Results 1 to 5 of 5

Thread: (Abstract) Harnessing integrated stress response for treatment of MS

  1. #1
    Distinguished Community Member agate's Avatar
    Join Date
    Oct 2006
    Location
    USA
    Posts
    6,718
    Blog Entries
    11

    Default (Abstract) Harnessing integrated stress response for treatment of MS

    From PubMed, February 14, 2016:

    Lancet Neurol. 2016 Feb 9. pii: S1474-4422(15)00381-6. doi: 10.1016/S1474-4422(15)00381-6.

    Harnessing the integrated stress response for the treatment of multiple sclerosis.

    Way SW, Popko B.





    Multiple sclerosis is a chronic demyelinating autoimmune disease of the CNS with no known cure. Although 12 immunomodulatory therapies exist, they have only modest effects on disease progression. The field has therefore focused on the development of alternative treatment strategies, such as enhancement of remyelination and CNS repair.

    Progress has been made on a third, complementary treatment approach that aims to protect oligodendrocytes--and the myelin they generate and maintain--from inflammation-mediated death by enhancing the integrated stress response.

    Studies in cells and in mouse models of multiple sclerosis have shown that this innate protective pathway, which maintains proteostasis, can be harnessed effectively to protect oligodendrocytes and myelin during inflammation.

    With one drug already in clinical development for patients with multiple sclerosis, and several potential therapies under investigation, modulation of the integrated stress response might become an important component of strategies to halt the progression of the disease.




    The abstract can be seen
    here.

    Does anyone know anything about this? What is the "one drug already in clinical development for patients with multiple sclerosis," I wonder?
    Last edited by agate; 02-14-2016 at 03:53 PM.
    MS diagnosed 1980. Avonex 2002-2005. Copaxone 6/07 - 5/10.
    Member of this MS board since 2001.

  2. The following 5 users say "thanks"


  3. #2
    Distinguished Community Member Lazarus's Avatar
    Join Date
    Oct 2006
    Location
    western MA
    Posts
    991

    Default

    This names a drug being tested: GUANABENZ??????

    "Abstract• Introduction• Results• Discussion• Methods• Additional information• References• Acknowledgements• Author information• Supplementary information
    Oligodendrocyte death contributes to the pathogenesis of the inflammatory demyelinating disease multiple sclerosis (MS). Nevertheless, current MS therapies are mainly immunomodulatory and have demonstrated limited ability to inhibit MS progression. Protection of oligodendrocytes is therefore a desirable strategy for alleviating disease. Here we demonstrate that enhancement of the integrated stress response using the FDA-approved drug ​guanabenz increases oligodendrocyte survival in culture and prevents hypomyelination in cerebellar explants in the presence of ​interferon-γ, a pro-inflammatory cytokine implicated in MS pathogenesis. In vivo, ​guanabenz treatment protects against oligodendrocyte loss caused by CNS-specific expression of ​interferon-γ. In a mouse model of MS, experimental autoimmune encephalomyelitis, ​guanabenz alleviates clinical symptoms, which correlates with increased oligodendrocyte survival and diminished CNS ​CD4+ T cell accumulation. Moreover, ​guanabenz ameliorates relapse in relapsing-remitting experimental autoimmune encephalomyelitis. Our results provide support for a MS therapy that enhances the integrated stress response to protect oligodendrocytes against the inflammatory CNS environment.
    Guanabenz ????

    Subject terms: Biological sciences Immunology Neuroscience
    At a glance
    Figures
    First | 1-3 of 7 | Last

    CompoundsAbstract• Introduction• Results• Discussion• Methods• Additional information• References• Acknowledgements• Author information• Supplementary information
    Oligodendrocyte death contributes to the pathogenesis of the inflammatory demyelinating disease multiple sclerosis (MS). Nevertheless, current MS therapies are mainly immunomodulatory and have demonstrated limited ability to inhibit MS progression. Protection of oligodendrocytes is therefore a desirable strategy for alleviating disease. Here we demonstrate that enhancement of the integrated stress response using the FDA-approved drug ​guanabenz increases oligodendrocyte survival in culture and prevents hypomyelination in cerebellar explants in the presence of ​interferon-γ, a pro-inflammatory cytokine implicated in MS pathogenesis.

    in vivo, ​guanabenz treatment protects against oligodendrocyte loss caused by CNS-specific expression of ​interferon-γ. In a mouse model of MS, experimental autoimmune encephalomyelitis, ​guanabenz alleviates clinical symptoms, which correlates with increased oligodendrocyte survival and diminished CNS ​CD4+ T cell accumulation. Moreover, ​guanabenz ameliorates relapse in relapsing-remitting experimental autoimmune encephalomyelitis. Our results provide support for a MS therapy that enhances the integrated stress response to protect oligodendrocytes against the inflammatory CNS environment.

    Subject terms: Biological sciences Immunology Neuroscience

    Genes and Proteins
    Genes and Proteins

    In this study, we demonstrate that ​guanabenz protects oligodendrocytes both in vitro (in primary culture and cerebellar explants) and in vivo from ​IFN-γ-mediated death. ​Guanabenz also protects oligodendrocytes and ameliorates clinical symptoms in chronic EAE, with a concomitant decrease in the numbers of inflammatory ​CD4+ T cells within the CNS. Finally, treatment with ​guanabenz after development of clinical symptoms in relapsing-remitting EAE dampens the severity of the subsequent relapse. These data demonstrate the CNS-protective abilities during inflammation of an FDA-approved drug that enhances the ISR, a novel treatment strategy that may have potential as a therapeutic approach to treating MS.
    Last edited by Lazarus; 02-15-2016 at 04:18 AM.
    Linda~~~~

    Be the kind of woman that when your feet hit the floor each morning the devil says:"Oh Crap, She's up!"

  4. The following 5 users say "thanks"


  5. #3
    Distinguished Community Member SuzE-Q's Avatar
    Join Date
    Nov 2006
    Posts
    1,632

    Default

    I wonder if Gary has been on this already, it's a high blood pressure med?

    http://www.mayoclinic.org/drugs-supp...n/drg-20064106

    https://clinicaltrials.gov/ct2/show/NCT02423083

  6. The following 6 users say "thanks"


  7. #4
    Distinguished Community Member SalpalSally's Avatar
    Join Date
    Oct 2006
    Location
    SWOhio
    Posts
    3,569

    Default

    The words "Limited Ability"stand out like a sore thumb here
    and the other dirty word "Mice".

    oh well, they're working on It, at least!
    Last edited by SalpalSally; 02-15-2016 at 07:28 AM.
    Love, Sally


    "The best way out is always through". Robert Frost







  8. The following 4 users say "thanks"


  9. #5
    Distinguished Community Member
    Join Date
    Oct 2006
    Posts
    1,351

    Default

    No I haven't even heard of this one. There is another one called Lisinopril (an ACE inhibitor). I will bring this up to my Doc next week.

  10. The following 4 users say "thanks"


Similar Threads

  1. Abstract of study on low dose naltrexone
    By Lazarus in forum Multiple Sclerosis
    Replies: 14
    Last Post: 10-14-2017, 02:49 PM
  2. Replies: 17
    Last Post: 05-09-2015, 03:24 AM
  3. Abstract of a study if Ampyra
    By Lazarus in forum Multiple Sclerosis
    Replies: 1
    Last Post: 12-12-2014, 08:49 PM
  4. Replies: 3
    Last Post: 02-23-2013, 10:09 AM
  5. Age and disability accumulation in MS (PubMed abstract)
    By agate in forum Multiple Sclerosis
    Replies: 7
    Last Post: 09-17-2011, 04:55 PM

Posting Permissions

  • You may not post new threads
  • You may not post replies
  • You may not post attachments
  • You may not edit your posts
  •  


BTC Inc's Disclaimer and Privacy Policy

The material on this site is for information & support purposes only, and is not a substitute for medical advice provided by a licensed health care provider. Always consult your doctor before trying anything that you find online.