This blog mainly concerns personalized medicine, which is a therapy targeted to a specific person, or sub-group. Personalized medicine can include drugs, OTC supplements, diets and, importantly, non-drug medical therapies like vagal nerve stimulation. Some non-drug medical therapies were covered in previous posts and others will be covered in future posts.
The other part of the bigger puzzle can be called personalized education; anything from ABA to music therapy to what you do at school.
Eleven years ago, when starting with our first ABA consultant, just about his first question was “are you following any special diets or biomedical therapies”. He was clearly against such therapies, seeing them as a big distraction from the all-important ABA and Verbal Behavior (VB). He did indeed have a point, you do have to focus your attention on multiple tasks and avoid being obsessed with vaccines, gluten or candida, as some people appear to be.
ABA does have its limits, as our first ABA consultant found with his own son. In the case of severe autism it may well help a lot, but it usually is not enough. Rather ironically this ABA consultant eventually came back to me years later to ask about personalized medicine.
Some people report terrible experiences with ABA and, if these are genuine, I think there must be some terrible ABA therapists out there. We had very positive experiences with ABA consultants and our home-trained therapists.
Education
In the case of Monty, aged 15 with autism, he started with very personalized education and only much later, at 9 years old, did we add personalized medicine.
It is pretty clear than in cases of severe autism you need all the help you can get and so as to achieve a relatively good life (the palm tree by the beach, in the above graphic); you need personalized education and personalized medicine.
Education of typical children
For some years I was a school governor at an international school and so I got to know many different teachers, different educational systems and curricula.
When schooling kids with autism the choice is normally between mainstream school, special school or home schooling. In some countries home schooling is illegal.
Mainstream schooling varies greatly from country to country. Most active autism parents seem to be North American and they likely do not realize how lucky they are to have a pretty easy school curriculum, which lends itself to less able learners.
In some other countries the standard of maths and science is very much higher and school is really geared up to benefit the most able. Anyone of average ability, or below, very often gets left behind.
The level of selection in schools is also important and highly variable. In some countries kids get separated at age of 10-12 into those who are expected to do well and becomes doctors/scientists/ lawyers and those who will end up with vocational training rather than a degree.
In other countries you get a genuine mix of abilities all the way up through high school.
Poor Learners
I had a visit recently from a friend of mine who runs an organisation in Austria that tries to attract top achievers from university to spend two or more years teaching in the country’s worst performing schools, before starting their intended high-flying careers. It is part of an international group doing the same thing across the world. They seem to be doing well and the schools perform much better with their energetic young teachers.
What was interesting to hear was just how bad the standards are at some of these schools. A significant minority of 12 years old kids are functionally illiterate. One reason is that they have many immigrant children who do not speak German at home, did not speak German in Kindergarten and now sit in a class that is 80% non-native German speakers. The end result is that they cannot write a sentence in German, even though they might have lived all their life in Austria. So much for inclusion/integration.
Interestingly, my friend told me that in Austria, almost no one knows that Hans Asperger was an Austrian. I did not mention that some Americans are worrying about whether Asperger was a Nazi. Andreas Rett, another Viennese doctor, whose name was given to Rett syndrome by the English-speaking world 17 years after he described it in the German literature, is another forgotten Austrian. Rett actually was a Nazi, so I suppose some people will want to rename that syndrome, when they figure this out. Leo Kanner was really Austro-Hungarian, being born in Lviv. Kanner was Jewish, so definitely not a Nazi. So many Austrians connected to autism and yet nowadays the German speaking world contributes almost nothing to autism research. I will leave you to draw your own conclusions.
Back to education.
The top performers educationally are usually Singapore, where they practice old-fashioned education and Finland, where they follow a very enlightened non-pressurizing Scandinavian approach and where school starts at 7 years old.
The maths curriculum and the workbooks from Singapore are widely used by home schoolers around the world and I bought them for my son.
A suitable learning environment for someone with severe autism
In many developed countries education authorities believe that children with severe autism can be educated in both mainstream classrooms or in special education.
Given just how variable mainstream education is, we should not expect consistent results. For some children inclusive education will work well and for others it might be a disaster. A lot depends on what you are being included into and you have to be “includable”.
Small classes, with up to 12 kids, that include all abilities and only one special needs learner give the best chance of success, in my opinion.
Classes with 30 kids including 2+ special needs learners are a recipe for failure for all 30 kids.
Special education varies from large groups and a single teacher in some countries to tiny groups and where each child also has their own 1:1 assistant. There is no normal or typical special school. There are some very good special schools in the United States, but they must cost someone $100,000 a year.
Home schooling is only as effective as how good the “teacher” is.
Parents need to think long and hard about how to educate their child with severe autism and not assume the State will provide them a perfect solution. The better the education is for typical children, the greater chance you have of good special needs provision. Not surprisingly, special education is good in Scandinavia and terrible in most poor countries. One of Monty's assistants moved to Norway to be a special needs teacher.
Some people with severe autism will struggle to learn anything, anywhere. These people need personalized medicine or else their 15-18 years spent in “education” is just day-care and a prelude to institutionalization, perhaps with a nice name like a group home.
Personalized Education combined with Personalized Medicine
At the age of 8, after 4 years of intensive ABA-inspired intervention, Monty could not grasp the simplest elements of maths; I mean single digit addition or subtraction using the number line. Language and cognitive function appeared to be immovable barriers to progress.
December 2018 marks six years after starting personalized medicine, and I just learned that Monty’s grade for Maths this term is B+. He could handle the algebra and trigonometry in the end of term test, without any prompting from his assistant.
The addition of personalized medicine has had a transformative effect on cognition. This continues to surprise people even now. Equally encouraging is that Monty has taught himself to swim "properly", he has long been confident in a pool or in the sea, but now at school they go to swim in a full sized pool and get timed swimming laps. Today he was the fastest of two combined classes, that is something else that would not have been expected.
One autism Grandad we know regards Monty as "80% fixed", but "some problems will always remain"; that is quite a nice summary. It is all relative to what you know, this Grandad only knows really severe autism. I think many of the parents of the 1 in 40 now diagnosed in the US with "autism" would regard Monty as far from "fixed", but then their kids are fully verbal and have few challenges.
People with severe autism inevitably plateau at a low cognitive-equivalent age, but it does not have to be like that, if you can treat the underlying biology.
If you start by treating the biology and fine-tune brain function to the extent that is possible, then you should benefit greatly from all that costly personalized education, that you may or may not get someone else to pay for.
Conclusion
If you have a child with severe autism, life may become a huge challenge. There are all kinds of horror stories you can read about - I suggest you do not dwell on them. Everyone has options, whether to rely entirely on what you get for free from the State, or whether to apply other methods.
In a resource unconstrained situation, the best outcome is likely to come by combining personalized medicine with personalized education. I can only say that this combination has worked well for us. In terms of money, it has clearly cost much more than having a typical child, about twice as much.
If money is tight, start with personalized medicine.
People tend not to put a value on time, but for many time may be the greatest cost. You typically cannot leave a person with severe autism unattended and if they have a complicated schedule, somebody always has to be there and to be able to step in when something gets cancelled, or someone is off sick. If money is tight, start with personalized medicine.
Until the 1970s, medicine did have a strategy for people with severe autism. It was diagnose, institutionalize as a young child and forget. The Germans added their own variant to this. Having shut down all the big residential hospitals for mental conditions, there is now often a big gap in provision. Where do you put adult-sized people with severe autism? It may not be a problem for those who are docile, but what about those who are not?
Hi Peter, we started with personalized education when he was 3, called neurocognitive therapy, a milder ABA versión,less structured. Also valproate with risperdal at the same time. Now, he goes to mainstream school with an assistant.There are 4 teachers in the class that are the same year after year until high school.He is the only one with autism and there are 20 children in the class. He has one more year of primary.
ReplyDeleteThe school with high school is very nice and small and located in a forest area. Regarding memantine, I don't like this versión of my son,returned vocal stimming, repeating words, and increased sensation of pleasure that in my son is a great NO. I guess that my son's dopamine supersensitivity is from birth and risperidone aggravated the problem. Memantine adds fuel to the fire. He was in a tiny amount for 7 days and also taking BCAAs counteracting its effects. This was also for Aspie and Tyler.
Merry Christmas!
Valentina
Merry Christmas Peter, and to all the rest of you as well!
ReplyDeleteI hope next year will bring some great advancements, as this year has brought many small ones. It has also brought me a new job at a neuroscience department (nothing fancy at all, but I get straight access to PubMed) and the task to document all my findings as input for the medical board of a gene-related community. Not so bad for a person who never had a formal medical education.
Peter, you have been the best teacher ever, and not only regarding medical facts but also as a role model to how to approach this very special parenthood. Without your blog, it would have taken me years to dare "personalized medicine", if at all, and that would have been even more too late for my daughter.
As for the readers and co-contributors of this blog, I am so thankful that you are here. You make me feel less unusual when others call me "that very dedicated parent". I really think it's strange that not most parents do what we do.
Take care,
/Ling
Hello Peter and Community!
ReplyDeleteHope all is well as we get closer to Christmas. I was about to send a Christmas message to all, but I just found a paper I had to share before I do that.
Ionotropic and metabotropic kainate receptor signaling regulates Cl- homeostasis and GABAergic inhibition.
https://www.ncbi.nlm.nih.gov/pubmed/30570751
We haven't yet gone the Bumetanide route yet, but I know that NKCC1/KCC2 is of particular interest to the community, and this paper could be of interest.
NOW, I get to say I wish you Peter, Ling, Agnieszka, Aspie, Tyler, and all of my friends in the entire community a wonderful and very Merry Christmas, and of course, a 2019 in which we all get to see improvements in our kids.
I really believe that we will see some very exciting things in 2019, and I look forward to hearing about the successes of each parent as we get closer to our goals.
AJ
Hi Peter and All here
ReplyDeleteIn Poland we celebrate Christmas for two days, so I hope it’s not too late for season’s greetings to all the Community :-)
This paper caught my attention few days ago, not sure if it has been discussed here:
“Bumetanide for Autism Spectrum Disorder in Children: A Review of Randomized Controlled Trials.”
https://www.ncbi.nlm.nih.gov/pubmed/30501497
It is not a cutting-edge science, but it might be helpful to show it to the doctor to get bumetanide prescription as it was written specifically:
“to assist practitioners in making informed decisions by providing a single resource that summarizes the primary literature.”
“At present, no medication is considered first line for the treatment of ASD. Clinicians may wish to explore alternative options to treat ASD, such as bumetanide, or be able to respond to patient questions about possible benefits and limitations.”
The conclusion is odd, but what is important, it says that bumetanide may be useful in autism:
“Current evidence suggests bumetanide, with close monitoring, may be useful in patients with moderate to severe ASD when traditional behavioral therapies are not available or an irritability-modifying pharmacological agent is not required.”
Hi everyone!
ReplyDeleteHope you all had a very Merry Christmas and that Santa was good to all.
I found the following very recent paper of interest as it identifies (for the first time) that ghrelin receptors and oxytocin receptors can form a heterocomplex, and this can affect downstream oxytocin signaling.
A ghrelin receptor and oxytocin receptor heterocomplex impairs oxytocin mediated signalling.
https://www.ncbi.nlm.nih.gov/pubmed/30582955
Yet another piece of the enormous puzzle of ASD.
I'm very hopeful for 2019, and I believe we will see some very exciting things over the next year.
AJ
Hi Peter,
ReplyDeleteWe have been on one type of ABA or another since my daughter’s diagnosis at 2.5 years. We are now on therapist number 7, and I can tell you it’s the therapist not the therapy that makes the difference. Not that therapists 1-6 were bad, they were still making progress, however 7 is a true magician, the changes have been outstanding and I put it down to the fact that she is flexible in her approach and able to see when something is not working and adapt accordingly.
Just came across some very interesting research looking at exercise, interleukin-6, and belly fat (visceral fat) that should be considered when looking at implementing any hard interleukin-6 interventions.
ReplyDeletePress Release:
https://www.sciencedaily.com/releases/2018/12/181227111418.htm
Paper:
https://www.sciencedirect.com/science/article/pii/S1550413118307447?via%3Dihub
In a nutshell, this research suggests that fat loss from exercise is due in part to interleukin-6 signaling, rather than simply burning calories from the exercise itself. Obviously if you run an ultra-marathon you will lose some pounds, but this research shows that if you use an interleukin-6 inhibitor (such as tocilizumab), while on an exercise program, you will actually gain fat mass, rather than lose fat mass. IL-6 levels are obviously elevated in obese people as well as those with other systemic inflammatory conditions such as type II diabetes, so the way interleukin-6 works in healthy versus diseased people may be different. The researchers even suggested pursuing research whereby obese subjects might be given an IL-6 injection to lose weight.
This means that broad spectrum IL-6 inhibitors like tocilizumab might have metabolic complications with respect to their use as an autism therapy and that better drugs that differentiate between IL-6 signaling in the immune system and IL-6 signaling in fat tissue may be needed.
Last but not least, happy belated Christmas and New Years to Peter and everyone else who frequents this blog.
Indeed, il-6 is not the devil, its in fact beneficial in the right amounts and absolutely crucial.
ReplyDeleteI have an extremely rare mutation according to my 23andme genetic data which shows im prone to having LESS il-6. Which I found striking, since most of the herbs and stuff that 'felt beneficial'actually lower il-6 in most cases. However theres also other studies that multiple compounds can have both pro il-6 and anti il-6 effects, depending on who takes it, what deficience/disease they are fighting.
In fact, vitamin c can also increase or decrease il-6 depending on setup so to speak.
When you consider that the fever effect in autism is due to an INCREASE il-6 and subsequently PGE2 elevation on the brain.
Both il-6 and PGE2 can upregulate oxytocin receptors and I wouldnt be surprised if this is also the reason of the normalizing effect of autistic features.
Also a hangover from alcohol increases il-6 signalling. Now these are just ways of naturally bypassing the security gates in people with autism so to speak but it shows that immune-brain cross talk is real.
Poor response to endogenous il-6 is probably also a factor.
Heres another example, how increasing dopaminergic tone can increase il-6 sensitivity (atleast in fat cells):
Dopamine D2 receptor upregulates leptin and IL-6 in adipocytes.
https://www.ncbi.nlm.nih.gov/pubmed/29472382
Hi Peter and everyone,
ReplyDeleteHave you heard about or already discussed here L1-79, fast tracked by the FDA for treating core autism symptoms?
https://www.mdmag.com/medical-news/fast-track-designation-granted-for-l1-79-in-treatment-for-autism-spectrum-disorder
It's a a tyrosine hydroxylase inhibitor and not much can be found about it.
Here is a SpectrumNews article - sceptical in their typical way:
https://www.spectrumnews.org/news/skepticism-surrounds-autism-drug-given-fast-track-approval/
What is your opinion?
Hi Agnieszka,hope you and your son are well, my son would be a good candidate for this drug and would like to make my own trial as soon as possible, but it is not available yet, isn't it? Tyler, could you give us your opinion too?
DeleteValentina
I think I posted about the drug 3-6 months ago on this blog. I will try and dig it up when I have the time or else you can search my comments. It could be a very helpful drug for excessive dopamine if the peripheral side effects are not too much. I looked into it and from what I gathered it didn't look too promising because it will likely be prohibitively expensive for most people to the tune of costing tens of thousands of dollars or even a hundred thousand dollars a year just as the only drug for spinal muscular atrophy costs 750 thousand dollars the first hear and only had that thereafter. The company knows that some parents will pay anything to keep their child alive a few more years so they take advantage of this. Though drug development and the science that goes along with it is almost always a good thing, I have no doubt many parents of children with autism will have their desperation financially exploited to the extreme. Every drug company does that these days so for that reason I would not get too excited by this drug quite yet.
DeleteLike Tyler, one of the first things I did was check the price of the already existing version. At $300 a pill it does not look very interesting.
DeleteHi Agnieszka, I posted about this like 2 months ago I believe, but nobody seemed to reply.
DeleteI honestly have my concerns about TH inhibition though, dopamine is not the devil. Too little dopamine will literally make somebody stupid. In fact TH (tyrosine hydroxylase) loss is one of the reasons behind parkinsons disease.
When you consider you need dopamine to feel social reward along with oxytocin, you can see how this drug would be a big no-no imo.
Then again thats just me and I seem to have low dopamine in my social brain areas.
Thank you all. I thought I read all what was published here, but sometimes I don't remember even my own comments. There is such a lot of data in this blog.
DeleteI also suspect this drug would not be the best for my son, but was curious about FDA fast track status. Anyway, that price makes me stop complaining about the BHB salts costs...
Happy New Year to everyone!
Here is some interesting research on ERK signaling and long-term memory:
ReplyDeletePress Release:
https://www.sciencedaily.com/releases/2018/12/181227102109.htm
Paper:
https://www.cell.com/cell-reports/fulltext/S2211-1247(18)31768-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124718317686%3Fshowall%3Dtrue
This study was done on fruit flies, but what I found interesting and possibly relatable to autism is that in autism you often seem to have a state of hyperplasticity and some research suggests in some animal models of autism this is due to a reduction in ERK1 relative to ERK2.
In this particular study they showed that the optimal period of spaced learning for maximizing ERK dependent long-term memory in fruit flies was to do 10 learning sessions spaced out at 10 minute intervals. This caused the fruit flies to retain what they learned for at least 7 days (a long time in the life time of a fruit fly).
Now of course if ERK signaling is already compromised, as they showed in this research, and what also seems to be problematic in autism, then what can be done to maximize learning as an alternative? Well, the researchers also found that massed learning which was optimal at 38 consecutive learning sessions also did the trick via an alternative learning process called Anesthesia-Resistant Memory or ARM for short. Previous research suggested that massed training did not incur a long-term learning benefit, but what they found was that you just needed to do a lot of it to make memories stick.
Now I am sure many people here have heard of spaced repetition learning, especially in the form of software many people use to memorize the kind of information you might put on flashcards such as law facts for when studying for the bar exam, or medical facts when studying for the MCAT. Software that comes to mind for those purposes is Anki and Supermemo. That particular category of software takes advantage of the spacing effect:
https://en.wikipedia.org/wiki/Spacing_effect
and ERK dependent learning seems to be involved in that type of learning. This means, for a normal healthy person with no ERK related learning disability, it is much more efficient to learn large amounts of information utilizing the spacing effect because you can learn more information in less time since you will need to study each piece of information many less times than you would have with massed repetition which is less efficient per study session in causing the brain to remember information long-term.
Now if ERK1 signaling is reduced, this means there is going to be a problem in getting memories to stick as synapses become hyperplastic due to ERK2 signaling increasing as an effect (ERK1 is the brake to learning and ERK2 is the gas). Here is one paper that explains sort of what I am talking about:
https://www.nature.com/articles/npp201413
So this fruit fly research suggests for people with ERK related learning disabilities (perhaps many people with low-functioning autism), that the best method of learning may be massed repetition which obviously is the method traditionally used in the recommended 40 hours a week model of ABA that has been promoted for decades. In other words, it may be that some people with this type of intellectual disability are capable of learning many things, just it will take four times as many learning sessions as a normal person (if you generalize from this fruit fly research) and that the intellectually disabled person will benefit very little from spaced repetition (i.e. review). Of course keeping someone who is learning disabled attentive and on-task consecutively for learning sessions four times as long as a normal person is no easy job, but it shows if there is a will there might be a way.
ohh such a useful fruit apple....i don't know the apple is used in such different manner in medicine also.Thanks for sharing the information
ReplyDelete