Today’s post revisits the idea of
using immunotherapies to treat autism.
Some readers of this blog are already
doing this and a significant percentage of those are using IVIG.
Intravenous
immunoglobulin (IVIG) is a pooled antibody, and a biological agent used to
manage various immunodeficiency states and a plethora of other conditions,
including autoimmune, infectious, and inflammatory states.
IVIG is not a precision therapy, it is
more a case of when all else fails try IVIG.
In the United States it seems that
many insurance companies will cover the cost of long-term IVIG therapy. In
other countries the cost greatly limits the use of this therapy.
An interesting observation is that
IVIG products can vary significantly in their potency, depending on where they
are made. Several readers of this blog have noted this.
I attended the Autism Challenges and
Solutions conference recently in Abu Dhabi. I did have a chat with Laila
Alayadhi, a researcher and clinician from Saudi Arabia who has been publishing
papers about autoimmunity in ASD for decades. She also published a series of
studies that examined the potential of camel milk as a therapy. She examined
both changes in biological markers of oxidative stress and inflammation as well
as measures of autism severity.
Her most recent study is here:-
The link between nutrition and autism spectrum disorder (ASD), as a neurodevelopmental disorder exhibiting impaired social interaction, repetitive behavior, and poor communication skills, has provided a hot point of research that might help use nutritional intervention strategies for managing ASD symptoms. This study examined the possible therapeutic potency of raw and boiled camel milk in reducing neuroinflammation in relation to behavioral characteristics. A blinded study was conducted on 64 children with autism (aged 2–12 years). Group I (n = 23) consisted of children who received raw camel milk; Group II (n = 27) comprised children who received boiled camel milk; and Group III (n = 14) comprised children who received cow milk as a placebo. Changes in plasma tumor necrosis factor-alpha (TNF-α) as pro-inflammatory cytokine in relation to behavioral characteristics evaluated using the Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and gastrointestinal (GI) symptoms before and after 2 weeks of raw and boiled camel milk therapy. Significantly lower plasma levels of TNF-α were recorded after 2 weeks of camel milk consumption, accompanied by insignificant changes in CARS and significant improvements in SRS and GI symptoms. Alternatively, Group III demonstrated an insignificant TNF-α increase without changes in CARS, SRS, and GI symptoms. This study demonstrated the positive effects of both raw and boiled camel milk in reducing neuroinflammation in patients with ASD. The improvements in the SRS scores and GI symptoms are encouraging. Further trials exploring the potential benefits of camel milk consumption in patients with ASD are highly recommended.
Apparently camel milk tastes just fine, although Dr Alayadhi told us she had never tried it prior to her research. She has shown than both pasteurized and raw milk are equally effective. I did ask her about other types of milk like goat’s milk and she said they had tried other milks and that only camel milk has shown the immunomodulatory effect. When asked how much you need to drink, the answer was three glasses a day.
The Dentist
I did chat to another Saudi professor, a pediatric dentist, who gave a presentation about treating children with ASD. Having had some pretty bad experiences with getting dental treatment and then overcoming them, I did feel I had something in common with Ebtissam Murshid. I did catch up with her later and shared details of the D-Termined program created by US dentist David Tesini. It is a video training program for dentists how to treat kids with autism. I have written about it previously in this blog. Tesini very much tries to make the visit to the dentist fun, with lots of distractions in his treatment room. Murshid purposefully has blank white walls, believing that autistic kids get upset by bright colors and patterns. Hopefully she watches Tesini’s videos.
Murshid has published a book to help
parents prepare their children for their trip to the dentist and, like Tesini,
had made a small trial to show that her method is effective.
Some dentists are naturally good at
treating the most difficult kids, but most are not. It is impossible to predict.
A really good dentist needs neither
restraint, like a papoose board, or sedation. If general anesthetic is needed,
then something is not being done right. Kids with severe autism can be treated
with local anesthetic just like other kids, they just need to go through a
familiarization training like Tesini/Murshid use.
Back to
immunotherapy
I did have many conversations with
Carmello Rizzo who is an Italian doctor interested in both diet and
autoimmunity to treat autism. He is a feature at many autism conferences and is
a great speaker. He was telling me about Enzyme Potentiated Desensitization
(EPD), an overlooked way to treat allergy care.
EPD was invented in the 1960s by a
British immunologist Dr Len McEwen, at St. Mary’s Hospital, Paddington. EPD is
approved in the United Kingdom for the treatment of hay fever, food allergy and
intolerance and environmental allergies.
It is an unlicensed product (i.e. not
a drug), it is available only on a “named patient” basis.
EPD is not the same as allergy shots.
Allergy shots, also known as allergy
immunotherapy, are injections used to treat allergies over a long period of
time. They work by gradually desensitizing your body to the allergens that
trigger your allergy symptoms.
Allergy shots typically involve two
phases, buildup and maintenance.
It is an escalating dose immunotherapy,
when you gradually increase the exposure level of the identified allergen.
The buildup phase lasts for 3 to 6
months. You receive shots 1 to 3 times a week. The doctor will gradually
increase the amount of allergen in each shot to help your body build tolerance.
In the maintenance phase you need
shots less frequently, usually about once a month. This phase can continue for
3 to 5 years or even longer depending on your progress.
I was never interested in allergy
shots because there are so many injections needed.
I found EPD of interest because you
take just two shots a year and the effect may potentially control the allergy
after 2 or 3 years.
EPD is not expensive and I suppose
that is why nobody wanted to invested the tens of millions of dollars to get
approval by the FDA. It remains approved for use in the UK, which is ultra
conservative when it comes to medicines.
Carmello Rizzo is offering EPD in
Italy and elsewhere.
Gene therapy for
autism?
I did go to a presentation with an
interesting title:
Developing
effective therapeutics for Autism Spectrum Disorder
It was not really what I was
expecting. It was a young MIT researcher talking about the potential to develop
gene therapies to replace mutated genes with a new ones. They are doing this in
a model of autism caused by a mutated copy of the SHANK3 gene.
I called him Dr Viral Vector and did
have a chat with him. The most interesting thing about his technology is that
not only can he target a specific type of cell, but he can target a specific
part of the brain, or indeed any part of the body.
At the moment they inject a virus
carrying the new gene directly into the brain. That is not going to go down so
well with human subjects. The next stage is to try injecting the virus into a
vein.
I did talk about the two gene therapies
for Rett syndrome now in human trials in my presentation. The ultimate problem
is the likely $3 million cost.
You can use gene therapy as an immunotherapy.
Artemis
At
the conference I was asked about a gene called DCLRE1C, it encodes the DCLRE1C protein, also known as
Artemis.
Artémis (Diane), the huntress. Roman copy of a Greek statue, 2nd century. Galleria dei Candelabri
Source:
By Jean-Pol GRANDMONT - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=18604889
The
Artemis protein is named after the Greek goddess Artemis, who was associated
with the hunt, wilderness, wild animals, childbirth, and protection. This
connection likely comes from the crucial role Artemis plays in DNA repair,
which is essential for maintaining the integrity of the genetic material, like
a protector safeguarding the building blocks of life.
Complete
loss of function in DCLRE1C typically causes severe combined immunodeficiency. This is called Artemis-deficient
severe combined immunodeficiency (ART-SCID).
Fortunately many possible mutations only
partially impair the function of the DCLRE1C gene. They can lead to a spectrum
of conditions, including atypical SCID, Omenn syndrome, Hyper IgM syndrome, and
even just antibody deficiency. These conditions may have milder symptoms
compared to classic SCID.
IVIG is a beneficial therapy for immunodeficiency; but is very expensive and not curative.
Humans all have 2 copies of the DCLRE1C
and it is theoretically possible to increase expression of the good copy. But
that is another story.
A
gene therapy already exists for full-on ART-SCID.
Lentiviral
Gene Therapy for Artemis-Deficient SCID
Why not use it in less severe cases?
The problem is going to be money, both
for a lifetime on IVIG or a “hopefully” one-off gene therapy.
One lady in the audience of my talk had
herself taken an expensive gene therapy and was not impressed.
Other interesting
presentations
Pierre Drapeau from McGill University
spoke about trying to repurpose a cheap old drug, called Pimozide, to treat
motor neuron disease /ALS. This was
interesting because the process is similar to repurposing a drug for autism.
Pimozide is an old antipsychotic drug
and it seems to work in ALS through its effect on a type of calcium channel
called the T-type. Yes, just as in much autism, calcium channels are
misbehaving.
The drawback of Pimozide is that it also
blocks dopamine receptors in the brain, which is good if you have Tourette’s,
but if you have ALS you then get symptoms of Parkinson’s as a side effect.
The solution is to tinker with the
molecule and find a version (an analog) that will do the business with the T
channels without causing tremors. It
looks like, via trial and error, this is nearly solved.
The whole process has already been going
on for many years, it will take many more.
Life expectancy with ALS is only 2-5
years and they struggle to find test subjects in Canada. It looks like they may
do trials in China.
An eye opener
A presentation with a very hard to
digest title was also an eye opener. You can take a picture of the cornea in
your eye and accurately diagnose all kinds of disorders. They started with
peripheral neuropathy in diabetics and most recently moved on to people with
autism. Using artificial intelligence (AI) they can now make a diagnosis just
based on the nerve loss they observe in the cornea. They also can potentially measure
the effect of therapies by the regeneration of those nerve fibers. This is really clever. When Rayaz Malik
started down this path, all the neurologists thought he was mad. Many years
later and corneal confocal microscopy is widely used around the world, but not
yet for autism diagnosis.
Antonio Persico is a well known autism
clinician, he appeared virtually. He was mainly talking about antipsychotics. I
had expected rather more.
Conclusion
Immunotherapy addresses one of the four problem areas in autism. There cannot be a one size fits all approach, but you can certainly try camel milk. Addressing food allergy and intolerance is relatively straightforward and you do not need any fancy expensive genetic testing, as Carmello Rizzo pointed out.
There are people for whom genetic
testing and/or a spinal tap opens the door to a precise diagnosis and hopefully
treatment. That proved to be an unexpected controversial issue in my
presentation.
My talk at the conference was all about
using personalized medicine to treat autism. The organizer of the event reads
this blog and knows that I am rather an outsider, since I am more in treating
autism than just researching it.
I had a two and a half hour time slot and I made sure to use it all.
Advances in Personalized Medicine to Treat Autism
I should mention that I also had some long conversations with Paul Shattock, who pretty much founded the gluten and casein free diet years ago, back at the University of Sunderland. If you are interested in the history of autism, he is a great person to talk to. He is nearly 80 years old, but still has a sharp sense of humour. He has stumbled into more than his fair share of controversies. In Abu Dhabi his opinions and observations were widely shared by other speakers. One younger American speaker thought his views were dangerous; had he taken the time to talk to Paul, he would have found them pretty well thought out. I did ask Paul what has happened to his old friend Andew Wakefield – apparently making another film.