PolyPill Reformulated

One reader of this blog, who found that 2.5ml of the Australian broccoli sprout powder, I suggested in an earlier post, works wonders for her son (40 minutes after the first dose), asked if I was going to include it in my Polypill.

Then yesterday Monty’s assistant at school asked to take some powder to try on another small child with ASD.  Today she tells me that the same positive result was repeated, in half an hour.

So I decided it is time to update the PolyPill.

I did tell the researcher, I was in touch with at John’s Hopkins, that it appears you can reliably make Sulforaphane at home, without your own laboratory and a deep freezer.  I think they somehow prefer things to be complicated and hard to access.

It does amaze me how people are not adopting, even super-safe, ideas that might help their child.  Many tens of thousands of parents affected by ASD must have read the stories in their newspapers about Broccoli (Sulforaphane) and autism.  How come almost nobody has made it work at home? Or at least, that is what it seems like if you look on Google.  People write about having read about it.  They usually then say, “ah well, Johns Hopkins say it does not work at home and you need a standardized dose”.

Sometimes you need to think for yourself.

Behind all this is the belief that “doctor” always knows best.  Most people are terrified of “experimenting” on their child.  Those that actually do this, are nearly exclusively in the US, with their DAN doctors.  They seem to give up after a year or two and accept whatever is left of the autism.

By the time the child is older and the parents are less worried about them trying drugs, they have given up and accepted the “inevitable”.

Reader feedback

When I started this blog, I rather optimistically expected to join forces with many other motivated, scientifically knowledgeable, parents.

This blog is visited 10,000 times a month, but I can count on two hands the number of people that have acted on it and shared their experience on/off line.  There have been some really great outcomes, which is wonderful for those concerned. (great outcomes = big improvements)

Without wanting to be biblical, but having recently sat through the film, Pulp Fiction, with Monty’s older brother, this does sum things up nicely:-

"Ask and it will be given to you; seek and you will find; knock and the door will be opened to you”

It just might take you a lot more work than you expected.

PolyPill

Regular readers will have noticed that the Polypill is my formulation for treating classic early-onset autism.  It is a combination of the clever ideas of others, some developed a little further, and some ideas of my own, based on the literature.

Many drugs and supplements have some impact on autism.  Some make it better, some make it worse, but most have no effect whatsoever.

Drugs and supplements can have side effects and they can react with each other.  So it is wise to use only those with a major impact.

Broccoli Sprout Powder

The most surprising ingredient I have tested is freeze dried broccoli powder from Australia.  Who would have thought that 2.5ml of this green powder would have an effect on autism.  But it does, and without any of the extra myrosinase, that I had expected to need. Johns Hopkin’s version is a deep frozen product, made after reacting broccoli sprouts with daikon radish sprouts in the laboratory.

All of people working with Monty, aged 11 with ASD, have noticed the difference, so it really is not a placebo effect

Incremental changes

·        Much more unprompted speech (> 50% increase)

·    He started to talk to animals and continues to do

·     He opened the car window to say hello and good bye to someone he recognized passing by – totally unheard of behavior

·        Increased awareness and presence of his surroundings

·        Now, while the TV news is on, Monty is reading aloud the news ticker at the bottom of the screen.  Before, the TV news was just “wallpaper”, unless there were some explosions  or other excitement.

·        Improved mood and mild euphoria

·        The broccoli powder still produces euphoria

·        In other people it may just improve mood

The good news is that Broccoli really is more of a food than a drug and so should not be harmful; although all kinds of things can interact in strange ways.  For example, vitamin C with cinnamon is not a good idea.

Method of action

As usual, I do like to know how and why things work.

The broccoli sprouts contain many substances, at least two of which might be involved:-

1.     Indole-3-carbinol (I3C).  I3C has some extremely interesting properties for both cancer and autism.  I3C up-regulates a protein called PTEN, encoded by the PTEN gene.  PTEN is an “autism gene”.

2.     Sulforaphane (SFN) is the chemical that John’s Hopkins think is the “active” ingredient of broccoli.

SFN is an activator of Nrf2, a “redox switch”.  This release of Nrf2 has a known on/off effect on about 300 genes involved in the response to oxidative stress.

SFN is also an HDI, or an inhibitor of HDAC (Histone Deacetylase)

HDIs have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics.

Interestingly, we learn from Wikipedia:- 

“To carry out gene expression, a cell must control the coiling and uncoiling of DNA around histones. This is accomplished with the assistance of histone acetyl transferases (HAT), which acetylate the lysine residues in core histones leading to a less compact and more transcriptionally active chromatin, and, on the converse, the actions of histone deacetylases (HDAC), which remove the acetyl groups from the lysine residues leading to the formation of a condensed and transcriptionally silenced chromatin. Reversible modification of the terminal tails of core histones constitutes the major epigenetic mechanism for remodeling higher-order chromatin structure and controlling gene expression. HDAC inhibitors (HDI) block this action and can result in hyperacetylation of histones, thereby affecting gene expression.”

So it looks like those little broccoli sprouts might be initiating some very clever science, perhaps even some primitive gene therapy.

Conclusion

There are still plenty more ideas waiting to test, so there will no doubt be more updated versions of the PolyPill in future.

It does look like there may be more food ingredients and not just drugs, which is not what I expected.

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.

Spiderman, and the Amazing Ted and Monty

Age-appropriate behaviour is not something you can really teach a child with autism.  In the toddler years, so many other children are behaving "badly", that nobody is really bothered by other toddlers with their autistic behaviours.  As children get older, the limits of acceptable behaviour change and it is then that many kids with special needs gradually get left behind. 

Monty, aged 10 with ASD, has a classmate from Angola called José.  Monty’s big brother, Ted aged 13, goes to the same high school as José’s big brother Eduardo.

Yesterday was José’s birthday party and so I decided to ask Ted if he would go to the party and look out for his brother.  Prior to this Monty always has had a parent close by, in full view, in case of need.

It turned out that the plan was to go to see a movie, Spiderman 2.  Ted had already seen it and said that it is really long; nearly two and half hours, and he thought that no way was his brother going to sit through that.  Also, it is not a baby cartoon film, it is PG13.

So we turned up at the mall as agreed at 5.30 pm, but it turned out that the film started at 7pm and before that the kids were to roam around a toy store before food at McDonalds.  That meant that they would finish at 9.30pm.  How was Monty going to survive 4 hours of big boy’s birthday party, with no Dad?

Ted is a typical teenage boy and so hanging out, in public, with an autistic brother is not something he wants to do.  In fact, he complains if I ever bring Monty to collect him from school.  I keep telling him that there is no need to feel embarrassed; the other kids just say “hey look, there’s Ted’s brother” and then some of the girls usually come and hug him.  There are no silly comments.

So for the first time ever, Ted would be alone with Monty, and for FOUR hours.

Ted did have a mobile phone and I was always in the building, getter further away, as the time past.

The result

Monty roamed the toy store with the gang of kids, had his Happy Meal at McDonalds, then the all-important birthday cake.  Ted made sure Monty visited the toilet and then all 15 of them went to the multiplex.  Ted bought his brother popcorn and they went inside.  At 9.30pm they all emerged with smiling faces.  Monty was happy, Ted was happy and nobody was embarrassed.

This is quite a step up from seeing the matinee performance of Rio 2 with Dad the weekend before; I think you could call it age-appropriate behaviour.

Without the Polypill, this would not have been possible, and we would have been home by 7pm, or even worse, we would have said “far too late to have a party, on a school day”.    

So it was a case of the Amazing Ted and Monty, rather than the Amazing Spiderman.

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. 

The Matryoshka in Autism - Revealing the Child Within

  

 

Matryoshka dolls are Russian stacking dolls, often mistakenly called Babushka dolls

Picture Source: Wikipedia

This post coincides with the first week of Putin’s Winter Olympics in Sochi.  All is going well so far and Russia has shown it can put on quite a spectacle.  Russia has no shortage of clever scientists, but rarely does their research make it into English language journals.  No doubt, much gets lost to the non-Russian speaking world.

Russia is famous for its Matryoshka dolls.  Remove the outer layer and see what is underneath.

Treating your child’s autism can also be like un-stacking your Matryoshka doll  for the first time.  You may be surprised what lies underneath. 
 

моя матрешка (My Matryoshka)

This week for me was another surprising one.

Monty, aged 10 with ASD, has an Assistant with him in the mornings at school.  “Has Monty ever been to Disneyland?” she asked me.  It turns out one of his classmates had been telling his friends about a family holiday to Disneyland Paris.  Six years ago we took Monty to Disneyland Paris.  All I remember was pushing him around the theme park in a pushchair, while his elder brother enjoyed the rides.  In the very many gift shops, Monty enjoyed reorganizing the stock into nice neat rows; but that was about it.  After that experience, we limited ourselves to Legoland; the best one is the original in Billund, Denmark, which is great for all kids.  I doubt Disneyland was a memorable experience.

So it was a great surprise to hear that Monty had joined the conversation at school and said that he too had been to Disneyland. Until very recently, he had never been able to join in any, unprompted, natural conversation.  Perhaps this was just his imagination, but when I asked him later who he had been to Disneyland with, he gave the right answer and I had structured the question to make the easy response the wrong answer. 

We also now have a lot of speech and much is directed at humour.  Monty is taking an observation and reinventing it, to make it more memorable and amusing.  So, Martin breaking his tooth at school playing football, when he collided into another boy, with the teacher Mr Keith looking on, transitioned through:-

Martin hit his teeth   (what happened?)

Martin was playing football with Mr Keith  (really, and then what?)

Martin was playing football with Mr Keith and broke his teeth

And finally

“Mr Keith broke Martin’s teeth”, which was repeated many times.

By which time he was in fits of laughter.  As long as we don’t tell Martin’s mother, all will be OK.

Yesterday, Monty informed me of the news about his 8 year old classmate:  

“Alexia has got married”   (Martin has been busy) 

Is this NT behaviour? No, possibly not, but it is unlike any autistic behaviour I have seen to date.

Today, a little girl at school stopped me and said “Monty talks funny; and I don’t know why”. 

Finally, the Head Teacher came up to me and says she keeps meaning to write us a note, to tell us how great Monty is doing this year, so happy and joyful.  Now he greets everyone spontaneously and no longer with any prompting.

So it looks like the outer shell of the Matryoshka has been consigned to history.    Long live the Polypill, and not to forget 12,000 hours of 1:1 therapy.

What lies deeper inside remains to be seen.



 

 

Who Pays the Piper? Off-Label or Polypill

It seems that autism is not the only “untreatable disease”, that does appear to be treatable.  At least twenty years ago, one apparently related condition was extensively treated off-label.  I am reading an intriguing book about the off-label treatment of Fibromyalgia in the 80s and 90s.

 

Off-label

In medical-speak “off-label” is when a drug is use for a purpose it was never actually approved for.  If you have straight forward diseases, you would never need to use a drug “off label”.

In some countries off-label prescribing by doctors is totally discouraged, in others, it is quite common.

The problem occurs when it comes to paying for expensive drugs and, of course, who is to blame if things go wrong.

Since many drug discoveries are actually stumbled upon by chance, off-label drug use is not as crazy as it may sound.

Socialized Healthcare, Private Insurance and Lawsuits

In the developed world, healthcare is provided either via some kind of private insurance as in the US, or it is via the State, as in Europe.  If your insurer is unwilling to pay for off-label treatments, you will not get them (unless you pay yourself).  In the UK, if the treatment is not endorsed by NICE (in effect, the State), you are not going to get it.  In the old days, the doctor might have been willing to try some off-label drugs, but now they are likely to be more worried about being struck of the medical register for malpractice, or, in the US, being sued.

So, all over the world off-label prescribing is getting rarer.  Certain states in the US are more liberal, Florida I believe is one.

Your healthcare is really in the hands of big brother; in general, this is not a bad thing.  If you have some rare, “untreatable” condition, then the problems start.  Even if you know what off-label drug you want, you will struggle to get it.  You will even struggle to get any unusual blood tests done.

In some countries the system is much more liberal.  If you want to measure potassium in your blood or maybe IGF-1 or serotonin, the process is akin to having your dry cleaning done.  You pay and it gets done.

 

Off-Label in the US

Before insurers tightening things up in the 1980s, doctors in the US seemingly were able to prescribe pretty much what they wanted.  If you read about some of the things prescribed for severer cases of Fibromyalgia, you would be amazed at the things they used (IVIG, Baclofen, Oxytocin etc.) and how the underlying principle was one of trial and error.

Due to the unusual position of osteopathic medicine in the US, where osteopaths have the same drug prescribing rights as medical doctors, there are many “alternative” doctors practising what they call “holistic medicine”.  Then there is a small army of DAN doctors, some of whom are medical doctors and some are not.  You also have a large number of chiropractors in the US; graduates of chiropractic schools receive the degree Doctor of Chiropractic (DC), as I was told by a reader of this blog, US  Chiropractors do not prescribe drugs, but they do treat kids with autism (I am not sure how).

So it looks like, while the golden days are over, off-label drug prescribing is alive and well in the US.

 

From Off-Label to On-Label

You would think that once an off-label therapy gets established, it would be able to transition to on-label, and become an accepted mainstream therapy.  This does not happen very often.  The doctors using off-label widely, are seen as quacks by some established doctors and by much of the public.  If they are treating unusual, hard to define conditions, it is hard to carry out controlled clinical trials, and nobody has an interest to pay for them anyway.

So, off-label tends to stay off-label and for most people, untreatable conditions remain untreatable.

Polypill

I am wary of my ideas being seen as risky, off-label, quack nonsense.  They certainly are off-label uses.

I think you should be able to transition from off-label to on-label.  If the disease is just a cluster of symptoms and pathologies, it will be hard to identify the sub-type for which the therapy is effective.  This applies to both autism and indeed fibromyalgia.

To move away from the very unscientific, and indeed wasteful, trial and error approach, you have to be able to use reliable biomarkers or diagnostic tests.  You would have to prove to a very cynical public, that you are not spouting nonsense.

Then faced with a therapy which can be shown effective consistently, albeit for a rare, very well defined, condition (based on blood tests etc.), there is no good reason why the therapy should not go on-label.

The question now with the Polypill is to be able to identify with >75% certainly for whom it will be effective.  I also need to understand, and indeed predict, when it might stop working.  This may sound very strange, but can happen.

Predicting when it might stop working, as well as suggesting what to do should that occur, makes things tricky. To do it perfectly you would really need the old school off-label doctor, and a vast amount of consultation time, that will not be available.

I live in a country where access to lab tests is very open and they are inexpensive, so I have come up with a testing strategy to accompany the Polypill, using tests that are inexpensive.

The idea of the tests is twofold; to identify the sub-group of children who will benefit from the Polypill therapy and to establish a baseline of markers to later understand any cases, should the Polypill “stop working”

Blood tests

·        IGF-1

·        Serotonin

·        Free T3

·        Cholesterol LDL & HDL

·        Histamine

·        Inflammatory markers CRP and   IL-6

·        Potassium

I would also use the TRH stimulation test, except it is not available where I live and requires several blood draws.  It shows central hypothyroidism to be common in autism (as it is, interestingly, in fibromyalgia).

I am expecting any loss in efficacy of the Polypill to be accompanied by a surge in histamine and/or the easy to measure inflammatory markers, C - reactive protein (CRP) and Interleukin-6.

The trials would take place in winter (no pollen) and would exclude people with food allergies, digestive disorders, IBD, IBS, pancreatic enzyme deficiency etc.  The trial would be exclusively for early onset autism, no regression.

People with seizures would be very welcome and might form a separate subgroup within the test; I expect the incidence of seizure and epilepsy to be reduced by the Polypill.

Having created a trial based on children with elevated IGF-1, Serotonin, Free T3 and Cholesterol, I would then continue to measure all the above indicators on a monthly basis.

Assessing Success

Since the Polypill has several active ingredients, I would expect a marked reduction in autistic behaviours, based on any established autism rating scale.  I would expect parents, teachers and therapists to be really impressed by the effect.

Using the above screening biomarkers to select the trial group, I would hope to achieve a successful outcome in a great majority of cases.  This success rate has to be measured.  Perhaps the screening exclusions and biomarkers are too restrictive, or not restrictive enough.  If it was 100% effective, they should be relaxed; if it was 50% they should be tightened.

What intrigues me are the cases where the Polypill may stop working after a period of success.  If this is understood, it will be another step in understanding the dynamic nature of autism.  If the loss in effect can be correlated to an increase in histamine, in some cases, I will know what to do.  If in some cases CRP and IL-6 rise but histamine and serotonin do not, we would know that the immune system had been activated, but mast cells have not degranulated.  In these cases it would require the, currently under development, “Autism Toolkit”, to provide some immuno-modulatory therapy.

Just as abruptly as the Polypill might stop working in a child, I expect it will start working again, when the external stimulation (whatever it might be) has been withdrawn.

In children who have a permanent state of over-activation of their immune system, they should have sky high CRP and IL-6 and the Polypill will never start to work in the first place.  High inflammatory markers are seen in regressive autism, according to Ashwood, who is on my Dean’s List.

EMA

Having rationalised my objectives, I am finalizing my initial submission to the European Medicines Agency, to see whether the Polypill should remain Peter’s off-label curiosity, or become an Orphan Drug, to share with others.