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Rapid improvement in severe long COVID following perispinal etanercept, 2022, Tobinick et al

Discussion in 'Long Covid research' started by Braganca, Jul 6, 2022.

  1. Braganca

    Braganca Senior Member (Voting Rights)


    This study aimed to describe the neurological improvements in a patient with severe long COVID brain dysfunction following perispinal etanercept administration. Perispinal administration of etanercept, a novel method designed to enhance its brain delivery via carriage in the cerebrospinal venous system, has previously been shown to reduce chronic neurological dysfunction after stroke. Etanercept is a recombinant biologic that is capable of ameliorating two components of neuroinflammation: microglial activation and the excess bioactivity of tumor necrosis factor (TNF), a proinflammatory cytokine that is a key neuromodulator in the brain. Optimal synaptic and brain network function require physiological levels of TNF. Neuroinflammation, including brain microglial activation and excess central TNF, can be a consequence of stroke or peripheral infection, including infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19.
    Trish, RedFox, livinglighter and 7 others like this.
  2. Creekside

    Creekside Senior Member (Voting Rights)

    I expect there would be plenty of volunteers from the ME community who would be willing to give this a try. If it doesn't help significantly, at least it would eliminate some theories.
    Hutan, alktipping, Binkie4 and 4 others like this.
  3. LarsSG

    LarsSG Senior Member (Voting Rights)

    Nancy Klimas is trialing Etanercept and Mifepristone in GWI, though presumably not with this special injection method.
  4. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

    London, UK
    I think etanercept has been tried in ME before with no useful effect.

    Perispinal administration sounds highly risky to me and unjustified in the absence of any evidence of inflammation.
    FMMM1, Lilas, Aroa and 5 others like this.
  5. Andy

    Andy Committee Member

    Hampshire, UK
    Tumor Necrosis Factor-alpha Inhibition Using Etanercept in Chronic Fatigue Syndrome

    "Recruitment Status : Terminated (After inclusion of four patients, two experienced moderate worsening of symptoms)"

    FMMM1, Starlight, Lilas and 13 others like this.
  6. BurnA

    BurnA Senior Member (Voting Rights)

    Aroa, Braganca and Peter Trewhitt like this.
  7. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

  8. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

  9. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

  10. Mister Person

    Mister Person Established Member (Voting Rights)

    Dude might be dodgy but his idea, is not so bad? Is mentioned similar in other places. Is it a good idea??? Good idea bad person.?

    From my layman's perspective, it seems he's guilty of the same things drug companies do, off label marketing?? A marketing problem.

    I'm glad somebody looked into before this, I was rather convinced though I noted the man held patents... And recognised conflict of interest. I wouldn't have ever found the quack watch stuff. Is he just overzealous, reckless, or a fraud?

    Okay a lil more reading and... The alzeheimers and neurological stuff is quack, but the stroke and pain could be legit! Can anybody with more knowledge help confirm

    I came across thinking of centrally administered anakinra, infliximab, canakinumab for fibromyalgia

    2 RCT if centrally administered etarnacept for pain

    https://pubmed.ncbi.nlm.nih.gov/24165696/ https://pubmed.ncbi.nlm.nih.gov/26243249/

    The use of cytokine inhibitors and glial modulators in clinical trials has shown some encouraging results. Intractable discogenic lower back pain patients showed up to 8 weeks of pain relief when given a single intradiscal treatment of entanercept, a TNF inhibitor 245. Additionally, lumbar disc herniation patients who received entanercept via transforaminal epidural injections had up to 26 weeks of pain relief following two injections in a randomized, double-blind, and placebo-controlled trial246. Another cytokine inhibitor, the IL-1 trap rilonacept, is well tolerated by patients, and in a proof-of-concept study, treatment with the drug showed pain relief for a small group of patients being treated for chronic refractory gouty arthritis247. By contrast, subcutaneous inhibition of IL-1β with anakinra has no beneficial effect on chronic fatigue syndrome CFS248. Microglial activation can be blocked in vitro by low doses of naltrexone 249, and a pilot trial also showed that treatment with the drug can help to reduce symptoms related to fibromyalgia.250.

    Therapeutics targeting IL-1β or the IL-1Ra have been proposed for a variety of pathologies, including autoinflammatory conditions, rheumatoid arthritis, and atherosclerosis, among others [91]. The FDA approved an anti-IL-1β monoclonal antibody (Canakinumab) to treat a spectrum of autoinflammatory syndromes known as cryopyrin-associated periodic syndromes (CAPS). More recently, clinical trials explored the ability of Canakinumab to protect against atherosclerotic disease (the CANTOS study). Interestingly, the results demonstrated that anti-IL-1β therapy via subcutaneous administration could prevent recurrence of cardiovascular disease while also protecting against arthritis, gout, and cancer [92]. Additionally, subcutaneous administration of an IL-1Ra (Anakinra) neutralizing antibody has shown promise for treating patients with rheumatoid arthritis, acute stroke, and autoinflammation-associated epilepsy syndrome [91, 93, 94]. Of note, both Canakinumab and Anakinra appear to be relatively well tolerated [91], and both achieve a reasonably high degree of bioavailability (75–92%) when administered subcutaneously [95, 96]. The mean terminal half-life of the two agents appears to differ considerably, with Canakinumab achieving approximately 26 days [95], compared to 4–6 h for Anakinra [96], although this may be quite different if administered directly into the CNS environment (e.g., intrathecal administration) for direct targeting of CNS nociceptors or glia. Given the promise of IL-1R/IL-1β antagonists/inhibitors in preclinical models of acute and chronic pain, testing whether Canakinumab or Anakinra can provide relief to patients suffering from severe chronic pain warrants investigation


    For stroke
    Last edited: Feb 23, 2023
    Peter Trewhitt likes this.

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