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Potential treatment for neurodegenerative disease in humans

Discussion in 'Other Health News and Research' started by guest, Oct 26, 2010.

  1. guest

    guest Guest

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    I don't know if this has any implications for PWCs since I don't know if "brainfog" plays into this field but it's interesting anyways.

    http://www.sciencedaily.com/releases/2010/10/101018151256.htm

    Crossing Blood-Brain Barrier: New Hope for New Class of Alzheimer's Disease Drugs
    ScienceDaily (Oct. 25, 2010) Finding a drug that can cross the blood-brain barrier is the bane of drug development for Alzheimer's disease and other neurological disorders of the brain. A new Penn study, published in the Journal of Neuroscience, has found and tested in an animal model of Alzheimer's disease a class of drug that is able to enter the brain, where it stabilizes degenerating neurons and improves memory and learning.

    In the normal brain, the protein tau plays an important role in stabilizing structures called microtubules in nerve cells, which serve as tracks upon which cellular material is transported. In Alzheimer's disease and related disorders, tau becomes insoluble and forms clumps in the brain. One consequence of these aggregates is a depletion of normal tau, resulting in destabilization of the microtubule tracks that are critical for proper nerve-cell function.
    Senior authors Virginia M.-Y. Lee, PhD, director of the Center for Neurodegenerative Disease Research (CNDR), and John Trojanowski, MD, PhD, director of the Institute on Aging and CNDR co-director, introduced the concept of using microtubule-stabilizing drugs over 15 years ago to counteract tangles of tau and compensate for the loss of normal tau function. Kurt Brunden, PhD, director of Drug Discovery at CNDR and Bin Zhang, MD, PhD, senior research investigator, are the first authors on this study from the University of Pennsylvania School of Medicineand the School of Arts and Sciences.
    In 2005, the CNDR researchers showed that the anti-cancer drug paclitaxel (Taxol) could improve spinal cord nerve function in mice with tau tangles in their brains, after the drug was absorbed at nerve termini in muscle. "However, paclitaxel and related drugs do not cross the blood-brain barrier" notes Brunden. "So we surveyed a number of additional microtubule-stabilizing agents and discovered that the epothilone class, and in particular epothilone D, readily entered and persisted in the brain."
    "The positive effect of epothilone D on the function of axons and on cognition, without the onset of side-effects offers hope that this class of microtubule-stabilizing drugs could progress to testing in Alzheimer patients in the near future," says Lee.
    "There are very few tau-focused drugs in clinical trials now for Alzheimer's disease," says Trojanowski. "While we and others have urged that pharmaceutical companies should not put all of their eggs in one drug basket to ensure the highest likelihood of finding disease-modifying therapies for Alzheimer's, we hope this successful mouse study of a tau drug will encourage more pharmaceutical companies to pursue programs on tau-focused drug discovery."
    Help from Sponges
    The epothilones are microtubule-binding drugs derived from marine sponges and have been used as anti-cancer drugs because they prevent cells from dividing. They do this by keeping microtubules overly stabilized, which blocks cell division and causes cell death in rapidly dividing cells such as cancer cells. However, since nerve cells do not replicate or divide, they are immune to the toxic effects of microtubule-binding drugs.
    In Alzheimer's disease and other diseases with tau clumps in the brain, the hope is that a microtubule-stabilizing drug will restore the microtubule tracks to their original supportive structure. This led the researchers to give the tau mice epothilone D (epoD) to replace the now unavailable tau.
    Indeed, epothilone D improved the brain function of tau mice, which have tau inclusions in their forebrain, degenerated axons, and broken microtubules. After treating three-month old male tau mice with a low dose of epoD once a week for three months, the mice showed increased numbers of microtubules and improved axon integrity, without notable side effects to organs and immune cells.
    What's more, epothilone D reduced deficits in memory and learning in the tau mice. "EpoD improves cognition in mice affected by neurodegenerative tau pathology. These findings suggest that epothilone D and other microtubule-stabilizing agents hold considerable promise as potential treatments for neurodegenerative diseases in humans,"
    says senior author Amos B. Smith III, PhD, the Rhodes Thompson Professor of Chemistry.
    This research was funded by the National Institute on Aging and the Marian S. Ware Alzheimer Program.
     
  2. Hip

    Hip Senior Member

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    Note that in the Penrose–Hameroff theory of consciousness, tiny tubular structures within cells called microtubules are postulated to be the source of consciousness in the brain.

    From the perspective of this Hameroff–Penrose theory of consciousness, I understand that defective tau proteins might explain the impaired consciousness found in Alzheimer's. Tau proteins stabilize microtubule structures, so in Alzheimer's, when the tau proteins become defective, microtubules then become destabilized, theoretically leading to a dysfunction of consciousness.


    In ME/CFS of course, there is also a dysfunction of consciousness, which is sometimes not so dissimilar to that of Alzheimer's. We call this ME/CFS dysfunction of consciousness "brain fog" or cognitive dysfunction. Now interestingly, it has been shown that autoantibodies to the MAP2 protein are present at least in some ME/CFS patient subsets.

    Like tau proteins, MAP2 also stabilizes microtubules, so if there are autoantibodies attacking MAP2, theoretically this might conceivably also act to destabilize the microtubules, leading to a dysfunction of consciousness

    So it occurred to me that the MAP2 autoantibodies found in some ME/CFS patients might explain, at least in part, the cognitive dysfunction of ME/CFS.
     
  3. peggy-sue

    peggy-sue

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    Scotland
    I can't access the Penrose document. :( Is that Roger Penrose, the philosopher?
    How does his stuff fit in with Gerald Edelman's? the immunologist (and Nobel prize winning scientist)
    I like Edelman. :love: I don't like Penrose.:p

    How do these microtubules work in areas outside the brain, which have consciousness? Are they (the tubules) present in other parts of the body?

    (Recent research has concluded that there is some consciousness in eg. the gut, if I recall correctly.)
     
  4. Hip

    Hip Senior Member

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    Roger Penrose is a mathematician, theoretical physicist, and also a philosopher. Stuart Hameroff is an anesthesiologist who is interested in scientific theories of the nature of consciousness.

    Their theory of consciousness postulates that quantum effects within these tiny microtubule structures generates consciousness. My grasp of this theory is only qualitative; ie, I don't understand the mathematical and quantum theory details, but I have a basic understanding of it. This theory of consciousness has not yet been corroborated by empirical evidence, so it remains to be proven.

    These microtubules are present in all eukaryotic cells, and evidence indicates that microtubules-like structures are also present in bacterial cells. According to Hameroff microtubules can be considered the nervous system of the cell.

    A pdf of the Penrose–Hameroff theory document is here: Consciousness in the universe A review of the ‘Orch OR’ theory (but it's only the first two or three pages that are readable; after that it gets into technically detail).

    I had not heard of Gerald Edelman before.
     
    Last edited: Apr 22, 2014

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