John’s Hopkins FAQs: The meaning of neuroinflammatory findings in autism

30 Nov

In their recent series on autism the Chicago Tribune exposed how a Johns Hopkins team’s findings of neuroinflammation have been misused to justify unproven autism treatments.

The Tribune included very short piece, Researchers warn against misusing report. The piece includes a link with some very valuable information, but it is unfortunately somewhat obscure. The web address they list (chicagotribune.com/autismstudy) is unlinked, and actually links through to the Hopkins team’s FAQ.

That FAQ is definitely worth reading and referring to when you read or hear “neuroinflammation”.

The FAQ is rather thorough, and I am in danger of just copying the entire thing here. Since I haven’t asked for permission, I’ll quote a small fraction of the FAQ. Yes, I am aware of the irony there–cherry picking information from this team is exactly what has led to the problems the Tribune reported upon. So I’ll say it again: go and read the FAQ for yourself.

Here is part of question 2:

Is neuroinflammation always present in the brain of autistic patients?

NOT necessarily. Since autism is a disorder that is highly variable in the ways it presents, and may be associated with multiple causes, it is possible that our sample of cases does not represent the entire autistic spectrum.

Here’s part of question

Are microglial and astroglial reactions always bad for the brain?

NO. The microglia and astroglia in the CNS may have a two-sided role in the inflammatory responses of the brain: they can act both as direct effectors of injury and on the other hand as protectors of the brain.

I’ll include all of question 12:

If there is neuroinflammation in the brain of some autistic patients, is treatment with anti-inflammatory or immunomodulatory medications indicated?

At present, THERE IS NO indication for using anti-inflammatory medications in patients with autism. Immunomodulatory or anti-inflammatory medications such as steroids (e.g. prednisone or methylprednisolone), immunosupressants (e.g. Azathioprine, methotrexate, cyclophosphamide) or modulators of immune reactions (e.g. intravenous immunoglobulins, IVIG) WOULD NOT HAVE a significant effect on neuroglial activation because these drugs work mostly on adaptive immunity by reducing the production of immunoglobulins, decreasing the production of T cells and limiting the infiltration of inflammatory cells into areas of tissue injury. Our study demonstrated NO EVIDENCE at all for these types of immune reactions. There are ongoing experimental studies to examine the effect of drugs that limit the activation of microglia and astrocytes, but their use in humans must await further evidence of their efficacy and safety

Capitals are in the original.

The Hopkins team is the source when it comes to neuroinflammation in autism. If they chose to write this FAQ and emphasize some points in all capitals, it’s well worth taking them seriously.

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7 Responses to “John’s Hopkins FAQs: The meaning of neuroinflammatory findings in autism”

  1. dr treg November 30, 2009 at 09:31 #

    There is often room for scepticism when scientists use the upper case for certain words or sentences in their reports/conclusions.
    Certainly other researchers apart from Johns Hopkins are looking at the effects of prednisolone and other immunosuppressants on regulatory T-cells and macrophages/dendritic cells/microglia in inflammatory diseases including autism often with conflicting results.
    http://www.jimmunol.org/cgi/content/abstract/183/2/841
    http://www.ingentaconnect.com/content/ben/cst/2009/00000004/00000003/art00006
    http://cjasn.asnjournals.org/cgi/content/abstract/4/10/1661
    Assistant Professor DeWitt`s study of TREGS in autism is awaited.
    http://www.ecu.edu/cs-dhs/pharmacology/DeWitt09.cfm

    Christina Hift M.D., F.A.A.P., Clinical Assistant Professor of Pediatrics at the Albert Einstein College of Medicine describes prednisone as appearing “to be one of the only medications that has a high rate of success in treating the underlying cause of speech loss or lack of speech in autism.”
    http://www.aheadwithautism.com/research.html
    There is uncertainty with regards the answer to the questions
    1. “Do TREGS control the microglial activity in inflammatory disorders such as autism” as there are few studies on this matter.
    http://www.abdserotec.com/animation/t-cell/
    2. “Can immunosuppressants such as prednisone lead to significant clinical improvement in autism?” as there are no double-blind controlled clinical trials of prednisone in autism.

    It is an old adage in medicine “never to say never” – especially in the upper case.

  2. passionlessDrone November 30, 2009 at 17:44 #

    Hi Dr. Treg –

    From Dr. DeWitts page:

    We believe that autoreactive T cells lead to neuronal damage and suspect that mast cells alter the permeability of the blood-brain barrier to allow infiltration of autoreactive T cells into the brain (we are working with Dr. Jared Brown to develop a mast cell project).

    This is a pretty interesting statement. Theoharides is pretty big on mast cell involvement with autism; in fact, he has a paper coming out in a month or so that shows extremely highly elevated rates of autism in a population with mastocytosis.

    I’d love to dig deep into this subject but don’t have the time now.

    – pD

  3. Mike Stanton November 30, 2009 at 22:47 #

    Dr Treg believes that

    There is often room for scepticism when scientists use the upper case for certain words or sentences in their reports/conclusions.

    and proceeds to capitalize Tregs!

    pD
    I am interested in the disclosure statement in an earlier paper by Theoharides detailing his patents.

    US patents No 6,624 148; 6,689 748; 6,984 667; 7,115 278; 10/811 825 and EPO 136577 (awarded to T.C.T.) cover methods and compositions for blocking mast-cell activation. These patents and the dietary formula NeuroProtek1, which could be used for autism, have been licensed to Algonot, LLC (www.algonot.com).

    Theoharides is a well qualified researcher with an impressive publication record. However very few of those publications are directly related to autism and those that are are literature reviews rather than clinical studies. Perhaps his new paper will remedy that. Even so, he does have a commercial interest in the success of this theory and I would like to see it supported by disinterested researchers.

  4. dr treg November 30, 2009 at 23:31 #

    Touche

  5. passionlessDrone December 1, 2009 at 02:11 #

    Hi Mike Stanton –

    Theoharides is a well qualified researcher with an impressive publication record. However very few of those publications are directly related to autism and those that are are literature reviews rather than clinical studies. Perhaps his new paper will remedy that. Even so, he does have a commercial interest in the success of this theory and I would like to see it supported by disinterested researchers.

    Very nice find and I agree with your assessment.

    It does seem that Theoharides has been studying his primary point of interest, mast cells, for over three decades. Damn, though, I didn’t know he had so many articles in Nature and Science! He claims a 1/10 prevalance of autism in his patients with mastocytosis.

    Here is a presentation by him regarding mast cells and autism. I got through about 1/3 of it earlier today.

    I have a lot of thoughts concerning activated microglia and the Hopkins FAQ that I’m trying to articulate well. Sorry for derailing the thread.

    – pD

  6. passionlessDrone January 17, 2010 at 16:02 #

    Hello friends –

    This paper, Autism spectrum disorders and mastocytosis. was published the other day and I thought I’d post a link as it was discussed here previously.

    Theoharides claims a roughly 1/10 prevalance of autism in patients with mastocytosis. I’ve yet to read the entire paper, but hope to soon.

    – pD

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