks @Hip, as usual very interesting and comprehensive

    any thoughts on how we might contextualize non-cytolytic infections of astrocytes and neural progenitor cells with the pharmaceutical brain tuning done by Jay Goldstein and his sometimes rapid results?
     
    Sancar likes this.
  19. Hip

    Hip Senior Member

    Messages:
    9,517
    Likes:
    15,086
    I am not clear on how these infections would link to Dr Jay Goldstein's treatments. I think Goldstein's treatments were more palliative than curative, perhaps helping in some patients to address neurotransmitter imbalances or to address the central sensitivity syndrome (neurosomatic disorder) that he thought was part of ME/CFS, but not really addressing any underlying cause.

    I found it interesting that a mouse study of coxsackievirus B-infected astrocytes showed that these cells secreted the pro-inflammatory cytokines IL-1β, TNF-α and IL-6.

    So those cytokines might be a factor driving brain inflammation in ME/CFS. I did look into supplements that could inhibit these pro-inflammatory cytokines from astrocytes, and supplements that may help include: Rehmannia glutinosa steamed root, dandelion, alpha lipoic acid and resveratrol. See the astrocyte section of this post. But I can't say I noticed much when I tried these supplements.
     
    WestCoastSlamDance and halcyon like this.
  20. Jesse2233

    Jesse2233 Senior Member

    Messages:
    1,734
    Likes:
    4,379
    Southern California
    It's interesting that the proinflammatory cytokines show up again. I suppose the question is whether or not they're protective or harmful and thus whether or not to try and inhibit them.

    I'm reminded of @StrayCat's remarkable account of his friend's recovery using Actemra, an IL-6R monoclonal antibody.

    And of course there's Mady Hornig's speculation that use of drugs like Cosentyx, an IL-17a monoclonal antibody, might be an effective treatment
     
    Last edited: Jul 9, 2017

See more popular forum discussions.

Share This Page