This brief post addresses one further
issue as to why people with autism can often suffer from various nasty gastrointestinal
(GI) problems.
First a recap.
Mast Cell
Activation
We have already seen that some people’s GI
problems are caused by mast cell activation/degranulation. These cells are activated by allergens
(certain foods in this case) and then they release histamine and other
pro-inflammatory agents like IL-6.
Degranulation of mast cells can itself cause pain, but the main problem
is the resulting damage/inflammation caused by the IL-6 and histamine.
The effective therapy is a mast cell
stabilizer. These include Verapamil
(better known as a calcium channel blocker), Cromolyn Sodium, Ketotifen,
Azelastine and to a lesser extent most anti-histamines like Claritin, Zyrtec etc. Quercetin, the flavonoid, also has an effect.
Pancreatic
Dysfunction
We also saw that L-type calcium channel (Cav1.2)
dysfunction in the pancreas may disrupt the production of certain digestive
enzymes. The lack of these enzymes will
disrupt the digestive process and likely affects other processes elsewhere in
the body. Verapamil blocks the Cav1.2
channel.
Ulcerative
Colitis
We saw that inflammation and colitis, as
diagnosed by an endoscopy, is another comorbidity of autism; this may be in
part caused by the mast cell degranulation, but it does fit with the broader hypothesis
of the over-activated immune system. We
saw how the potassium ion channel Kv1.3 was the mechanism behind some useful
immuno-suppressive therapies, including those TSO parasites. For those who are skeptical, here is another
recent study, I just found:-
Kv1.3 should then be a target to treat
ulcerative colitis and, I believe, autism itself. Some Kv1.3 blockers exist
today; one is Verapamil, another is Curcumin, for those who prefer
supplements to drugs.
Before I forget to write this down
somewhere, it appears that Kv1.3 can also be modulated by PKA and PKC, which
decrease its activity.
We have already come across protein kinase B (PKB) and there will be a post soon of
PKA, PKB and PKC. This all links back to
oxidative stress, neuroinflammation and even those dendritic spines.
Reflux
Today’s post is about reflux, sometimes
known as gastroesophageal reflux disease (GERD) or gastro-oesophageal
reflux disease (GORD). Reflux is when the acid from the stomach rises
through the esophagus/oesophagus to the mouth.
Many adults suffer from reflux from time to
time and there are many OTC and prescription drug treatments. It can cause pain
and discomfort, and would be particularly troubling if you could neither
verbalize, nor understand your symptoms.
Why this
post?
You may wonder why I have jumped from
broccoli (the previous post) to reflux.
There is a reason.
I was recently listening to a conversation
between doctors about a head-banging child and then came “it’s not autism; he’s
got reflux, that is why he was banging his head.”
That sounded very odd to me.
It turns out many people with autism suffer
from reflux, so you could say it is a comorbidity. But why might that be?
mGlu5 receptors and disease
In an earlier, rather complicated, post I
introduced the glutamate receptor, mGlu5.
This receptor is at the centre of research into Fragile X at MIT. Fragile X is the most common single gene
cause of autism. It has been shown that
mGlu5 dysfunction appears in many types of autism and indeed schizophrenia
(adult-onset autism).
I then chanced upon a recent paper on mGLu5
and came across this section:-
Through contributions to synaptic plasticity, mGlu5 receptors have been implicated in neuronal
processes such as learning and memory as well as disorders including Fragile X
Syndrome (FXS), tuberous sclerosis, autism, epilepsy, schizophrenia, anxiety,
neuropathic pain, addiction, Alzheimer’s disease, Parkinson’s disease,
L-DOPA-induced dyskinesias, and gastroesophageal
reflux disease
That was quite a surprise, but yet another
good lesson of why the comorbidities should all be carefully researched.
The full paper, for anyone with time on their
hands is:-
Conclusion
If you have
autism, you may have an mGlu5 dysfunction.
This will become treatable once the needed PAMs (Positive Allosteric
Modulators) and NAMs (Negative Allosteric Modulators) have been brought to
market. A great deal of research is
ongoing.
In the
meantime, mGlu5 dysfunction is quite possible elsewhere in the body. mGlu5 dysfunction is associated with some
very rare disorders, but the common ones are diabetes and reflux.
The
head-banging boy very possibly had both autism and reflux; he did develop
diabetes.
For more on
autism and diabetes, a short, thought provoking, but technical, paper:-
Interestingly,
we saw earlier that Verapamil seems to offer protection against type 1 and 2 diabetes.
This time it is its calcium channel blocking role that is the mechanism.
No big surprise that Verapamil is an ingredient of the autism Polypill.