Chemical that Stimulates Estrogen Receptors Seen to Promote Myelin Repair Through ‘Good’ Inflammation in Mouse MS Model

Chemical that Stimulates Estrogen Receptors Seen to Promote Myelin Repair Through ‘Good’ Inflammation in Mouse MS Model

A chemical compound called indazole chloride promotes repair of myelin, the protective layer of nerve fibers, through “beneficial” inflammation in a mouse model of multiple sclerosis (MS), a study reports.

The preclinical research, “Increase in chemokine CXCL1 by ERβ ligand treatment is a key mediator in promoting axon myelination,” was published in the journal Proceedings of the National Academy of Sciences.

Current treatments for MS are not able to repair the damage to nerve fibers and myelin, both characteristic features of MS that lead to the symptoms marking this disease.

In the brain and spinal cord, myelin is formed by cells called oligodendrocytes after they mature from precursor cells. In contrast to healthy individuals, whose nervous system is able to regenerate damaged myelin, patients with MS cannot and such damage is permanent.

Prior work in mice with MS has shown that indazole chloride, a synthetic chemical that binds to and stimulates the estrogen receptor ERβ, improves motor function, promotes remyelination, and eases inflammation.

Now, scientists at University of California, Riverside found that indazole chloride’s effect on remyelination correlates with increased levels of CXCL1 in the periphery and in astrocytes, a cell of the central nervous system (CNS).

CXCL1 is a type of small molecule called a cytokine with a key role in inflammation. It binds to CXCR2 in oligodendrocytes, and as such is implicated in myelination.

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The investigators also observed that the extensive remyelination was accompanied by immune cells accumulating in the CNS.

While inflammation is damaging in autoimmune diseases, they noted it can also be beneficial — inflammation is required to fight infections and speed wound healing. Their findings suggest that indazole chloride promotes “good” inflammation, protecting oligodendrocytes while they remyelinate.

“Our data show that ERβ ligand neuroprotection/remyelination may be partly mediated by skewing the proinflammatory phenotype to a protective phenotype,” the researchers wrote.

“Indazole chloride and similar drugs may represent a promising new avenue of treating the underlying loss of myelin in [MS],” Seema Tiwari-Woodruff, PhD, the study’s senior author, said in a press release.

“With remyelination of axons, nerve impulses travel faster than before, thus decreasing multiple sclerosis disability. As a potential therapy for the treatment of multiple sclerosis, indazole chloride may represent the first in a novel class of drugs capable of reducing disability burden in patients with multiple sclerosis” Tiwari-Woodruff added.

The team considers indazole chloride an attractive compound because it does not cause the side effects of estrogen therapy. As ERβ receptors are present in other types of CNS cells beyond oligodendrocytes, as well as in immune T-cells, the scientists believe that indazole chloride may benefit not just MS patients, but also those with other autoimmune diseases.

Molecules chemically similar to indazole chloride are now being screened for potential testing in patients.

“It’s quite possible we may find an analog far superior to indazole chloride,” Tiwari-Woodruff concluded.

37 comments

  1. Roman Ksh says:

    Sign me up for it too. I need to speed up remyelination of my left hemisphere to reduce my right leg fatigue after 10 mins of running.

    • Karen G. says:

      You can still run? Walk too?You are very fortunate. Savour your abilities. Appreciate everything you can still do. Let’s hope new trials will help us all to prevent further damage and repair current damage.

      • Mari says:

        I so agree Retiring in 12 days. 30 years, hs teacher. Use scooter. I can barely walk. Hope trial comes to CT. Sign me up. 😘🙏

  2. Shawn Holloway says:

    I’m very interested and I’m more than willing to try. I was diagnosed with Primary Progressive in July 2017 and it has completely put a halt on my life and I’m knocking on the door of being confined to a wheelchair. I do everything that I am able to do to fight it, but with every punch I throw….it hits me with 5 more from every direction possible.

  3. Marian says:

    I believe menopause and the reduction in estrogen production definitely contributed to the decline in nerve impulses and disability from my MS.

  4. Chandan Jot Kaur says:

    I’m having SPMS since 2017 and treated by the best Neurologists Team of India.
    Have blagger/bowel incontinence and barely stand.
    Wish my doctor’s in India help me with this trial.

  5. Shirley Nemetz says:

    I would love to try Indazole Chloride for loss of myelin. I was diagnosed with MS 18 years ago I can’t walk good, very painful feet & legs at night, balance is awful. I’m on Ocrevus. PLEASE PUT ME ON THE TRIAL!!!!!

    • Jaimie says:

      How many infusions ofOcrevus have you had? I also have SPMS and just had my 2nd half of Ocrevus. Have you felt any differently? Thanks. Good Luck all🙏

      • John says:

        I am considering Ocrevus but have some reservations about it’s efficiacy relative to the possible side effects. Have you noticed any improvement? Thanks.

  6. Brenda Sierer says:

    This started with mice in 2014? If this study is are available for people, I would be so greatful to be a part of it. I have SPMS,Systemic Lupas and Sjogrens,diagnosed in 2003.
    Cheers,
    Brenda

  7. Helene Patterson says:

    I have had MS for 25 years, relapsing remitting, in the last four years I am at primary progressive. I cannot walk with out a device and long distant walking is obsolete, I need a scooter. I am 54 and would love a chance to be in a study for this trial. I have tried everything. Sad I get very angry that there is no help for MS patients with PPMS.

  8. Clare says:

    All the best to everyone!!! As cancer is treated with estrogen reducing drugs, I wonder if this would be available to those on these drugs who might develop MS in the process of treating their cancer.

    • Gail Bacon says:

      I was treated with Arimidex (estrogen reducing drug) and within 14 months of starting the drug, the early signs of PPMS started to show. Took another 5 years to get a diagnosis. Could the Arimidex have been a contributor to destroying my myelin? Just wondering

  9. Judy Epstein says:

    Dear indazole chloride scientists,
    PLEASE include us all in the clinical trial! I too since menopause have experienced slow downhill degradation. Thank you in advance!!! 🤩🤨🙄 🤐😏

  10. Ian S says:

    I would love to try this. I was diagnosed in April 2017 and medically retired in October 2017. I changed my diet to a vegan diet and feel great for doing so. I have PPMS so no meds to help/assist me. I have no pain or discomfort and I am thankful. The only trouble that I face now is with balance/gait. Remyelination seems to be not a cure but an improvement in function. If you need people to try it…I’m in (After everyone else on here). I wish all M&S sufferers the very best.

  11. Ian S says:

    I would love to try this. I was diagnosed in April 2017 and medically retired in October 2017. I changed my diet to a vegan diet and feel great for doing so. I have PPMS so no meds to help/assist me. I have no pain or discomfort and I am thankful. The only trouble that I face now is with balance/gait. Remyelination seems to be not a cure but an improvement in function. If you need people to try it…I’m in (After everyone else on here). I wish all MS sufferers the very best.

  12. I would love to take part of this trial in humans…have had MS for 31 years with RRMS for the first 26 years and have now SPMS. I’m still mobile but I can feel the ability lessening.

  13. Niveen Ramani says:

    Want to be a part of the trial as sadly not much help is available in India. Plz do let me know if i can be helped in anyway.

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