Eradicate Microglia to treat autism? No. No and No.

12 May

Long ago I gave up on countering the misinformation that comes from the blog “The Age of Autism”. Not that there’s no value to it, but there is greater value for me in other tasks. Once in a while something that comes up that just needs to be taken on. In this case an article: Will Eradicating Microglia and Stopping Neuroinflammation Help in Autism?

Let me get to the conclusion quickly: No. Eradicating a whole class of cells in the brain is a bad idea. Not just because such a statement is obvious, but because there are already cases of children being harmed by people “treating” glial cell activation (neuroinflammation).

To say it again, “eradicating” microglia is dangerous, would cause harm and is just an incredibly bad proposition.

Micrioglial activation in autistic brains was discovered by Carlos Pardo and his group at John’s Hopkins. The seminal paper, Vargas et al., Neuroglial activation and neuroinflammation in the brain of patients with autism, was published in 2005. The authors knew that the understanding was incomplete at the time and that there was a great potential for people to jump ahead to “treat” neuroinflammation based on this report so they put a FAQ online. In it they state:

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.

Since then the understanding of the role of microglia has broadened. It has been shown that microglia play a role in brain development. At an IACC meeting last year, Carlos Pardo commented:

And that is important to point out because it was believed that microglia may have been the bad actor of the immune system in the brain, and actually, in the past 3 or 4 years, we are learning more and more about the beneficial effect and the normal biological function that microglia have on synaptic plasticity and synaptic formation.

And I want to point out this issue because it’s extremely important for brain development and plasticity, that manipulating the immune system with medication probably is not the best avenue for management of autism.

It’s a very understated comment, but on that should be heeded. Dr. Pardo has continued to work on the area of neuroninflammation and autism, including this clinical trial of a treatment.

Sadly, this isn’t just countering a very bad hypothetical question posed by irresponsible people at the Age of Autism blog. As I’ve already noted, “treating” microglial activation has already caused harm. Also, there’s a group claiming that all autism is caused by microglial activation and that the treatment is to “inhibit” microglial activation. The group calls itself “stop calling it autism”.

Autism is caused by a medical illness in which the brain’s immune system (microglia) attacks the connections in the brain. This leads to developmental delays that can cause significant social, communication and behavioral problems.

Our approach to treat autism and enable recovery is to inhibit microglial activation, which from evidence is known to destroy brain connections affecting brain development and function.

We at SCIA have designed and published a treatment protocol centered on this

They list elsewhere on their site:

Treatments include:
1. Antiviral medications
2. Antifungal medications
3. Antibiotics
4. Medications and supplements to increase natural killer cell activity
5. Immunoglobulin Therapy
6. Medications to inhibit microglial activation and to reduce nitric oxide levels

That’s a nice “shotgun” approach to a topic they clearly don’t understand.

In addition to the above, I’ve seen individuals and groups promoting NSAID’s (Non-steroidal anti-inflammatory drug), steroids, ACTOS (a potent diabetes treatment that has been shown to increase cancer risk)

Dr. Pardo is giving a talk at IMFAR this week, the title of which seems very on-point: Immunological Disarrangements in ASD Are Associated with Biological Processes and Homeostatic Mechanisms in ASD Rather Than Autoimmunity or Pathogenic Inflammation. “rather than…pathogenic inflammation”. The abstract is still embargoed, but it seems like the understanding is indeed moving forward. But away from the understanding that the Age of Autsim blog and “Stop Calling It Autism” are espousing.

This is an area where people have jumped ahead of the understanding and harm is being done.

By Matt Carey

Advertisements

4 Responses to “Eradicate Microglia to treat autism? No. No and No.”

  1. passionlessdrone May 12, 2014 at 20:21 #

    Interesting article.

    *If* altered microglial states in autism are playing a part in brain development, treating it *by the time you know the individual has autism* could be largely similar to closing the barn door after the horse has run out. The gestational and post natal contributions of glia to brain development are time dependent and largely (completely?) occur before we can (currently) say, ‘Y has autism’. Just stopping the activation of glia once those operations have been performed isn’t like having a time machine. What’s done is done.

    That being said, there are some studies that indicate that glia are interacting with synapses all the time, including some early work indicating participation in sensory integration functions (i.e., http://www.ncbi.nlm.nih.gov/pubmed/21072242 / http://www.ncbi.nlm.nih.gov/pubmed/21072242).

    I would also note that the small autism study was negative, a study on children with Fragile-X was positive [http://www.ncbi.nlm.nih.gov/pubmed/23572165]. Again, a small study. I’ve found myself wondering if the difference (if there is one and this isn’t noise) is a function of the degenerative nature of Fragile-X vs autism. I dunno.

    Immunological Disarrangements in ASD Are Associated with Biological Processes and Homeostatic Mechanisms in ASD Rather Than Autoimmunity or Pathogenic Inflammation

    Again, something here is possibly speaking to the difference between a degenerative disorder classically attributed to immune activation (i.e., alzheimers/ALS) and a disorder of delay / plateau.

    While somewhat old in terms of microglia research, http://www.ncbi.nlm.nih.gov/pubmed/22322212 is full/free and a good overview of data on how early life training / pheynotypic development of glia can shape the brain and ultimately, behavior.

  2. Science Mom May 13, 2014 at 02:22 #

    Why won’t these people leave their children alone; they are causing harm where none existed. Countering that foul drek on Age of Autism could be a full time job so I don’t blame you for steering clear but this is an important issue and they are clearly advocating, yet again, to use autistic children as guinea pigs. These sick freaks are the most vocal about “parental choice”, I can see why.

  3. reissd May 13, 2014 at 17:24 #

    Do I understand this correctly? They believe vaccines – after years of clinical trials in thousands and numerous studies – are not sufficiently proved safe, but are considering – even if only hypothetically, at this point – using a class of drugs that eradicate a type of brain cell on children even though it has not been tested for that in any way?

    • Sullivan (Matt Carey) May 13, 2014 at 17:34 #

      Pretty much. Except that I don’t think any of the available drugs will completely eradicate microglia.

      But on the other hand, there is a whole group pushing the idea of “treating” microglial activation even though it was made clear by the Hopkins group that with the data they had at the time (such understanding has since evolved) they couldn’t say if the activation was pathogenic, benign or beneficial.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

%d bloggers like this: