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”.

 

 

 

Rats in the Basement - lab update #1

This may be only the 4^th post on this blog, but in the background research is actually quite far advanced.  A few hundred learned papers on, have there been any further epiphanies?

Well at the risk of sounding smug, I have to say yes, or least maybe.

 

When I started out in late January 2013, I knew that rats in the basement was not going to be an option; either my elder son would use them for target practice, or my wife would object.

My original plan was to rely on my powers of observation to guide my research and just draw on the pool of existing scientific research as needed to develop a plausible hypothesis, that could then be tested and quite likely rejected.  This is more like primary research, the fun type. I used to do a lot of this.  Primary research is used extensively in the business world and sometimes verges on espionage.

In primary research I now have two projects:

 

·         TRH and more specifically TRH analogs.  This looks very promising, but gets pretty complicated and there will be lots of citations.

·         Hypokalemic Sensory Overstimulation.  This may prove to be just a curiosity.

Secondary research is what most people do.  It is all about reading other people’s research and then either dutifully regurgitating it, or putting a new spin on it and taking it forward.  I used to this a lot and it can also be fun.  The interesting thing I learned is that two different people, or “expert” teams, could look at the same data and come to diametrically opposing conclusions.  This has great relevance to Applied Neurological Analysis, which as from post #1 is now officially known as ANA.
 

Researching TRH took me into the depths of research concerning a wide range of psychiatric disorders, addictions, epilepsy and even HIV-AIDS.  It also led me to read some much lighter weight studies that actually did have the word autism in them.  Then one evening, on Google Scholar, I was jumping between Hyperbaric treatment for autism and vitamin B12 injections and had about 20 windows open on my laptop.

 

Just as lithium-ion batteries can overheat and start smoking on Boeing 787s, it is also possible with your laptop.  Not wanting my research to be grounded, I picked up the pace.

 

I was reading a paper that was in effect junking the use of Methylcobolamin (Methyl-B12) injections in autism.  Then I saw that it mentioned a subgroup for which it appeared the therapy had indeed produced a measurable  positive effect.  The author hypothesized that in these children the B12 was somehow raising the level of Glutathione (GSH). A-Ha and what exactly is that?  All will be revealed in a later post.

 
This led to 2 developments:-
 

·         Open up an investigation into GSH

·         Note that sub-groups can exist in autism and so there just may be more to a “failed” clinical trial than meets the eye.

 
Having allowed the laptop to cool down, I did a trawl through the research on Omega 3 fish oil.  I am not a follower of Complementary and Alternative Medicine (CAM), but it turns out that its followers are big buyers of fish oil.

I used to take omega 3 capsules because I read they are good for your heart.  A friend recently asked us to pick up some special ones in London that are supposed to make your kid get higher marks at school.  It turns out that even my Mum used to be given cod liver oil and malt during World War 2.  I would have written “during the war”, but in many parts of the world, where you read this blog, it then raises the question “which one?”.

Having learned from my friend Colin, that you can actually be allergic to specific kinds of fish, I had discovered a few months back that I too have intolerance to farmed salmon and trout.  When I looked into what they feed the fish, I soon came to believe that this was a plausible cause of my symptoms.  So this means no more salmon and much less “natural” omega 3.  It turns out that some people are even allergic to the fish oil supplements as well, but thankfully not me.

I concluded that I have a ready use for a large batch of unwanted, long expiry dated fish oil, should I need one.  So I decided to add an Omega 3 to my secondary research and potentially add it to the primary research pile.  I do admit to starting with a sceptical bias.

As you can see, often you need both primary and secondary research for the same job, but for the moment at least, there are no rats in the basement.

 

 

P.S.

If a further dose of humour is required at this time of day, ponder the reaction of the Japanese airline executive from ANA (All Nipon Airways) who is googling to see how much PR he is getting due the Lithim-Ion batteries in his parked fleet of Boeing 787 Dreamliners. Colin will be famous in Japan, as he deserves to be, and the sales of fish oil will rise.