Friday, 27 February 2015

Causing MS by blockade of TNF

Napolitano M, Balato N, Ayala F, Cirillo T, Balato A. Multiple sclerosis following anti-tumor necrosis factor-alpha therapy for psoriasis: First case in Italy? Case report and review of the literature. G Ital Dermatol Venereol. 2015 Feb 18. [Epub ahead of print]

The use of Tumor Necrosis Factor alpha (TNF--α) antagonists has profoundly improved clinical management of psoriasis and other inflammatory diseases, but acute and chronic adverse reactions, including demyelination, are becoming increasingly recognized. We reported a case of multiple sclerosis in a 48--year--old Italian man with plaque psoriasis treated with etanercept. Through a literature review, we found a total of 35 psoriatic patients, including our case, in whom a demyelinating disease developed in course of TNF--α antagonists therapy. Since neurological disorders are rarely associated with the use of anti--TNF--α therapy in psoriatic patients, but have severe side effects, physicians should screen patients before starting therapy, excluding a positive anamnesis for demyelinating disease;; if patients receiving anti--TNF--α drugs develop new or unusual neurological symptoms, the anti--TNF--α drug should be stopped and patient should be properly examined. Furthermore, therapies for demyelinating diseases that could exacerbate psoriasis manifestations should be carefully avoided.

Tumor necrosis factor is a central mediator in inhibiting arthritis but if you inhibit TNF in MS it can make MS worse. In other conditions it can give you MS as shown in this study.

However in animals the jury is out and blocking TNF can do good things and it can do unwanted things,it depends on the context.

In animal studies mechanism of action is all important an in yesteryear (before they did the studies in MS) it was said TNF is bad so block it and there are a number of drugs that were claimed to inhibit TNF. However now this idea has been questioned and blockade of TNF can make MS worse so should we be using them in MS?

What do you think and what would you think if I said they are being tested in MS?

10 comments:

  1. If that's true that anti-TNF agents are being tested in MS then my reaction is one of horror. I wonder if whoever is proposing this has read the literature?

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  2. I think it is just a guess as to what it will do in human based on animal results. Until the cause is determined I don't know what the point is. Is there some indication that TNF is abnormal or not controlled well in MS or are studies being conducted as a result of EAE experience?

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  3. I read a few years ago about patients with psoriasis treated with etanercept may get a demyelinating disorder.

    There's this paper:
    Libyan J Med. 2007; 2(2): 99–102.
    Published online 2007 Jun 1. doi: 10.4176/070314
    PMCID: PMC3078281
    Central nervous system demyelination associated with etanercept in a 51 years old woman
    Wanis H Ibrahim,1 Mohammed Hammoudah,2 Naveed Akhtar,3 Hassan Al-Hail,3 and Dirk Deleu3

    My reaction too is of horror and I would not want to take this drug with my MS.

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  4. What is known about possible reasons of anti-TNF-alpha triggerred demyelianting disorders? Does it tell anything about MS triggers?

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    Replies
    1. It suggests that inflammation in the CNS is different to that in the periphery. Whether anti-TNF inducement of MS in RA or other patients patients is activation of previously silent MS or induction of new disease is at present unknown.This trial of an anti-TNF therapy in MSers from a while back significantly made things worse. Goes to show that as far as immune therapy goes, sometimes a one-size fits all approach doesn't work.
      http://www.ncbi.nlm.nih.gov/pubmed/10449104

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  5. How does biotin effect TNF alpha?

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    Replies
    1. I'm not sure if anything is known about any association between biotin and TNF, having just done a quick search on PubMed.

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    2. Biotin deficiency up-regulates TNF-α production in murine macrophages
      Toshinobu Kuroishi*,1, Yasuo Endo*, Koji Muramoto† and Shunji Sugawara*
      http://www.jleukbio.org/content/83/4/912.fullhttp://www.jleukbio.org/content/83/4/912.full

      These results indicate that biotin deficiency may up-regulate TNF-α production or that biotin excess down-regulates TNF-α production, suggesting that biotin status may influence inflammatory diseases.

      I was thinking that if MSers could be biotin deficient in spinal fluid (article I mentioned from 1999), then what is this doing to TNF?

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    3. So, biotin deficiency upregulates TNF alpha production, TNF alpha blockade can cause/reactivate MS, yet biotin is being touted as the wonder drug for MS.
      It's complicated isn't it?

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    4. From what I have read biotin doesn't help reduce relapses. But it may help improve the condition of progressive MSers or RR MSers symptoms after a relapse.

      I had a severe relapse due to stress and anxiety before I was diagnosed with MS or had any idea my illness was MS. It began as an infection. The vagus nerve controls the production of TNF which is useful with an infection but can be also triggered by anxiety. In my case it would seem there was over production of TNF.

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