NICE Brits 281 and Californian Quacks 305?

I have to thank Paul Whitely  for a post on his website that I am hijacking today.  Click on Paul’s name to go to his blog.

National Institute for Health & Care Excellence (NICE)

NICE is an organisation in the UK, funded by the Department of Health.  They produce excellent guidelines on  most medical conditions for both doctors and patients.  They are all available free on line.

NICE & Autism

NICE are producing a guideline called:-  

Autism, The management and support of children and young people on the autism spectrum.  The guideline is still in the draft stage, but there are two versions:-

Full version (790 pages) 
Summary (40 pages)

You may wonder who on earth is going to read a 790 page document.  The 40 page document does not say a lot, you could summarize it as folows:-

•  Carers (parents) are unsupported, miserable and financially strained

• Children should have access to care and therapy, that does not currently exist

• Local autism teams should have the skills to provide, or organize, the interventions and care recommended in this guideline, but they currently do not have these skills.

• No magic cure exists

 

The NICE list of Dos and Don’ts  (Mainly Don’ts)

DO NOT:-

Do not use the following interventions for the management of core features of autism in children and young people: 

·         antipsychotics

·         antidepressants

·         anticonvulsants

·         exclusion diets (such as gluten- or casein-free diets)  -  sorry Paul

Do not use omega-3 fatty acids to manage sleep problems in children and young people with autism.

Do not use auditory integration training

Do not use the following interventions for children and young people with autism in any context:  

·         secretin

·         chelation

·         hyperbaric oxygen therapy 

DO:-

Consider a social-communication intervention for the management of the core features of autism in children and young people. For pre-school children consider delivering the intervention with parent, carer or teacher mediation. For school-aged children consider delivering the intervention with peer mediation.

Consider the following for children and young people with autism and anxiety who have the verbal and cognitive ability to engage in a cognitive behavioural therapy (CBT) intervention:  

·         group CBT adjusted to the needs of children and young people with autism

·         individual CBT for children and young people who find group-based activities difficult.  

For behavior that challenges, try antipsychotic medication.

  

The 790 page version  -   NICE Brits 281 and Californian Quacks 305

I was rather disappointed by the 40 page version of NICE, so I opened up the 790 page version.  I recommend you do too.  It is totally different.  Some people have spent many 1000’s of hours analysing all the scientific literature on a wide range of biological, social, psychological and educational aspects of autism.

The problem was on page 281.  This is the page where those clever guys over at Stanford 94305, get their research into Glutathione (GSH) mentioned. (94305 is their zip code) 

Then on pages 389/390 NICE give their verdict on the Stanford guys' findings.  They conclude that while NAC does nothing bad, it also did nothing good.

 

Now, I am no medical genius, but nor am I a complete moron. I read the full Stanford research paper as a highly sceptical, but informed, parent. I concluded, as did the Stanford team, that they had found something very important. To get the full report you have to pay $31.50 but I figured it was well worth it. So if this excellent research just gets sliced and diced, and then trashed, in this 790 page review, how much faith do I have in the other 787 pages?

I am with those Quacky Californians on this one.  Those NICE Brits can call me a quack too.

Always Show your Workings? More about Glutathione (GSH)

It may be a long time since you were in school, but you will most likely remember the maths teacher kept telling you to show your working.  The idea was that you might have got the method right, but got the wrong final answer; at least you could get half a mark.

I just asked Ted (aged 12) what happens these day at school if you get the right answer, but the workings were wrong.  Ted debated this with friend, whilst continuing to play a video game together.  The conclusion was that if the answer was right, but the working was wrong, you would not get full marks. 

In the field of autism this seems to be a recurring scenario (right answer, but wrong workings).  Somebody finds a therapy that appears to work, and produces some scientific justification, but then along come other clever people and use science to tear apart the proposed justification (or workings).

Yesterday while adding tags to this blog, I came across a blog with a delighted parent, who had noticed a dramatic reduction in autistic behaviours in her child.  I paid attention because it mentioned the word Glutathione.  The post went on about the child having low levels of Glutathione (GSH), because of “unregulation of CBS(++)”,  and the Yasko genetic panel.  What is all that about, I wondered.

Using Google I quickly found two avenues to pursue, in no time at all:-

• A very fancy website with colour charts, fancy names like "Neurological Research Institute",  Genetic Profiling Systems,  and "A guide to nutrigenomic testing".  Then alarm bells started to ring; a Dr Amy Yasko of Holistic Health International, who can sell you nutrigenomic testing for just $495.

• A very basic website,  with a paper called “CBS Upregulation, Myth or Reality". This paper by Mark London, from MIT, seems dedicated to refuting the “science” put forward by Dr Yasko.  London concludes:-  

“Thus, while some of the aspects of Dr. Yasko’s treatment plan may have usefulness, there is no support that CBS upregulation can have any negative effects.”

 
Then I find quickly in blogs, that people are wondering just who is this Mark London and what interest has he got? Maybe he does not like Dr Yasko?  It turns out that after the $495 nutrigenomic testing, you then have to buy something called the “Ammonia support supplement”.  I checked her site and just 24ml will set you back $85, it say that is enough for 48 servings and you need 3 servings a day. So that about $5.30 a day or nearly $2,000 a year.

It looks like Mr London thinks that’s a lot of money to pay, without showing the correct working.

I have raised my son’s Glutathione (GSH) and it cost me 20 cents a day or $73 a year.  I am with Mark on this one.

 

Glutathione(GSH)  Part I

Glutathione (GSH)  Part II

Glutathione (GSH)  Part III

 

Aspirations vs Expectations

A couple of years ago, I came across a very useful paper that helps deal with that nagging question all parents of autistic children probably have;  that question is of course what will the future bring?  The paper is called Counseling Parents Regarding Prognosis in Autistic Spectrum Disorder.  It is only three pages long and it is free to download.

It is written by a very experienced Neurodevelopmental Paediatrician called Dr James Coplan, naturally he is an American.  He has an excellent website and he has his own channel on YouTube.  There are 4 short videos about the history of treating autism and one quite heavy one about challenging behaviors in autism.  In one he comments that autism is 130 years behind most areas of medical science.  He certainly knows his stuff, but he is not a researcher like us. 

 

Coplan applies four premises:-

1.    Atypicality (how autistic you are) occurs along a spectrum from mild to severe.

2.    The observed severity of autism in the same individual varies with age.  Many children with ASD do experience significant improvement over time.

3.    ASD of any degree of severity can occur with any degree of general intelligence.

4.    The long term prognosis represents the joint impact of ASD and their cognitive ability; higher IQ leads to better outcome.

The ideal outcome is for child B, whose atypical symptoms were always mild and whose intelligence is average or better.  The core features of ASD break up into fragments, which diminish in severity with the passage of time.

A less favourable outcome is child A, who has severe autism, plus mental retardation (MR).  As time goes by, he continues to exhibit the same level of autism, plus MR.

Clearly most children will be somewhere in between child A and child B.

 

Aspirations

I learnt from using ABA (Applied Behavioural Analysis) that it is always important to aim high, but not so high that your child is going consistently to fail.  If you aim low, you are certain not to achieve much; it is common sense really.  Every day raise the bar slightly and as the months go by, you will surely see progress.  If you are too ambitious, the child will get too used to failure and your efforts will be counter productive.

Expectations

I think it is best to leave the expectations to Dr Coplan and his framework.  Dr Coplan seems a bit fatalistic, he says that there is little evidence that the prognosis today is different to that in the 1970s or 80s. 

In my opinion, the tools available to parents today are far beyond the wildest dreams of parents in the 1970s; you just have to reach out, take them and apply them.  Rather than accepting a mediocre prognosis, do something about it.

 

 

Glutathione (GSH) Part III - Say Goodbye to Obsessive Behaviours

Stereotypy is a word you may never have used, but it is there in the dictionary.  In the world of autism, they made up their own word for it; “stimming”.  Stimming does not appear in the Oxford English dictionary, but here is a nice definition from Urban-dictionary.

Stim, stims or stimming is short for "self-stimulation". Almost everyone does it (tapping feet, cracking knuckles, twiddling thumbs), but in autistic people these behaviours are more pronounced and may seem downright strange.

Stimming is an obsessive behaviour that can get in the way of doing anything else.  If you are wiggling your fingers 10 cm in front of your eyes, not surprisingly, you are lost to the outside world.

But there are plenty of other obsessions; here is an eclectic mix:-

·         Tearing up papers into tiny pieces

·         Jumping, rocking, trampolining

·         Roller coasters

·         Thomas the Tank Engine

·         Watching the same part of a cartoon over and over again

·         Going to the theatre

·         Eating a Big Mac every day for lunch

·         Always following the same route, walking to the park

Using behavioural techniques from ABA, you can go a long way to managing, and then dramatically reducing, these obsessive behaviours.

Now, thanks to some science, it seems that these obsessions can finally be got fully under control.

By implementing a program to increase GSH using NAC, the science of which was outlined in Glutathione (GSH) Part II -N-Acetylcysteine (NAC), we have witnessed a near immediate cessation of uncontrollable obsessive behaviours.  The obsessions remain, but they are now firmly under self-control.

 

"Curtains close"

Glutathione(GSH) Part I

Glutathione (GSH) Part II

 

 

 

 

Nela and the Magic Flute

Nela is Monty’s excellent assistant at school, but today, because he is a bit sick, she came to Monty’s house instead.  Nela also has her own theatre school, which she runs in the afternoons.  Monty loves the theatre, and the curtains in particular.

Shortly after Nela arrived at our house, she said “Monty is going to see the Magic Flute”.

So how did Nela know that Monty is going to the opera (albeit the children’s version)?  Well, Monty told her, of course.  Now this might not sound much to you, but for me that is worthy of a big WOW.  Autistic kids are not big conversationalists at the best of times.   Even stranger, said Nela, was that he was really talkative all morning.

Now when his brother Ted is sick, it is about the only time he ever stops talking.

Then I said to Nela, actually it’s not strange at all; it is a proven fact that when autistic kids have a temperature they behave more “normal”.  I said that I would write about in my blog, so now I have to. I was actually saving this for a later post, when I set out the “Peter hypothesis of TRH induced homeostasis in autism”.

 

The post I originally intended to write

But, first a quick detour.  For those serious scientists among you, there is an excellent blog that you should take a look at.  It is written by a professional autism researcher, Paul Whitely.  The blog is called Questioning-Answers.

Now, late last night I was looking at Paul’s blog and reading all about something called tetrahydrobiopterin (also known as BH_{4 ,}THB, trade name Kuvan, or even sapropterin) and how it might be a useful drug to treat autism.  Then I looked at his links to the research papers and then I looked at the citations listed in those papers; it looked like another long session on Google might lie ahead.  Then, I concluded that since people have been talking about BH₄ and autism for 24 years; somebody should have done a serious controlled study by now.  So I will wait until they do, before getting out my textbooks.  Actually, by reading the label (the citations at the bottom of the study) I saw the following at number 53:-

 

53.  Klaiman C, Huffman L, Elliott GR. Sapropterin as a treatment for Autism Spectrum Disorders: a double-blind, placebo-controlled trial. J Child Adol Psychop 2013 (in press).

So after 24 years, it looks like someone has finally done a serious study.  I expect in a month or so it will appear on Paul’s blog, then I will take a good look.

Back to the Opera

So as not to disappoint Nela, let’s get back to business.  When I started this blog I was going to match my observations of Monty’s quirky behaviours to some solid science.  One observation was that whenever he stayed home sick, he was always great at his piano lesson, and with me on Whizz.com, the maths program, or doing literacy/numeracy with his assistant.

So applying some ANA, I found that the American Academy of Pediatrics (Americans spell it like that) had published a study called:-

“BehaviorsAssociated with Fever in Children with Autism Spectrum Disorders”

They concluded that it is indeed true; a fever makes you less autistic; but why ?

They put forward five possible reasons:- 

(1)  neurobiological effects of selected pro-inflammatory and/or anti-inflammatory cytokines, which have been found to be increased in cerebrospinal fluid (in the absence of fever) and postmortem brain tissue of individuals with autism and may be generated during different phases of responses to fever,  

(2)  modification of neuronal and synaptic function secondary to variations in body temperature that influence neural conduction velocities or synaptic transmission,  

(3)  modification of dynamic neural networks as a result of changes in cellular signal transduction and gene transcription that regulate synapse formation and function, 

(4)  increased production of other stress-related proteins, such as heat-shock proteins, during fever that might modify energy consumption and mitochondrial activity  

(5)  stimulation of the hypothalamic-pituitary-adrenal axis leading to modifications of neurotransmitter production and interaction.

 

And noted:- 

Should any of these mechanisms be proved to effect behavior changes in individuals with ASDs, this would stimulate research on potential treatments focused on these pathways.

Well this was another of my Eureka moments, since reason (5) fits very neatly with my TRH hypothesis, which was again based on other observations of Monty’s behavior.

For now, at least Paul and Nela will be intrigued; the rest of you may be bemused.  All will be revealed shortly, when my I finish my TRH project.

Now, as Monty would say,  “curtains close”.

 

 

 

Great Minds Don't Always Think Alike

Today’s post may appear to be just ramblings, but rest assured it is another necessary piece of our jigsaw puzzle.

What do you think I have in common with the President of the United States?

A.    Peter and Barack are fans of the Discovery Channel show, Myth Busters

or

B.    Peter and Barack had a drink with both  Michael Bloomberg and Vladimir Putin

It was a trick question.  The answer is (A) and (B).

For those of you who do not have Discovery Channel at home, Myth Busters is a hit TV show filmed in San Francisco, where Adam Savage and Jamie Hyneman set out to test popular myths, to see if they are plausible, confirmed or busted.  Adam and Jamie worked in the Hollywood special effects industry, but they have very unusual backgrounds.  They have a great approach to testing myths/hypotheses and always start with an open mind.

If Adam and Jamie were to join us on our quest – they would probably call it a crusade – we would have valuable support indeed.

Cold calling and networking in Business, but not in Medical Science

Now I could write a book about cold calling and networking in the business world.  If you have a bright idea, you can use it to open doors in most parts of the world.  Like most things, it works best in America, but it even worked well in some former communist countries, just a few years after the Berlin Wall came tumbling down. Romania is a good example, still in my 20s, I managed to get one to one meetings with important people, including with two of the five richest people in the country.  From my flat in Kensington, I got summoned to meet Lord Rothermere, the last of the great English press barons, to discuss an idea.  The list goes on.

But either I have lost my magic, or it just does not work on doctors and medical researchers.  They are not interested to talk to me, I find this quite perplexing.   Maybe I need a white coat?

They seem to be very closed-minded, or just not interested in autism.  Even American researchers are not interested!  Even when they are working in the field of neuroscience.

I think the medical world needs some kind of shock from the real world.  It seems, at least in case of polio and malaria, they are getting just that.

 

Bill Gates, Paul Allen and Peter (me)

Next cryptic puzzle; what do Bill, Paul and Peter have in common?

Well, you surely know that Bill Gates is the man behind Microsoft.  You may not know that Paul Allen is the co-founder of Microsoft.   Paul also set up the Allen Institute for Brain Science, which he and his sister endowed with $100 million.

Now Bill Gates is applying his business acumen (and not inconsiderable fortune) to eradicating polio.  If you want some inspiration just listen to Bill talk about how he is going about eradicating polio.  He is applying business common sense, rather than any medical knowledge.  He is making great progress.  If you live in the UK you can watch the full 60 minute lecture on the BBC iplayer just search:-   Bill Gates: The Impatient Optimist - The Richard Dimbleby Lecture. If you do not live in the UK you can only watch access the short preview on YouTube.

There is so far only a very weak link between Peter and Paul.  Before starting this blog, but after watching Bill talk about polio, I wrote to Paul.  In essence, I said go talk to those French research guys about Bumetanide and put your millions to good use.  Well at least I got a polite reply from the Institute.

I have not met Bill;  maybe one day I will.  It turns out that Mike (Bloomberg) and Bill are now joining forces to eradicate Polio.

By the way, in case you did not know, Mike is Mayor of New York and founder of Bloomberg LP a leading global provider of financial data, analysis and news.  He is also a great guy (and my former client).

Conclusion

Well, does all this really fit together?  I think it does.  We need a little something from the Myth Busters (Adam and Jamie) and some more from the philanthropists (Bill, Paul and Mike).  I think it’s called inspiration !

As for Vladimir, well Barack might not agree, but I think he is doing a pretty good job over there in the Kremlin.

до свидания

 

The Holy Grail - and where to find it

If you were are a 12 year old boy, like Ted, who loves watching the History Channel, you would know all about the Holy Grail.  Depending on your religion, you may know it as a sacred cup linked to certain important Christian events; but there are also Celtic myths about a cauldron with magical powers.  Throughout history, people have been searching for the Grail, from King Arthur to Indiana Jones.

This blog is itself a search for the Holy Grail.

Monty is a big fan of a well-known picture book series called Meg & Mog.  It is about a nice witch called Meg and her black cat called Mog.  Featured prominently is a magic cauldron, which Meg uses to cast her magic spells.  Just click on the above link and all will become clear.

So, we are looking for the Grail

Well, if you have struggled through all of this blog from the begining, you already know where to start looking.  California looks pretty hot, but then again there are some rumours about somewhere in France.  All will be explained, as we proceed further.

Homeostasis

First we need to learn a new word, Homeostasis, if you already know what it means, you are much brighter than me.

Do not confuse it with Homeopathy.  There may be another coincidence here as well.  Those generous people at Wikipedia give us this definition:-

Homeopathy  /ˌhoʊmiˈɒpəθi/ (also spelled homoeopathy or homœopathy; from the Greek hómoios- ὅμοιος- "like-" + páthos πάθος "suffering") is a system of alternative medicine originated in 1796 by Samuel Hahnemann, based on his doctrine of similia similibus curentur ("like cures like"), according to which a substance that causes the symptoms of a disease in healthy people will cure similar symptoms in sick people.  Scientific research has found homeopathic remedies ineffective and their postulated mechanisms of action implausible. The scientific community regards homeopathy as a sham;  the American Medical Association considers homeopathy to be quackery,^]and homeopathic remedies have been criticized as unethical.

Now let’s get back to Homeostatis and to help us really understand it, I decided to give a detailed example using the medical condition diabetes.

Homeostatis is a process through which the body's internal environment is kept stable.  For example, when the level of sugar in your blood is too high, your body detects this, an alarm goes off and the body acts to reduce it; conversely when blood sugar is too low, again the body detects this and sends a signal to raise it.  All this happens 24/7 and you do not even need to think about it.  That is, unless you are diabetic.

So we have:-

·         A  receptor, like a tiny sensor that is constantly measuring blood sugar.

·         Positive feedback, when the receptor detects a low level and then tells the body to raise the level of sugar 

·        Negative feedback is when another receptor alarm goes off, and the body needs to lower the level of sugar in the blood. 

·        Homeostatic imbalance occurs when the body is overwhelmed and can no longer regulate itself and regain stability.  Many diseases are indeed the result of such an imbalance; diabetes is but one.

Insulin is the principal hormone that regulates uptake of glucose (sugar) from your blood.  Insulin is released into the blood after eating.  Insulin is also the principal control signal for conversion of glucose to glycogen, for storage in your liver (and muscle cells).

Lowered glucose levels result both in the reduced release of insulin and in the conversion of glycogen to glucose. This is mainly controlled by the hormone glucagon, which acts in the opposite manner to insulin. Glucose is forcibly produced from the liver (where it had been stored as glycogen) and enters the bloodstream.

Both insulin and, its opposite, glucagon are produced in the pancreas.

Summary

So we have a receptor constantly measuring your blood sugar.  You eat a chocolate bar, blood sugar rises fast, an alarm goes off.  Release the insulin !  Insulin is released from the pancreas.  Remove excess glucose and store it (as glycogen) in the liver !  Blood sugar level is falling. Homeostatis restored; panic over.

Then you go for jog in the park.  Receptor detects falling blood sugar.  Release glucagon !  Glucagon is released from the pancreas.  Go to the liver and tell it to start converting glycogen back to glucose !  Blood sugar level is now rising.  Homeostatis restored, panic over.

Back to Ted and the quest for the grail

Ted sometimes finds it hard to explain what Dad’s job really is;   he is not the first to ponder this.  Now, Ted has decided that his Dad can officially be described as a wizard.  This helps me a great deal with this blog. 

We will now opt for the pagan Celtic myth about a cauldron with magical powers, this will be our Holy Grail.  We just need a cauldron, a wizard, some ingredients and a magic spell.  We are nearly there.

We even know part of the spell:- “ homeostatis and channelopathy  .........”

A final few words

In our first two weeks of this blog, we have been busy travelling.  We started in France, went all the way to the Punjab to meet a clever chap called Baldeep in  Chandigarh.  Then we headed over to Palo Alto in California.

The good news is that back at Monty's house, the cauldron is bubbling and the magic already seems to be working.  We just lack a few more ingredients and that elusive spell.