Showing posts with label Autsim drug therapy. Show all posts
Showing posts with label Autsim drug therapy. Show all posts

Thursday 12 June 2014

Cognitive Enhancement, Classic Autism and School

The school year is coming to an end and now we get the results of assessment week, the end of year tests.

Personally I never liked exams, or rather revising for them, but for teachers, assessment is a big part of what they do.  I used to be asked at the start of the school year for a list of benchmarks to measure my son Monty’s progress during the year, since the usual benchmarks were seen not as applicable.  Then we would spend lots of time discussing the list.

Typical kids just follow the standard curriculum and get their standardized progress tests.  If you follow an ABA program, you are constantly measuring performance and you only progress when you master a skill, so it is like continuous assessment.

Monty, aged 10 with ASD, goes to a very small international school.  So there is no special needs teacher, no IEP (individual educational plan), just a nice friendly environment.  This works very well because it means you can build your own educational system, not restricted by any rigid rules.

From the age of about four years old till seven or eight, in effect, Monty’s curriculum was the ABBLS (Assessment of Basic Language and Learning Skills), which is a rather intimidating list of 544 skills from 25 skill areas including language, social interaction, self-help, academic and motor skills that most typically developing children acquire prior to entering kindergarten.  These are very basic skills, that we never had to teach to Ted, Monty’s big brother, but without these skills you really cannot do much. They are the basic skills on which everything else is built.  It includes things like toilet training, stacking coloured blocks in order and, at the intellectual end, involves ultra-basic speech, being about to count and being able to read.

When your child has just a handful of these 544 skills, it appears that you have a mountain to climb; indeed you do.

Fortunately for us, Monty’s then Assistant and best pal, Irena, took on much of this daunting task.  He did become verbal, he did learn to read, he learned how to write and yes, finally, got to grips with numeracy.  (All without any help from drugs)  

This all occurred in parallel with going to "school".  The learning all occurred at home, school was just for practice.

Back then, the end of year report did not really have much importance.

At some point you do hope that school will actually be a place for learning.

It does appear that in many cases of “inclusion”, school is little more than daycare.  Some special schools are brilliant, but even if you live near one, they tend to be hugely expensive and access is highly restricted.

My observation of the limited number of people with autism I am familiar with, is that they tend not to get on with each other; they actually like to be around nice friendly neurotypical kids.  Until you get to secondary school, many kids are nice to special needs kids.  After that, most really are not nice at all, and any idea of going to school for “socialization” becomes nonsense, because the “normal” kids openly seem to ignore, provoke and even hate the kids with HFA/Asperger’s.  Sad, but true.

What is Normal for Kids with Classic Autism?

Most kids with classic autism end up in a special school, or a special needs unit attached to a mainstream school.

One of our former 1:1 assistants was a trainee at the local special school and later became a teacher at another one.  We discussed what went on there and I did visit a few the school a few times.  It was much better than I expected, but was more about keeping the kids calm and under control, than academic advancement.  There were 6 kids per member of staff and the kids had very mixed ability, they were just grouped by age.

I took a look at Treehouse, the leading autism school in London, to see what is in their curriculum.

In the US there are many such schools.  In Europe, Treehouse is quite well known, because it seems to be unique.  One of our former ABA consultants from the US used to work at Treehouse and another former one is on the Board of Governors.  Our current ABA consultant was doing her PhD in Behavioral Science in the US, when the founders of Treehouse visited the leading US autism schools for inspiration many years ago.  A small world indeed.

In fact the Treehouse curriculum bears little resemblance to what goes on in mainstream schools.

I really do not understand what kids with classic autism can achieve in big mainstream schools, even with an assistant.  I just discussed this with Monty’s teacher, how can you “include” a child who has no understanding of what you are teaching the other kids?

Two year ago I agreed with our school to hold Monty back by two years, to be at his academic level, so he is two years older than most of his classmates.  There is no rush to get to secondary/high school.

The question I have had for a long time is whether Monty will be able to learn at school.  To date he has had thousands of hours of 1:1 learning at home, following his home program, which now combines ABA-based learning of things like social skills, conversation etc., with academic work like numeracy and verbal comprehension.

School for Learning?

My plan, when I realized that drug interventions do really cognitively improve autism, was to retain my model of school in the morning and 1:1 learning at home in the afternoon and aim for a time when school could genuinely be for learning.

The good news is that we really do seem to have reached that point.

I had the end of year meeting with Monty’s class teacher and it was almost as if we were discussing a regular kid.  For a start, we were discussing results from standard tests for science, maths and English provided by Cambridge University for international schools following their primary curriculum, so much less scope for the usual “sympathy grading”.

Lots of kids do get extra time in tests, for example if they have dyslexia.  Why not for autism?    The Asperger’s boy in Monty’s brother’s class gets an easier English test and extra time.

In Monty’s case, I did not want extra time; anyway he does not need it.  If he does not understand what to do, extra time is no help.  The question was whether his assistant should give him any “hints” as to what the questions mean, when she knows he really does know the answer. (e.g. when asked verbally by the teacher, so not in writing,  "what is the next factor of 5, after 30")

We had this debate and we agreed; no help of any kind.  That way at least the test tells us something useful.  If the test is based on prompting/help, how big was the prompt?  Better to see the real result and then we can do the “oh, but he really can do that”.

So this year was the first time we have the same tests as the other kids and definitely no help.  This is the result:-

Speaking and Listening        C+
Reading                                 B+
Writing                                   B+
Mathematics                          C+
Science                                  A-
ICT                                         A+
Music                                      A
Art                                           A

Well the results show Monty ended Year 3 ahead of anyone’s expectations, including the teacher.

I think the art teacher was probably being over generous, which is what tends to happen (sympathy grading).  ICT (Information and Communication Technology) is pretty basic at this level, but Monty can do it all.  When it comes to music, Monty is in his element; he can read music, plays his piano and has started to sing.

So the grades seem to be genuine, and he was not at the bottom of the class in any subject. That might not be a common educational benchmark, but I think it is a pretty good one to see if “inclusion” is really working.

As I said to his present teacher, only two years ago he was hitting his then class teacher, assistant and even, on rare occasions, his classmates.  Back then there was very little learning going on at school and not much social interaction either.

Cognitive Enhancement

Along with greatly improved social skills, simple conversation with peers, and even some sporting ability, has come cognitive enhancement.  He still is not “normal”, but it is a remarkable transition nonetheless.

How far he can get following the mainstream curriculum is an open question, but it is far further than anyone could have dreamed of, until he started his drug therapy.

I continue to be amazed, but the gains are almost entirely reversed if he stops taking his drugs.

Tuesday 8 April 2014

PolyPill for Autism - Current Version

The objective was to identify the most effective drugs to treat Classic early-onset autism, having biomarkers of elevated serotonin, cholesterol, thyroid FT3/4 and growth factor IGF-1.  Except for the TRH drug, these drugs are all generic and very cheap.  The total cost per day is about EUR 1 ($1.4).

The dosage is based on a 10 year old child weighing 33kg / 73lbs

The TRH and Clonazepam doses are tiny.

According to the European Medicines Agency (EMA), most countries have an arrangement whereby patients can apply for access to drugs for off-label use, usually based on experimental evidence or clinical trials.  If you use these drugs, it would be helpful to collect data on the effect, so that it can later be used by the EMA to evaluate the Autism Polypill.  You can send me the data or case reports.

Since most doctors continue to regard autism as untreatable, you will have to be proactive, if you want a drug to treat your child. 

Thursday 19 September 2013

Polypill for Autism

A polypill is a pill that contains multiple pharmaceutical ingredients.  The idea is that for common conditions, like cardiovascular (heart) disease, a very cheap one-size-fits-all pill would actually bring great health benefits.  Many people in rich countries do not bother to take multiple pills and in poor countries most people cannot afford them, or cannot afford to visit the doctor more than once.

In the case of heart disease, it was shown that such a pill would cost about 10 cents and would be highly effective and extend people's live by several years.  Perhaps the Penny Pill might be another name for it.

Polypill for Autism

The main problem with autism is that 90+% of doctors are not even trying to treat it and are unaware of even the limited knowledge that does exist, to diagnose and treat sub-types (eg Landau-Kleffner syndrome).

So it would be clever to develop a one-size-fits-all pill and even if one or two of the ingredients were ineffective in a particular patient, overall there would be a big benefit.  I was then thinking what I would put in the Peter Polypill.

The Theoharides Polypill(s)

I was pleasantly surprised to find that somebody else has had the same idea and has gone so far as to patent it.  Dr Theoharides, from Tufts University in the US, has filed patents on several such polypills.  I have read much of his autism and mast cell research and was beginning to wonder why, after 25 years in the field, he has only brought to market an OTC supplement (Neuroprotek).

Just take a look at what he would put in his autism polypill:-

and more recently a very similar one:-

If you are a doctor or science graduate, you will probably read the full patent information, but if not, here is a summary:-


(Methods of treating autism spectrum disorders and compositions for same)

[0007] It has been discovered that measurement of certain serum markers capable of making brain blood vessels leaky can identify patients with ASDs. It has also been discovered that certain compositions can inhibit leakage of brain vessels that would otherwise allow entry of noxious molecules in the brain. The compositions disclosed herein have been found to improve the conditions associated with ASDs through inhibition of blood vessel leakage, as determined by behavioral improvement and as noted in the examples disclosed herein. Together, these data support that modulation, and, in particular, inhibition, of brain blood vessel leakage is a valuable intervention point for the treatment of ASDs. This discovery has been exploited to develop the present application, which includes methods and compositions for treating ASDs in a subject, as well as methods for screening for an ASD in a subject suspected of having an ASD.

[0008] One aspect of the application is directed to a method of treating an ASD in a subject. In this method, a composition comprising of one or more flavonoids, alone or in combination with, a serotonin blocker, a histamine- 1 receptor antagonist, a histamine-3 receptor agonist, an antipsychotic agent, a heavy metal chelator, a neurotensin blocker, olive kernel extract and a physiologically acceptable carrier, is administered to a subject in need thereof, wherein the composition modulates the leakage of brain blood vessels.



The invention comprises compositions for human use containing one or more of a flavonoid compound, a non-bovine heavily sulfated proteoglycan, an unrefined olive kernel extract, a sulfated hexosamine, S-adenosylmethionine (“SAM”), histamine-1 receptor antagonists, histamine-3 receptor agonists, antagonists of the actions of CRH, folic acid, a straight chain polyunsaturated fatty acid, a phospholipid, a polyamine, an interferon and glutiramer acetate, together with appropriate excipients and carriers, said compositions having improved absorption from the gastrointestinal tract, skin surface, and nasal and pulmonary surfaces, and anti-inflammatory effects synergistic with each other and synergistic with available conventional clinical treatment modalities.

It has been discovered that various combinations of a sulfated proteoglycan, unrefined olive kernel extract, a flavone (a.k.a. flavonoid compound), a sulfated D-hexoseamine, a phospholipid, a long chain unsaturated fatty acid, a CRH antagonist, a histamine-1 receptor antagonist, a histamine-3 receptor agonist, glutiramer acetate, an interferon, and a polyamine have synergistic anti-inflammatory effects when used as a dietary supplement, a topical product or an aerosol for nasal or pulmonary administration, without or with a conventional clinical treatment for inflammatory diseases. Within the present context, such inflammatory diseases result from the activation, degranulation and consequent secretion of inflammatory biochemicals from mast cells, and the resultant inflammatory diseases include the group consisting of: allergic inflammation, arthritis (to include osteoarthritis and rheumatoid arthritis), fibromyalgia, chronic fatigue syndrome, inflammatory bowel disease, interstitial cystitis, irritable bowel syndrome, migraines, atherosclerosis, coronary inflammation, ischemia, chronic prostatitis, eczema, multiple sclerosis, psoriasis, sun burn, periodontal disease of the gums, superficial vasodilator flush syndromes, hormonally-dependent cancers, and endometriosis. The olive kernel extract alone may be used to improve the transmembrane transport of difficultly-absorbable biomolecules in the intestine, skin and pulmonary alveoli.

The patent goes into great detail of exactly which drugs might be included, and in the second patent even the dosages.

Histamine H1 and H3 Agonists

I wrote extensively in this blog about histamine and autism.  Theoharides proposes to use an H1 agonist and an H3 agonist.  The problem is that H3 agonists are still experimental and unlicensed; however his choice of possible H1 agonists is very interesting and something that can be applied today.

Azatadine is an antihistamine and serotonin blocker

Azelastine is a second generation antihistamine and mast cell stabilizer available as nose spray or eye drops.  Seems to be the most effective for hay fever.  OTC in UK

Cyproheptadine or Periactin is a first generation antihistamine with additional anticholinergic, antiserotonergic, and local anesthetic properties.    OTC in UK

A clinical trial exists in autism of this drug.

Hydroxyzine another first generation antihistamine. Due to its antagonistic effects on several receptor systems in the brain, hydroxyzine is claimed to have strong anti-anxiety and mild antiobsessive as well as antipsychotic properties

Merelastine is another first generation antihistamine

Rupatadine is a second generation antihistamine and PAF antagonist used to treat allergies.  It has mast cell stabilizing properties.

Antipsychotic and Chelator

I was surprised to see these drugs mentioned, the heavy metal chelator is meso-2,3-dimercaptosuccinic acid (DMSA) and  the antipsychotic agent is risperidone.

The evidence for chelation actually looks a bit shaky.  In fact two antioxidants proposed for use in autism, NAC (N-acetyl cysteine)  and ALA (lipoic acid) are highly likely to remove any heavy metal nasties anyway.

Mitigating Methyl mercury Exposure: Study Confirms Potential of NAC as Antidote and Biomarker

I will be sticking with NAC and certainly not using antipsychotics, since they are known to have major side effects.

Neurotensin blocker

Neurotensin (NT) is another neurotransmitter.  Neurotensin has been implicated in the modulation of dopamine signaling, and produces a spectrum of pharmacological effects resembling those of antipsychotic drugs, leading to the suggestion that neurotensin may be an endogenous neuroleptic.

Children with autism have elevated levels of NT and the level seems to correlate with the severity of their autism.

Neurotensin blockers have existed in research for some time, but there is no licensed drug.

Serotonin blocker

The serotonin blocker is azatadine or cyproheptadine.  Both of these are actually H1 histamine antagonists.  Cyproheptadine, also known as Periactin is available OTC in some countries, including the UK.

SAMe, folic acid

Supplementation of the compositions described above with the methylation reagent S-adenosylmethionine (“SAM”) adds antioxidant, anti-inflammatory and cytoprotective properties, particularly in inflammatory joint and cardiovascular diseases. Addition of SAM also accelerates metabolism of homocysteine, which amino acid has been implicated in coronary disease, to cysteine, which is harmless. Folic acid may be added to certain of the present formulations for similar reasons.

In fact NAC + B12 is an alternative way to reduce homocysteine levels, as already mentioned in an earlier post.

The Peter Polypill

I found Dr Theoharides patents very interesting and it is encouraging to see that someone is actually doing to some research, reading other peoples research and trying to bring products to the market.  

Of Theoharides’ ingredients, the ones I would also include in the Peter Polypill are the H1 agonists (including the serotonin blocker).

The Neurotensin blocker and H3 agonist look interesting, but it will be many years before they are licensed as drugs.
The hypothetical Peter Polypill is currently as follows:-

A twice daily effervescent tablet containing:-

Atorvastatin, with co-enzyme Q10 added to counter the secondary effect of the statin

Bumetanide, with Ca, K, and Mg added to counter the losses due to diuresis

NAC plus a small amount of acetyl-L carnitine

Rupatadine, as H1 agonist and mast cell stabilizer

Taltirelin hydrate, the TRH analog

Vitamins D, B6, B9 and B12 + selenium

Then I would give Dr Theoharides oil-based flavonoid supplement to help stabilize mast cells and maybe, before bed I would add Periactin, the sedating H1 anti histamine and serotonin blocker.  For summertime allergies, it looks like the nasal spray containing Azelastine should be the best.