This blog is a way of sharing the information and resources that have helped me to recover my son Roo from an Autism Spectrum Disorder. What I have learned is to view our symptoms as the results of underlying biological cause, which can be identified and healed. I say "our symptoms" because I also have a neuro-immune disorder called Myalgic Encephalomyelitis.

And, of course, I am not a doctor (although I have been known to impersonate one while doing imaginative play with my son)- this is just our story and information that has been helpful or interesting to us. I hope it is helpful and interesting to you!

Friday, April 3, 2015

Mast Cells and the Brain with Dr Theoharides (and the autism connection)

This is an interview of Dr Theoharides about the connection between mast cell activation and autism, and specifically about the role of mast cells in the brain.  Dr Theoharides is a professor of pharmacology, internal medicine, and biochemistry at Tuft's University and the director of the Molecular Immuno-Pharmacology and Drug Discovery Laboratory there.  He has been researching mast cells and inflammation in the brain for over 20 years.  He has found that mast cells are one of the key regulators of the immune system, and has turned this interest on mast cell activation to loking at autism.

Brain Allergies And Autism - Dr. Theo Theoharides
From the blurb for the video on the BlogTalk site:

"Dr Theoharis Theoharides (Dr. Theo) from Tufts University, has come across a breakthrough in Autism.

Several years ago when Dr Theoharides was researching a completely different disease called Mastocytosis, he noticed an extremely high co- occurrence of Autism in these people. Through a simple survey it was found that 10% of people with Mastocytosis also had an ASD diagnosis. That raised a big red flag to Dr. Theo since having that big of an increase of having a disease within a certain population ( 1 in 10 for Mastocytosys) compared to the regular population (1 in a 100) points to a direct connection. This compelled Dr. Theo to do testing of autistic children and lead to the discovery that autistic children had activated Mast cells. "

Is there a subset of autism where there is an allergy to the brain?

Genetics cause about 5% of the cases of autism, so other factors need to be considered too.  1 in 10 children with Mastocytosis has autism, which is much higher than the rate in the general population, which does suggest a subgroup of people with autism.  Many children with autism also have true allergies to foods and environmental factors.

What are mast cells?

They originate in the bone marrow and go to every tissue in the body, they do not circulate as other white blood cells do.  They are found in the brain even though the brain does not have classic allergic reactions, which raises the question of what their role in the brain is?  Mast cells contain and release about 100 different chemicals.  Histamine is the only one we know how to deal with much, after it's been released.  We don't know what many of these other chemicals do in the brain.

What is the difference between an allergy and an intolerance?

In true allergy we measure IgE- the levels in the blood, but also specific IgE to specific allergens.  This blood testing can be used to direct skin prick testing to confirm the allergies.  Mast cells can be triggered by at least 50 other triggers in addition to IgE.  Wasp stings, antibiotics, mold and mold mycotoxins, can trigger the mast cells directly without involving IgE and will not test allergic to these things.  There is no quantitative measure of food intolerances.  IgG testing can reveal some of these intolerances.  He says that IgG allergies that are all the way to the right (have the highest degree of reaction) tend to be real allergies.  About 30% of kids on the spectrum have auto-antibodies to their own brains.  There will be a commercial test within the year to look for these antibodies.  The only symptom closely associated with these auto-antibodies is allergic reactions.

Does the presence of auto-antibodies make autism an auto-immune disease?

Many people have been talking about dysfunctional immunity in autism, so that topic is not new, but his team is the first to show where it may come from.  The medical definition for auto-immunity is the presence of ANA (anti-nuclear antibodies) in the blood.  Since this is not necessarily the case with autism or mast cell disease, they have been calling it an auto-inflammatory disease.  Then it was decided that a disease is "auto-inflammatory" if it involves dysfunction of Interleukin 1.  The brain does not have circulating white blood cells, instead it has a type of cell called a microglia.  Mast cells regulate the microglia, so when they get activated and fire they "turn on" the microglia, which then release their own inflammatory molecules and also start to proliferate so that they crowd out the connections between neurons, the way weeds can choke off plants in the garden.  A recent study of post-mortem brain tissue from people with autism found microglial activation in every sample.  At this point it is not clear what to call autism and mast cell disease as immune-related diseases.

At this point the interviewer mentions that her daughter was seen by Dr Zimmerman, who has done a lot of work on brain inflammation.  Her daughter (with PANDAS) has no symptoms of disorder when she has a fever.  Dr Z said it has to do with cytokines.  Since fever is regulated by mast cells, this suggests a connection.  Dr Theoharides says that many other people with autism do more poorly when feverish, so it is unclear why fever affects different people differently.  One concern is that fever opens up the blood-brain-barrier which would allow immune cells to go in.  A fever of 39 Celsius makes mast cells stop firing.

How do patients present?  What can you look for?

Brain fog is a very common symptom- brain fog includes poor attention, poor short-term memory, loss of words.  This is due to the microglia and the mast cells releasing chemicals that interrupt information processing.  Many patients with brain fog do very well on NeuroProtek, a supplement that can stabilize mast cells in the brain.

How do mast cell release affects different parts of the brain?  

Most of the mast cells in the brain are found in the hypothalamus, especially the part that connects the hypothalamus with the pituitary gland.  When mast cells trigger this area they trigger fight/flight, and are known to affect behavior.  Histamine is one of the primary molecules involved.  It promotes alertness, memory, consolidation of memories, and motivation.  If levels rise beyond a certain level it causes brain fog.  So we need some histamine, within a certain range.  Histamine can also come from bad bacteria and some foods.

Histamine can cause pain when it gets into connective tissue; people with Fibromyalgia often have mast cell disease, and many autism moms have Fibromyalgia.  Many mast cells in the brain sit directly on nerves and can cause nerve damage, called focal allergies, which can affect language and communication.  Mast cells are also prevalent in Broca's Area of the brain, a region important for language, as well as the hypothalamus, which helps to regulate emotions.  So focal allergies means that functions such as language and behavior are affected, as opposed to say the motor deficits seen in MS.  Mast cells release tryptase, an enzyme which is basically a meat tenderizer, when it is released it can damage the brain.

The question is how do these chemicals get into the brain, since many are thought to not cross the blood-brain-barrier?  Maybe they originate there, like CRH (corticotropin releasing hormone) being released in response to stress.  Neurotensin and CRH have been found to be very high in kids on the spectrum...and the two together have synergistic activity (meaning that when they are together they magnify each other's affects).  The two together also activate the microglia.  Autism is not just a psychiatric disease, the immune system is definitely involved.  Stress is a huge trigger.

How big is the subset in autism?  How do parents know if this is an issue for their child?

Allergists don't get it so they are not much help.  Up to 60% of kids with autism have "allergic-like" symptoms, so this could possibly be a very large group.  Watch a child's behavior and symptoms, see what is going on when the symptoms become worse.  Physical symptoms can include flushing and swelling.  Triggers other than classic allergens can include odors and chemicals such as perfume, weather changes, and even being over-stimulated with sensory input which causes stress.  A lot of these reactions are considered to be sensory issues, but this is the biology of "why".  Reactions can be delayed which can make identifying the trigger very hard.  Parents have to be detectives.  A study of over 97,000 kids with eczema found that over 20% also had ADHD and autism, which is a much higher percent than the general population.  Since autism can't cause eczema, the correlation or causality must go the other way.  Some herbicides trigger mast cells can can't be washed off and correlation has been found with eczema and herbicides.  If the mother has allergies or an auto-immune disease like psoriasis during pregnancy , the chances of her child having autism are 4 to 6 times higher.  It creates a susceptibility in the child so that they get sick when exposed to triggers outside the womb.

Dr Theoharides was just awarded a patent for diagnosing and treating autism.  This doesn't mean that the test or treatment are ready yet, rather that they are on the right track and can seek more funding to follow this trail.  NeuroProtek is just the beginning.  They have found a new molecule that increases BDNF (brain-derived neurotropic factor) which blocks microglia and protects neurons.  It may take about a year to get it to market.  Medications often have fillers and need meds compounded.  He says there is definitely hope in the future, there is also a lot that can be done now to reduce allergic symptoms.  Certain heavy metals, especially cadmium and aluminum, have a large role in triggering mast cells.  Kids should be looked at for metals because they can be detoxified.

These are his 2 non-profit sites, and have more info about the patents:

His main webiste is:

There are also many videos of him on YouTube, including these:
"Brain Allergy" and ASD
Presentation by Dr. Theoharides - Inflammatory Conditions
Dr. Theoharis Theoharides at Autism Canada
Polly meets Theoharis Theoharides (this focuses on brain inflammation and autism)