Thursday, 30 January 2014

The over-activated Immune System in Autism or “why has NAC stopped working?”

 Organs of the Immune System

 Today’s post will combine some first class science from MGH (Massachusetts General Hospital) with some feedback that I have been receiving.
I have been receiving comments from parents who have tried some of the various new scientifically-based drug therapies for autism.  For some parents, none of them work.  This is not a surprise, since we have established that “autism” is just a general term for a collection of behavioral symptoms.  These symptoms can be caused by a remarkable variety of different factors and so a therapy can only be successful, if it is matched to the appropriate subject.  The lack of biomarkers currently makes it a case of trial and error.
What really draws my attention is when a successful therapy appears to “stop working”.  This has already happened to my son and it just happened to a reader of this blog; “NAC has stopped working”.
So I applied myself to figuring this out.  In fact, it is quite simple.  Here again we can learn from the comorbidities.  Asthma is another, sometimes nasty, auto-immune inflammatory condition.  Asthma often has flare-ups, but they are often quite predictable - icy cold air in winter and pollen in summer.  Most asthma sufferers in developed countries are very well cared for, and their medication is varied according to the magnitude of their symptoms.  A severe asthma attack may result in a visit to the nearest hospital and treatment with potent steroids, but the science is well understood.
When well-targeted, the current autism drugs can work reasonably well in treating the autism of “stable” subjects; just as a low dose of inhaled corticosteroid usually controls my son’s asthma.  However, when an external factor comes along and over activates the immune system, the medication is overwhelmed.  In asthma you would hear wheezing and have to make frequent use of a “rescue” inhaler like Ventolin and if that was overwhelmed, it would be a case of a nebulizer or an oral steroid, at home, or in hospital.
Unfortunately, you cannot call your doctor and say “my autism drug has stopped working”; he would not believe it worked in the first place.
Having been able to treat autism, it is quite a shock to see all those gains evaporate.  Fortunately, help is at hand in the scientific literature.  In the case of Monty, aged 10 with ASD, the problem was caused by something as simple as pollen.  The pollen triggered the “degranulation” of so-called mast cells that released histamine, serotonin and a whole host of inflammatory cytokines into the blood.  This results in the immune system being in a state of “over-activation”.  This takes the body back to the days in which such over-activation caused the damage that led to the child’s autism.
If I had the resources of the Massachusetts General Hospital (MGH), I would simply establish a base-line of inflammatory markers, like IL-6, for each subject; then, when the subject’s drugs “stopped working” I would measure them again.
Having recently come across a clever Italian called Alessio Fasano, a doctor specialized in Celiac Disease at MGH; I would also test serum Zonulin levels.  Now, Zonulin may sound like something out of Star Trek, and it has only a tiny entry in Wikipedia, but it is possibly the holy grail for those involved in the Gluten and Casein free diet.
Zonulin is a protein that controls the permeability of the gut (digestive tract).  It is also measurable and is indeed a very good indicator of who has a “leaky gut”.  According to Fasano, a leaky gut is a precondition for autism.  No leaky gut, no autism possible.

Now you might be thinking that this talk of leaky guts will then lead me to make crazy claims linking the gut to the brain and then to autism.  Well I am not going to make any such claims; I will leave the highly respected doctor from MGH to do that for me.
There are two videos.  The autism one is over an hour long, but is only a couple of weeks old.  The alternative film is much shorter, but is talking more generally about auto immune diseases.

Then click on the film that looks like this:-


Or the short film:-


This is all very interesting and clearly permeability of the gut looks like a big factor in some people’s day-to-day autism.  It may very well also be a factor in those “flare-ups”, which cause the immune system to “cancel out” the effects of otherwise effective autism drugs.  You may have noted in some of the more shocking autism news stories, that can even end in murder/suicide, ulcerative colitis had developed in the intestines of the autistic person, leading to a severe deterioration in behaviour, that then became unbearable for the carers.

Dr Fasano is a gastroenterologist and so has a lot to tell us about the gut, but some other areas are also involved. We also have the leaky blood brain barrier, a factor in other diseases like MS; a biomarker for that would also be handy.  We also have all the work on mast cell degranulation from Theoharides.  It just has to be fitted together.
So my advice to anyone whose “NAC has stopped working” is to look at what has re-activated your child’s immune system.  It might be Seasonal Autistic Mastocytosis, but it might very well be a related to Fasano’s leaky gut or at the extreme, some kind of colitis (Dr W’s autistic enterocolitis, perhaps).

Perhaps some of those children who do not respond to any of the current autism drugs are in a chronic state of immune system over-activation.  For them, no drug can help, unless the immune system is first re-set. (pass the prednisone or even some TSO; more on immunomodulation here)


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