Discovering Dr. Theo

How I learned that Mast cells can cause Autism and possible new treatments

The best discoveries are often found completely by accident. It seems that may be happening again for Autism in a way.
One Doctor, Theoharis Theoharides (Dr. Theo) from Tufts University, has come across a breakthrough in Autism detection, diagnosis, and quite possibly a treatment. He is also working on a drug to prevent, reduce or even reverse autism. Sound too good to be true, well his research is backed up by hundereds of medical papers and medical evidence from not just him but other researchers at prestigious institutions around the world. Not to mention a mountain of parent testimonials. In this article I will describe his findings in a less scientific terminology loaded manner, think of it as "Mast Cells for Dummies". There are some sub pages that go into more details on some ofthe subjects for those wanting more information.

This all started four years ago when Dr Theo was researching a completely different disease called Mastocytosis, a rare intestinal disease, and noticed an extremely high 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. This I personaly feel gave him some credance since he discovered somthing he was not looking for.

Now a link between Mastocytosis and Autism would not mean much to most doctors never mind parents and activated mast cells even less so. To Dr. Theo this ment a lot. He knew that activated mast cells cause symptoms that will seem very familiar to most parents of autistic children such as;
  • allergic symptoms that alergist say are not alergies
  • intestinal inflammation
  • intestinal slowdown possibly resulting in distention
  • breakdown of the gut-blood barrier, i.e. leak-gut
  • high fevers and redslotchy hives
  • breakdown of the blood-brain barrier
  • brain inflamation
  • neurotoxins in the brain
  • reduced neural connectivity
  • "brain fog"
  • pain insesitivity
  • reduced learning ability
  • seizures
  • and even more
To top it off, This chain reaction involving mast cell activation can be triggered by a number of ways, from oxidative stress (enviromental), mercury, vacines (possibly thimerasol, but there is another source that fits even better!), geneics (damage/mutation), even prenatal extreme stress events. It is an amazing match to what parents see and report.

If you would rather start with some videos of Dr Theoharides talking about his finding rather then diving in deep, there are a few listed on the Videos page. I would recomend listening to Theoharides Disruption of the Gut-Blood-Brain Barrier & Autism to start. This is a 4 part series of an interview with Dr. Theo where he describes his findings.

A lucky encounter

I first heard of Dr. Theo at the 2010 National Autism Association conference, at the time my daughter was almost 4 years old (3 years effected and 2 years diagnosed) we had tried many things, and had seen few big successes. The Gluten/Casein/Soy-Free diet worked very well, but most supplements and therapies did not help much if at all. My wife Julie and I had been researching over the previous two years, it did take me longer to start, and we were very frustrated at the slow progress even after all these therapies, supplements and treatments. After such big successes from the diet, food testing, and Neurotherapy (Neurofield in particular) all we were left with was a slow progress from the many therapies Sophia was in and felt she was slowly falling father and father behind. I felt that something was missing, that there was some underlying medical process continuing that was keeping her locked away.
 
For this reason, and that it was close to us, we decided to attend the NAA conference with the hope that we could find the next therapy, treatment, or medical treatment that would help.When we registered for the NAA Conference they handed out presentation material and I went through all of it to find out which talks were on any new research. I felt I got a good understanding of what most the speakers were going over, except this on that was on something called Mast cells by someone whose name I did not know how to pronounce. The handed out presentation material on that presentation seemed somewhat confusing in that it had references to about everything; allergies, the gut, the brain, cellular reaction, mercury. This peeked my interest and I put it on the list of talks to go to.

What did I just get into

By the time I came to Dr. Theo’s talk, I had been to several others and felt I was keeping up quite well, I do have multiple science degrees. Then Dr. Theo started. I immediately knew this was different. The technical scientific detail was way beyond any other talk and I was struggling, badly, to keep up. He was presenting results from true double blind studies with control groups, referencing dozens of medical papers, describing research and many tests that explained everything I had been seeing with my daughter. The amount of research he was presenting felt to be more than the rest of the conference together. At the end of the talk I was writing feverishly and was almost numb, but knew I had stumbled across just what I was looking for.

Dr Theo had just described, and show through lab tests, how mast cells can become “activated” and start a chain reaction of events starting with intestinal problems and resulting in full blown autism. It even explained the great variety of causes of Autism; these cells are sensitive to the buildup of oxidative stress from environmental sources. This could be from any number of sources from drugs to PCBs to mercury, explaining how autism could be triggered by vaccines or how a child who was never vaccinated could get autism.
 
Mast cell what?
So what does this mean, what is a mast cell, what is activation? Well mast cells are typically associated with allergies where they histamines that make people sneeze, get hives, and all those other wonderful allergic reactions. These cells are actually the regulators of inflammation and are one of the immune system first lines of defense. When they are triggered an immune response is started, the mast cell even direct white blood cells where to go. Mast cells release molecules selectively depending on how they are triggered, whether in an allergic reaction or some other immune response.

Figure 4 - Mast Cell releasing Granules due to IgE (allergic) response

The Image to the left showa a mast cell releasing granules (bunches of molecules) in response to an IgE (regular allergy) response. The IgE response is on the bottom right and the granules are the round specled things inside the cell. The one on the left side of the cell is being released. Mast cells are filled with these granules and each granule contains dozens of molecules (the speckles) used in these reactions. Think of a basketball filled with baseballs that are filled with marbles. There is a long list of different molecules in these globules to do things such as; attract White Blood cell, make blood vessels permeable, cause inflammation, and much more.
 

Dr Theo had discovered that if Mast cells are exposed to enough oxidative stress they can be activated. Once a mast cell is activated it can “degranulate”, meaning it releasing all those molecules, the “marbles”, all at once, like an explosion. Now that the molecules (marbles) are not contained in the cell, and were not released in a globule (basketball), they all start working at once. The big problem here is that there are a lot of different molecules including some nasty ones that are neurotoxins, inflamatory, vasoactive, and one that is even a meat tenderizer. Yes, a meat tenderizer. It was also found that Mast cells do not have to fully degranulate, that certain triggers can cause the mast cells to selectively release molecules that can continue the path to autism if other cellular mechanisms go wrong

The gut I can understand, think poop.

Dr Theo went on to talk about how some of the molecules released by the mast cells were vasoactive, meaning they make the blood vessels more permeable, such as triptase, VEGF, and VIP to name a few. VEGF in particular was mentioned since a study done by several groups has shown that thimerisol causes mast cells to release the vasoactive molecule VEGF. As mentioned before these vasoactive molecules are there to let white blood cells through the blood vessel walls, but it will also let though other large molecules. This is meant to be done in a specific targeted area, but when the mast cells get activated this starts happening all throughout the gut, causing massive inflammation and making the blood vessels more permeable.

Figure 2 – Results from a study showing the effect of thimerosal on VEGF release from mast cells. At levels found in vaccines (10uM) VEGF is released at 10 times the normal level. The reduction at even greater levels (100 uM) is due to the mast cells dying not from a reduced release,

Well permeable blood vessels would be the definition of the breakdown of the gut-blood barrier. I say the gut-blood barrier since, the skin and the gut would be the first line of defense for the immune system and the gut is much more sensitive than the skin. The skin is meant to keep almost everything out and the gut is there to absorb, so exposure to any oxidative stress (chemicals, heavy metals, PCBs, etc) would affect the gut much more and faster. So any reaction to oxidative stress would most likely start off in the gut. I say most likely since I have learned that there can be exceptions, such as if a pregnant mother was exposed to a very stressful event or a sustained skin exposure on a child. For now I am going to stick with the gut disruption since that is what I first learned about and in any case the end reactions are the same just in a slightly different order.
When the presentation was talking about gut blood barrier breakdown I started to get excited. I knew my daughter had problems with this. She had not had normal stool in two years, obviously pointing to an intestinal breakdown. We had done yeast die offs and several suplements and special diets, but still the smelly mashed potatoe poo. If he had figured out the reason for this breakdown maybe he knew how to cure my daughter’s diarrhea and other intestinal problem. That would be worth it on it's own I thought and I don't change half the diapers, my wife would be elated.

Neuro what ... this is starting to sound hard

Dr. Theo then started talking about results from several lab tests where this molecule called Neurotensin was found to be high in the blood of many autistic children, about twice as high on average. So what does this mean, well I found out how neurotensin is an important regulatory molecule in the body and has an effect on may body functions that autistic children have problems with.  A few of these are, brain nerve communication (white mater), intestine muscle function, learning reward system (dopamine), hormone (testosterone and estrogen) regulation, coordination control, pain relief, and scoial/psycological functions to name a few. Do any of those sound familiar? It sure seemed to be a list of things wrong with my child.

I noticed that not all the samples from autistic children in this study had really high levels, but there was more to come later on where other levels were high in those children.

Dr. Theo had been looking for neurotensin since that was also seen in the people with Mastosytosis. Neurotensin is part of a family of molecules called neuropeptides (the name doesn’t matter too much, but think of a string of amino acids). This molecule neurotensin is from the mast cell and is normally used in the gut to relax muscles and work on the vagal nerve (I will come back to the vagal nerve later if you are not familiar with it, but it has been seen as being involved in autism for a long time).
Figure 3 - Test results showing neurotensin levels in the blood of typical children (Control A and B) and at n elevated level for most autistic children.

This topic on neurotensin went on to describe how once there has been a disruption to the gut-blood barrier neurotensin can get into the blood stream and sent to the rest of the body, as shown by elevated levels in the blood test of autistic children, see figure 3. The issue is that neurotensin also has the attribute that it can activate, or assist in activating, mast cells, so once neurotensin is in the blood stream it can trigger the mast cells throughout the body starting a chain reaction.

Damn my allergies are acting up

So now we have the mast cells in the gut being activated from oxidative stress and releasing molecules that break down the gut blood barrier and get into the blood stream where neurotensin and any oxidative stress hormones can trigger mast cells all throughout the body. This can show as allergic symptoms since many of the molecules the mast cells release are used in allergy response. One of the issues most parents of autistic children have is allergic symptoms that allergists cannot diagnose as allergies. This reaction can explain this perfectly since the mast cells are not triggered by a normal IgE response. there is not the focused skin reaction that a typical allergic reaction would see and in a blood test they do not see the IgE response or see the “Granules” (remember the description of the mast cell, these would be the baseballs) so they say it is not an allergy.  

Read this part twice, it is Money

Not only does mast cell activation explain allergies that are not allergies, but gives something extra to look for, by using a different testing method this can be detected. There is actually a new medical diagnosis for this called Mast Cell Activation Syndrome1,2 (MCAS). More information on the diagnosis and treatment can be found on the Journal of Hematology at http://www.jhoonline.org/content/4/1/10 or at the National Institute of Health at http://www.ncbi.nlm.nih.gov/pubmed/21035176. I prefer the Journal of hemeotology, it is easier to read.
MCAS is a new diagnosis so most doctors are not aware of it, but by providing them the information reference a doctor can diagnose this as a medical condition instead of just “crazy mom syndrome”. What is even more exciting is that there is a CPT code for this. Any Doctor can look up MCAS and test for it and then get it covered by insurance (CPT code). In addition to insurance coverage for the medical treatment, MCAS’s description is a medical condition with psychological effects, so some insurance companies will pay for therapies under MCAS’c CPT code since it is a medical condition.

When I heard that part, I was amazed. Someone had finally figure out what causes the gut-blood barrier breakdown and those ghost allergic symptoms, AND there was a new CPT code to beat the insurance companies with. I remember the early days of Autism when my daughter would get these hives or red splotches all over and all the doctors would say is, “its viral”. That seemed to be there fallback excuse to use instead of “I have no idea at all”. Then the insurance companies would say oh we don’t cover behavioral therapies. Of course with all the diet changes and supplements my daughter would probably come up negative on the test. For a fleeting second I thought, what if I let my daughter regress to get this diagnosis, but then I realized the divorce that would cause might cost more than the savings on therapies. This was still a breakthrough in itself I thought, but Dr. Theo went on with more and I sat there stunned and overwhelmed as I realized he was just at the start of describing a horrible chain reaction.

What about the Brain?

So we now know how those alergic symptoms start, but what about all the behavioral, emotional and speach issues that are seen in autism, something is going on in the brain. How could all this nasty neurotensin get into the brain. There is that Blood-Brain barrier that keeps amlost everything out. For neurotensin or, almost anything, to get into the brain, the blood brain barrier would have to be broken down and probably kept open for the damage to continue.
 
So Dr. Theo started showing pictures of the mast cells in the brain. They are normally located next to blood vessels, hugging the blood vessels in the brain as shown in the picture to the right (right side). This makes sense since mast cells are one of the first lines of defense and they work with the blood brain barrier to protect the brain in an immune response. It turns out this placement of the mast cells has a lot to do with the breakdown of the blood-brain barrier.
 
The blood brain barrier is a very tough one, letting almost nothing through except tiny molecules like simple sugars and amino acids. Once the mast cells are activated in the body there are vasoactive molecules released, neutotensin and other molecules in the blood stream passing through the brain where these mast cells “hugging” the blood vessels. A slight breakdown of the blood –brain barrier will allow the neurotensin to activate the mast cells in the brain releasing more neurotensin in the brain and other vasoactive molecules and this starting the whole chain reaction and leading to autism. Neurotensin is a neuropeptide (remember that name does not really mater no non doctors) and is a neurotoxin (yes anything with toxin in its name is bad) and it can trigger nerve cells to fire erratically. The mast cells secreting neurotensin would have to be near nerves in the brain to really have an effect. Well the picture to the right, side A (left side) shows where mast cells are in the brain, near blood vessels and nerves.
 

At this point in the presentation I started having trouble keeping up, there were all these test results and many published medical papers written by several different doctors from big name universities that were backing this all this research. I started to feel like there had been a major step toward the whole autism mechanism, What other process with this massive amount of evidence could better explain what  had been seeing. Yet still Dr. Theo kept going like the energizer bunny.

Hey, that sounds like something out of a zombie movie

He also mentioned that Tumor Necrosis Factor alpha (TNF)  was also one of the molecules released from mast cells, in fact mast cells are the only cells in the body that store TNF-α. Now the name should arouse some concern, not from the tumor part but the necrosis (as in death) part. TNF-alpha is normally used to cause inflammation, cell death, sepsis, fever, and viral replication. I thought now that is something that would go great inside my brain, well if I wanted to get brain inflammation a fever and nerve death. 
 
TNF-alpha is there for a reason, to kill viruses and tumors. Things that should not be in the body, nut man do you not want it wandering around in the brain. TNF-alpha itself is implicated in several diseases including inflammatory bowel disease, major depression, and Alzheimer’s. I also learned that TNF-alpha has other effect like making nerve synapses slow down. The combination of neurotensin and TNF-α would makes nerves fire erratically and not communicate well (sound familiar yet). Then yet another shoe fell and knocked me over.
Remember that neurotensin stuff that is now in the brain. Guess where the largest amounts of receptors for neurotensin are located; this would be what part of the body is most affected by high or low levels of neurotensis (this one made my jaw drop). They are in the diencephalon in the brain stem that controls emotions and in the Broca area of the brain that regulates speech.  Hmmm, social and speech areas being effect by a chemical released by a cell that is in a chain reaction caused by environmental causes that started in the gut with non-allergic allergic symptoms. Where we there yet?!?! Well not yet, yes there can be more…
 

Can you say Mitochondrial dysfunction 10 times fast

That alone sounded to me like it would be enough to cause Autism and had all fit so well with other research I had read about. As if that wasn’t enough, Dr. Theo started talking about the mitochondrial link with activated mast cells. Wait a mitochondrial linkage!?!  Oh yea, can you believe it.  It had to do with neurotensin again; it kept coming back to that damn molecule. At this point I thinkI was not writing, just staring at the Dr. Theo in disbelief.

Figure 6 - dyed images of mast cells showing placemetn of mitoconrdia in mast cells in the presense of neurotensin. The mitocondria, red, are seen clusteres around the cells nucleus in the middle row of images and are tight against the cell wall in the presense of neurotwnsin as seen in the bottom row of images.

It has been shown that the mitochondria in mast cells in the presence of neurotensin move to the surface of those cells and can move through the cellular boundary. This would not be a problem for most parts of a cell or almost anything else in the body, but mitochondria are an odd beast. Mitochondrial were bacteria that were made symbiotic with our cells millions of years ago so if they are outside a cell they are seen by the immune system as the bacteria they used to be millions of years ago. Once the mast cells start expelling their mitochondria it signals a bacterial infection and the immune system activates in an auto-immune response, yes auto-immune, yea yet another shoe, when does it stop!!!.
To further complicate it (is that possible) mitochondria are the power plants of our cells providing energy to the cell’s nucleus, they are found next to the nucleus. Once they move to the edge of the mast cell, they provide less energy to the nucleus and more to the production and release of the mast cell molecules increasing the activation process. In addition to all of the above, the resulting mitochondrial components once outside the cell have several effects in the body, including being a neurotoxin to brain nerves. So where are we, let’s add even more neurotoxic stuff in the brain and mitochondrial dysfunction and auto-immune, wow now we must be there. Now there better be proof that this is happening to autistic kids.

Oh wait he then showed how he tested for that. Dr. Theo showed some tests where mitochondrial DNA in the blood stream of autistic children is highly elevated, see figure 8. It comes out to like 10 TIMES the normal level on average.

Figure 7 – serum (blood) mitochondrial DNA (A) and anti-bodies (B) from typical and autistic children

This sure sounded like mitochondrial dysfunction to me and with auto-immune response to boot. I also then learned that these mitochondrial components can further this mast cell reaction by causing the release of more TNF- and Interluken-8(IL-8), see figure 8. IL-8 is yet another one of those molecules contained in mast cells and is used to cause inflammation. So now there was a link to brain inflammation and he had already showed links to neurotoxins, mitochondrial dysfunction, “brain fog” the breakdown of the gut-blood-brain barrier, allergies that are not allergies, and more. 

Figure 8 - test results showing an increased release of TNF and IL-8 in the presence of mitochondrial components

What about genetic links

That was about enough for me, I felt elated and beaten at the same time. So he decided to keep going. There was some recent research that a common “de novo” (out of nowhere) gene mutation in autistic kids is in an area where a protein called mTOR is created. This stuff called mTOR that is being messed with in the DNA of autistic kids is directly involved in mast cell activation and growth. Yea that would be a genetic link, need I say more on that subject.
Caution this may ruin your day – or just piss you off

If you want a hint at where these genetic mutations could be coming from look up www.soundchoice.org, they are a pharmaceutical institute (yea I said Pharma, but keep reading it gets reaaalllllll good) that is raising the flag on vaccine safety. They may have found that missing link to vaccines… No, drop the “may” part. And guess what, it has to do with aborted fetal stem cell The fetal Stem cells are what are used to grow the viruses for the vacine, in large vats. Then they filter out the contaminants, unfortunatle a lot of the DNA from the stem cells gets through the filters they use. Now if the cells were from any other animan this would not be a problem, our body would just discard the information. Unfortunately human stem cell DNA can get connected in with our DNA, low risk they say.

  
The "good" news is that it is only used to make a few vaccines; MMR, chickenpox, Hep A and B, a few others. If I remember correctly some of those vaccines seem familiar. Who would have thought the MMR would be unsafe, Oh yea Dr. Wakefield did like almost 2 decades ago. Well if you haven’t lit your hair on fire and run screaming across the room you may be wondering how could that be true. Where did this evidence come from?  ..… Wait for it …..  Merk and the Department of Health. I wonder if they can call bias and fraud on their own data?? If you really want to get even angrier see http://www.soundchoice.org/research.html .

A full list of contaminated vaccines and some non-contaminated versions is at http://cogforlife.org/vaccineListOrigFormat.pdf

I also wonder if a good avenue to correcting this is to get the pro-life movement involved. I am sure they do not want dead babies being injected into their kids.

Now for some good news

Ready for something a little more uplifting now? Let’s go to our happy place for a minute and talk about something on the constructive side. There is some great news on the detection and prevention fronts. Yes like medical test testection and a path twards prevention.

Dr Theo’s research has found some biomarkers (tryptase, IL-6, CRH, neurotensin) that can be tested for to see if someone is susceptible to or has Autism. This would have been great when my daughter was constantly sick for 8 months and in and out of the hospital. I know my doctor thought for a long time that my daughter might be autistic, but I had to wait more than 6 months before a real diagnosis was given. I can only imagine if I had started 8 months earlier (16 months vs 24) that does make a difference. Now there are biomarkers (things in the blood that can be tested) that could allow doctors to test on a child at any age and lead to earlier diagnosis and treatment.

The even better news Dr. Theo had was that there are supplements that will block 90% of the release of the harmful molecules from mast cells and possibly stop the mast cell activation completely. Tests proved that mast cells in the presence of certain Flavanoids (think vitamins, but different), particularly luteolin and quercetin, mast cells do not activate. If the mast cells stop degranulating/activating, this chain reaction with neurotensin could stop. This can allow the body to heal itself or possibly, if given early enough, prevent autism completely. An additional benefit of these flavanoids is that they are anti-inflammatory and block t-cells, which have been seen to have negative effects in autism.

So there must be a problem, well one small one. The problem with Flavanoids is that they are not absorbed by the body very easily. Dr Theo, is working on creating a drug to block neurotensin and other reactions associated with this response, but that takes time so while that work goes on he has worked with a company called Algonot (www.algonot.com) to create a supplement that will provide extremely pure flavanoind in a medium that will assist absorption.

So how can this all help

This product called NeuroProtek was released in 2010 and my wife and I started our daughter on it over a year ago and have had great results so far. Within a couple weeks her stool (always a topic of discussion) became regular and has been as long as she is on NeuroProtek (unless she is sick, then all bets are off). She started to show empathy and even speak. It was a month after we started her on it when we went to Christmas and My brother and Mother were amazed at the difference in a couple months. Sophia was empathic, friendly, giving hugs and kisses (she had NEVER done that before) and wanted to show off presents. When school stared the next January the teacher could not believe it and we had to completely redo the IEP. All the aggression at school subsided and speech started coming along. It was also as if her brain cleared up and she has been able to learn and start to catch up, just an amazing thing. I know I am not alone in this, since at the 2011 Autism One conference I talked to several DAN doctors that were using NeuroProtek with similar results. One Doctor said that 70% of the children on it had dramatic positive improvement and the rest also improved just not as dramatic. There is also a large clinical study of NeuroProtek going on in Greece (yes even with the financial issues they are having) and preliminary results have been excellent.
 

For more information on the supplement Dr Theo has worked to create with these flavanoids - NeuroProtek  http://www.algonot.com/neuroprotek.php .

If your child is Phenol sensitive they have a low phenol version for that too NeuroProtek-LP

So who’s getting rich here

Dr. Theo makes no money off NeuroPtotek, all proceeds go back into autism research. He has kept all this research going with almost no money. 50 grand from NAA and some from Autism speaks, Safe Minds, and other groups. He is working to get somereal govermetn funding, but if all this can be done for like 100k, imagine what is possible.

Last bomb I promise

Oh did I mention he is working on a medicinal food. That is a prescription, yes like doctor's prescription, like FDA approved "this really works" and your mainstream doctor will be all over it like a dog with a new toy. It will be nice to actually have a prescription for autism. (anyone’s head explode yet?)

 

A Word document of this article is attached below.
 

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Eben Plettner,
May 29, 2012, 9:33 AM
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Eben Plettner,
May 30, 2012, 8:06 AM
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