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SANDESTIN, FLA. – Activated microglia may be a root cause of fibromyalgia, and bringing them back to a resting state an effective path to symptom relief.
Jarred Younger, PhD, is particularly interested in dextronaltrexone, the right-handed isomer of the drug commonly employed in addiction medicine, for calming microglia in fibromyalgia.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Unlike the commercially available levo-naltrexone, which binds at both the mu-opioid receptor and Toll-like receptor 4 (TLR4), dextronaltrexone blocks only TLR4. Blocking this receptor interferes with the cells’ ability to recruit peripheral immune cells, which may enter the brain, release cytokines, and induce a proinflammatory environment. By targeting only TLR4 and sparing opioid receptors, , Dr. Younger said in a video interview at the annual Congress of Clinical Rheumatology.
He already has investigated low-dose levo-naltrexone in a small positive crossover trial in 31 fibromyalgia patients. While taking the drug, patients reported significantly less pain and improved mood.
Dr. Younger also recently published a study suggesting that low-dose naltrexone actively improves peripheral proinflammatory cytokine levels.
The placebo-controlled crossover trial enrolled eight women with moderately severe fibromyalgia who took 4.5 mg naltrexone daily for 8 weeks. Compared with baseline, they had significantly reduced plasma levels of a variety of interleukin (IL) subtypes. Also reduced were interferon-alpha, transforming growth factor-alpha and -beta, TNF-alpha, and granulocyte-colony stimulating factor. Patients experienced a mean 15% reduction in fibromyalgia pain and an 18% reduction in overall symptoms.
But proving the drug’s method of action continues to be a challenge, he admitted. It’s not easy to observe microglial trafficking and cellular response to immune signaling in the brain.
Dr. Younger is preparing to launch an innovative PET study that should prove whether activated microglia are recruiting peripheral leukocytes into the brains of fibromyalgia patients. He intends to isolate T and B cells from blood, tag them with a PET radioligand, and reinject them into the subject.
“Since those cells are tagged, a few days later, we can scan the person and see if those cells made it into the brain,” Dr. Younger explained. “If we find T cells and B cells in the brain, that’s clear evidence that the peripheral immune system is attacking and infiltrating the brain, which would be very good in telling us what’s going on in fibromyalgia.”
Low-dose naltrexone is not approved for treating fibromyalgia, he noted. However, during the discussion period after Dr. Younger’s presentation, a number of physicians said they have been using the drug in fibromyalgia patients; some said it has been useful for patients with multiple sclerosis, as well.
Dr. Younger had no relevant financial disclosures.
SANDESTIN, FLA. – Activated microglia may be a root cause of fibromyalgia, and bringing them back to a resting state an effective path to symptom relief.
Jarred Younger, PhD, is particularly interested in dextronaltrexone, the right-handed isomer of the drug commonly employed in addiction medicine, for calming microglia in fibromyalgia.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Unlike the commercially available levo-naltrexone, which binds at both the mu-opioid receptor and Toll-like receptor 4 (TLR4), dextronaltrexone blocks only TLR4. Blocking this receptor interferes with the cells’ ability to recruit peripheral immune cells, which may enter the brain, release cytokines, and induce a proinflammatory environment. By targeting only TLR4 and sparing opioid receptors, , Dr. Younger said in a video interview at the annual Congress of Clinical Rheumatology.
He already has investigated low-dose levo-naltrexone in a small positive crossover trial in 31 fibromyalgia patients. While taking the drug, patients reported significantly less pain and improved mood.
Dr. Younger also recently published a study suggesting that low-dose naltrexone actively improves peripheral proinflammatory cytokine levels.
The placebo-controlled crossover trial enrolled eight women with moderately severe fibromyalgia who took 4.5 mg naltrexone daily for 8 weeks. Compared with baseline, they had significantly reduced plasma levels of a variety of interleukin (IL) subtypes. Also reduced were interferon-alpha, transforming growth factor-alpha and -beta, TNF-alpha, and granulocyte-colony stimulating factor. Patients experienced a mean 15% reduction in fibromyalgia pain and an 18% reduction in overall symptoms.
But proving the drug’s method of action continues to be a challenge, he admitted. It’s not easy to observe microglial trafficking and cellular response to immune signaling in the brain.
Dr. Younger is preparing to launch an innovative PET study that should prove whether activated microglia are recruiting peripheral leukocytes into the brains of fibromyalgia patients. He intends to isolate T and B cells from blood, tag them with a PET radioligand, and reinject them into the subject.
“Since those cells are tagged, a few days later, we can scan the person and see if those cells made it into the brain,” Dr. Younger explained. “If we find T cells and B cells in the brain, that’s clear evidence that the peripheral immune system is attacking and infiltrating the brain, which would be very good in telling us what’s going on in fibromyalgia.”
Low-dose naltrexone is not approved for treating fibromyalgia, he noted. However, during the discussion period after Dr. Younger’s presentation, a number of physicians said they have been using the drug in fibromyalgia patients; some said it has been useful for patients with multiple sclerosis, as well.
Dr. Younger had no relevant financial disclosures.
SANDESTIN, FLA. – Activated microglia may be a root cause of fibromyalgia, and bringing them back to a resting state an effective path to symptom relief.
Jarred Younger, PhD, is particularly interested in dextronaltrexone, the right-handed isomer of the drug commonly employed in addiction medicine, for calming microglia in fibromyalgia.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Unlike the commercially available levo-naltrexone, which binds at both the mu-opioid receptor and Toll-like receptor 4 (TLR4), dextronaltrexone blocks only TLR4. Blocking this receptor interferes with the cells’ ability to recruit peripheral immune cells, which may enter the brain, release cytokines, and induce a proinflammatory environment. By targeting only TLR4 and sparing opioid receptors, , Dr. Younger said in a video interview at the annual Congress of Clinical Rheumatology.
He already has investigated low-dose levo-naltrexone in a small positive crossover trial in 31 fibromyalgia patients. While taking the drug, patients reported significantly less pain and improved mood.
Dr. Younger also recently published a study suggesting that low-dose naltrexone actively improves peripheral proinflammatory cytokine levels.
The placebo-controlled crossover trial enrolled eight women with moderately severe fibromyalgia who took 4.5 mg naltrexone daily for 8 weeks. Compared with baseline, they had significantly reduced plasma levels of a variety of interleukin (IL) subtypes. Also reduced were interferon-alpha, transforming growth factor-alpha and -beta, TNF-alpha, and granulocyte-colony stimulating factor. Patients experienced a mean 15% reduction in fibromyalgia pain and an 18% reduction in overall symptoms.
But proving the drug’s method of action continues to be a challenge, he admitted. It’s not easy to observe microglial trafficking and cellular response to immune signaling in the brain.
Dr. Younger is preparing to launch an innovative PET study that should prove whether activated microglia are recruiting peripheral leukocytes into the brains of fibromyalgia patients. He intends to isolate T and B cells from blood, tag them with a PET radioligand, and reinject them into the subject.
“Since those cells are tagged, a few days later, we can scan the person and see if those cells made it into the brain,” Dr. Younger explained. “If we find T cells and B cells in the brain, that’s clear evidence that the peripheral immune system is attacking and infiltrating the brain, which would be very good in telling us what’s going on in fibromyalgia.”
Low-dose naltrexone is not approved for treating fibromyalgia, he noted. However, during the discussion period after Dr. Younger’s presentation, a number of physicians said they have been using the drug in fibromyalgia patients; some said it has been useful for patients with multiple sclerosis, as well.
Dr. Younger had no relevant financial disclosures.
REPORTING FROM CCR 2018