CSF miRNAs involved in FM

Discussion in 'News and Research' started by IanH, Oct 26, 2013.

  1. IanH

    IanH Active Member

    This is a very significant study for those with FM (whatever the origin of the FM, injury, ME/CFS or other sources)

    Generally miRNAs regulate cell metabolic processes through complicated mechanisms, including directly targeting key molecules (transporters or enzymes / kinases) of metabolic processes. MiRNAs can directly modulate the expression of metabolic transporters or enzyme activities. In addition, MiRNAs also play pivotal roles in the expression level of transcription factors.

    This study has found Six genes in particular that are malfunctioning (or possibly SNPs) resulting in low levels of the particular mi-RNA in response to need. These genes produce the mi-RNA's in the CSF. In the FM subjects the levels of mi-RNA were below that of normals under the circumstances normally stimulating the elevation of the mi-RNA.

    The most significant is miR-145 which correlates with pain and fatigue (This mi-RNA is also downregulated in endometriosis and ulcerative colitis but unlike in those illnesses it is not associated with insulin-like growth factor).

    The second key mi-RNA, miR-21. This is involved in glial and neuronal modulation after injurious pain as well as regulation of neuropathic pain. So where a person has spinal injury (even mild compression stress) this mi-RNA is important.

    Thirdly miR-29 is decreased in alzheimers, parkinsons and myotonic dystrophy. In an animal exercise study this mi-RNA was increased leading to improved cardiac function after exercise. So for FM the decrease in miR-29 can result in impaired cardiac function and slower cardiac improvement due to exercise. (This is what we have found, people with FM need to exercise but the exercise has much much slower benefit than for healthy people AND if they stop exercising their deterioration is faster.)

    Forthly miR-23b is a regulator of mu-opiod receptor expression. This is repressed in several auto-immune diseases such as MS, SLE and EAE. It is anti-inflammatory. Hence pain modulation is impaired.

    Fifthly, miR-195-5p is involved in energy metabolism and modulates mitochondrial function. It is also a direct regulator of GLUT3 and is associated with control of lactate production during elevated glycolysis.

    Lastly miR-223 when downregulated (as in FM) promotes TLR-triggered IL-6 and IL1b production. That is its downregulation or lowered levels promotes inflammation. Its upregulation in the nervous system protects neurons by targeting the glutamates receptors.

    http://www.plosone.org/article/info:doi/10.1371/journal.pone.0078762?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed: plosone/PLoSONE (PLOS ONE Alerts: New Articles)
    Last edited: Oct 26, 2013
  2. mbofov

    mbofov Member

    Interesting, Ian. I just skimmed it briefly, cannot absorb all the details but get a sense of what you're saying. Do you think this study will provide paths to treatment of FM?

    Mary
  3. IanH

    IanH Active Member

    Mary, treatment using this knoweldge about miRNA dysfunction is already being used in cancer treatment.
    There are three types of treatment:
    1. Where miRNA is downregulated an agonist drug is used to lift its production
    2. Where miRNA is upregulated as in some tumors an antagonist drug is used to reduce its production.
    3. miRNA replacement therapy where the miRNA is synthesised and injected into the relevant tissue. It is this latter form of treatment which may prove useful for FM and for ME/CFS. This replacement then drives or reactivates pathways which can lead to better function such as pain modulation eg reducing neurokinins such as substance P.

    In ME/CFS is is known that Natural killer cell function and maturation is disrupted. In this study miRNA is known to regulate NKC functions. eg as seen here:
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3584293/

    I believe the most important advances in ME/CFS will come from understanding how the miRNAs function and how to regulate them both by replacement therapy and epigenetically to form treatment.
  4. Mikie

    Mikie Moderator

    Thanks, Ian, as usual, you've brought us some very interesting, and relevant, material.

    Love, Mikie