Pentoxifylline and cGP (an IGF-1 normalizer) from Blackcurrants, for Autism?

 

 

Readers may be wondering at what point Peter will run out of things to write about.  I do sometimes wonder the same thing. I was going to also write about Loperamide (Imodium), but the post would have been too long. Next time!

Pentoxifylline

Pentoxifylline has been in use to treat autism for 50 years. The original studies did suggest its effect was greatest among small children.  I have been in some discussions with a US psychiatrist, Dr Powell, who is a big fan of the off-label use of this drug to affect the brain in adults.  He has even written a book on the subject.

My previous posts on Pentoxifylline can be found here: 

https://www.epiphanyasd.com/search/label/Pentoxifylline

Dr Powell’s patients with autism tend to be older children, not the toddlers who did well in clinical trials in Japan in the 1970s.  He sees significant improvement in many, but not all, of his patients with autism.  The parents report improved social interactions and having higher-level discussions with their child.

What is notable is that he uses frequent dosing, 4 times a day, always after food to avoid the GI side effects.

Pentoxifylline is inexpensive, but its effect does not last long, hence the frequent dosing.  Some people take taking this drug 5-6 times a day.

Pentoxifylline has multiple modes of action, it should increase blood flow to the brain and it is broadly anti-inflammatory.  It is a non-selective PDE inhibitor, normally used treat muscle pain in people with peripheral artery disease. It increases red blood cell flexibility and it reduces the viscosity of blood.

There are PDEs 1 to 11. It all gets quite complicated, for example PDE1 subtype A2 has a potential role in neurodegenerative diseases, including:

·        Parkinson's disease

·        Axonal neurofilament degradation

·        Motorneuronal degradation

·        Neuronal ischemia

·        Alzheimer's disease

·        Epilepsy

Recall that PDE4 inhibitors are used to treat asthma and COPD. We can potentially repurpose those to improve myelination in MS, or autism, and at specific low doses they can improve cognition.

 

cGP (from Black Currants)

I did write quite a lot in this blog about growth factors and autism.  The familiar ones are BDNF, NGF and IGF-1, but there are many more. 

My previous posts on IGF-1 can be found here: 

https://www.epiphanyasd.com/search/label/IGF-1

We know that growth signaling in autism is disturbed, but it is not simple.  As the disease progresses (the fetus develops, the baby is born and grows into a toddler) the imbalance in growth signaling changes.  This means that what would be helpful in a 6 month old baby might well be inappropriate in a 6 year old.  This is a good example of what I call the what, when and where of treating autism. Here it is the “when” that matters.

Some people lack BDNF while others have too much. Very possibly, this changes over time in the same child.

One possible therapy for autism is injections of IGF-1 (Insulin-like Growth Factor 1).  IGF-1 plays an important role in childhood growth.

A synthetic analog of IGF-1 is used in children for the treatment of growth failure.  This drug called Mecasermin was used in autism trials and in Rett syndrome trials.

In Rett syndrome the search has been on for an oral therapy.

Trofinetide (NNZ-2566) is a potential therapy for Rett syndrome being developed by Neuren Pharmaceuticals in Australia.

Trofinetide is derived from IGF-1.

Trofinetide got to phase 2 trials as a therapy for Fragile-X in 2015.

The second product in development at Neuren is NNZ-2591.  It is aimed at normalizing the level of IGF-1.

This is in the pipeline to treat:

• Phelan-McDermid syndrome (Shank3 gene and others not working)
• Angelman syndrome (UBE3A gene not working)
• Pitt Hopkins syndrome (TCF4 gene not working)
• Prader-Willi syndrome (MAGEL2 gene and others not working)

https://www.neurenpharma.com/irm/content/product-development-pipeline.aspx?RID=483&RedirectCount=1

 

What is NNZ-2591?

It is an analogue (modified version) of cyclic glycine proline (cGP)

Cyclic glycine-proline (cGP), a metabolite of IGF-1, is neuroprotective through improving IGF-1 function.

There is also research focused on Parkinson’s and Alzheimer’s where it seems that cGP is reduced.

In New Zealand they found that supplementation of Blackcurrant anthocyanins (pigments) increased cGP in the spinal fluid of patients with Parkinson’s.

This also led the way to the idea of increasing cGP as means of protecting the brain during aging. There is now a commercial OTC product in New Zealand to do just this.

Our reader Daniel, who has a daughter with Rett syndrome, is assessing the benefit of cGP, using the OTC product cGPMAX. The results so far are promising.

Rett is very specific because we know for sure that IGF-1 and NGF are disturbed.

Is cGP going to be beneficial in broader autism?  May be yes, but we come back to the what, when and where.  It may well depend on when a specific person takes it.  We have both hypoactive pro-growth signalling autism and hyperactive pro-growth signalling autism.

 

 

Unfortunately, what the clever researchers who came up with the above concept did not consider is that you may start out hyper in the womb and switch to hypo a few short years later.

  

Conclusion

Frequently dosed Pentoxifylline looks like a potentially interesting therapy for many with autism, including some with high IQ.  Take note our Aspie readers.

Daniel’s idea to look at the Neuren’s non-Rett therapy as a Rett therapy is interesting.  In effect you do not need to wait for the Australian drug, you can hop across the Tasman Sea to New Zealand and use their cGP supplement, developed for protection against dementia.

You would also think that parents of children with:

• Phelan-McDermid syndrome (Shank3 gene and others not working)
• Angelman syndrome (UBE3A) gene not working)
• Pitt Hopkins syndrome (TCF4 gene not working)
• Prader-Willi syndrome (MAGEL2 gene and others not working)

might want to follow Daniel’s lead.

As you can see, there is a lot of trial and error in science.  Back in 2009 NNZ-2566 was in clinical trials for the treatment of cognitive deficits following traumatic brain injury.  That must not have worked out.  Fragile-X did not work out and now it is phase 3 for Rett girls, which seems to be going well.

 

IGF-1 for old people

The same growth factor IGF-1 that is key during development also plays a key role in aging. Dr Jian Guan made a world first discovery. She discovered that cGP (cyclic Glycine-Proline) was responsible for controlling the IGF-1 hormone in our body. Thus by increasing the level of cGP in our body, the cGP will essentially command the IGF-1 to build more blood vessels.

Dr Jian Guan, was then recognised as the world-wide authority on cGP. In 2017 she discovered that New Zealand blackcurrants contained high volumes of natural cGP which could regulate optimum levels of IGF-1 in the body.

So now we have Antipodeans/Kiwis fending off dementia, and potentially metabolic syndrome, by taking their locally made cGPMax.

Will it help you case of autism? Who knows, but if it does not, just give the leftover pills to Grandma, Granddad or take them yourself!

 

All the supporting papers from New Zealand.

https://cgpmax.com/pages/our-science

 

More Politics of Autism, the NCSA, Prader Willi, Happy Puppets and the Crazy Car Wash

Kempton Park Racecourse, near London - now known for its Hot Dogs

A science-heavy post about microglia is in the works, but today’s post ties together some less complex issues.

As I mentioned in an earlier post, there is a new book out called the Politics of Autism, by Dr Siegel.

I did buy 2 copies, so I could give one away. It is a bit heavy going and I did skip some parts, but it is as expected a good read. The author does personally know/knew some of the “big names” in autism like Lovaas and even Bernie Rimland.

I was interested to read that Lovaas basically cheated in his famous ABA “clinical” trial, where he showed amazing responses. All the trial participants that did not develop speech during the trial were “retired” during the trial. He rigged the result, by removing those less responsive to the trial therapy.  If you follow this subject, you will know that some Americans and Canadians get very upset when intensive ABA is not provided for free to their child, believing that it would likely "cure" their child, like in the Lovaas study. This trial is constantly used to support the idea of intensive early intervention producing dramatic life changing results.  In most people with severe autism, no amount of behavioural intervention is going to change the fact that they are severely autistic. It does though make many such people more functional, which can greatly help them. Expectations need to be realistic and parents should not feel guilty if they cannot provide many years of therapy costing $60,000 a year. You can achieve a great deal at much less cost.

Siegel thinks that Bernie Rimland (of ARI and DAN!) started out well and then went a bit dotty.

She makes excellent points about education.

She makes the mistake of venturing into the realm of medicine, which is clearly not her field and tells readers not to bother trying to treat the biology autism. 10 years ago I would have been mistakenly backing her up on this, but then I had my epiphany, thanks to reading about Professor Ben Ari’s small clinical trial of Bumetanide in 2012.

Who should buy the book?

This is not a feel good book, it is a very down to earth book that tells the story as it is, not the sugar coated version.

I thought this book would be good for people who study autism at University, like one of Monty’s assistants; she now has copy number two.

Many people with Asperger’s would likely hate this book and think Dr Siegel is a witch.

I thought most parents of people with severe autism probably do not want to hear more about how bad things are, but perhaps I was wrong. Dr Siegel provided one of her old posts as a guest blog post for the newly formed National Council on Severe Autism (NCSA).

Diagnose and adios - autism families deserve better

The NCSA is a new group set up to represent what used to be autism, before the diagnosis got broadened. They are really all about DSM3 autism, or what we called Strictly Defined Autism (SDA).

National Council on Severe Autism

National Council on Severe Autism (NCSA) Launches New organization will advocate "for those who cannot speak for themselves."

Horror stories or just telling it how it is?

Some people with mild autism seem to be very upset by what NCSA are advocating, but that is hardly a surprise.

Decide for yourself whether you consider the NCSA to be spreading horror stories, or just telling it how it is.

An attention-seeking UK daytime TV “celebrity” has a son with Prader Willi syndrome and he is regularly described as having autism.  Prader Willi is associated with an insatiable appetite which, if uncontrolled, leads to obesity; reduced IQ, impaired vision, behavioural problems and a bad temper. It is caused by an anomaly on chromosome 15, which causes a loss of function of some of those 600 genes.

75% of cases occur when part of the father's chromosome 15 is deleted.  In another 25% of cases, the person has two copies of chromosome 15 from their mother and none from their father. As parts of the chromosome from the mother are turned off, they end up with no working copies of certain genes

A similar mechanism occurs in Angelman syndrome, except the defective chromosome 15 is from the mother or two copies are from the father.

Angelman (AS) and Prader-Willi (PWS) Gene Region

People with Angelman’s have small heads and are not obese; because they are generally very happy, they are sometimes called Angels.  The condition used to be called Happy Puppet Syndrome, which apparently is not seen as politically correct these days. I should add the Prader Willi could be called “please lock the fridge syndrome”, because if you do not remove food the child may become severely obese before he/she is 10, develop type 2 diabetes, rapidly become insulin dependent and then have even bigger problems.

The Prader Willi mother is campaigning for disabled people’s rights, which is of course a nice thing to do; she is against abuse/trolling on the internet.  She recently revealed that at 16 years of age, her verbal, but obese son cannot wash or dress himself and no longer attends school regularly, because he has learnt that by having an early morning meltdown, the driver will refuse to take him to school. Like many teenage boys he would rather stay home than go to school.

The mother says she is concerned he is missing out on schooling.

I dare say Dr Siegel would ask what kind of schooling is this 16 year old getting? Perhaps learning to wash himself and dress should first be mastered.  In someone without severe MR/ID this is a matter of correct instruction and unlimited perseverance, by someone.

Dr Siegel could repurpose her blog post again, this time:

Diagnose and adios? Prader Willi families deserve better

The mother says she is thinking of putting her son into residential care. That sounds great, but who is then ever going to teach him to wash and dress himself and restrict his eating? If Mum cannot, why would some employee earning near minimum wage in a care home make a better job of it? What happens when he starts to need insulin injections twice a day, because obesity was not addressed?

Sometimes horror stories do not reflect the child, but how they are being cared for and all with the best intentions.  Most such parents need help, indeed it’s to be expected. This all could be solved by some home visits from someone like Dr Siegel.  More of these people do exist; our Greek-American ABA consultant would give very similar advice to Dr Siegel. Avoiding school would not be tolerated, regardless of any meltdown. Someone with an IQ>60 definitely can be taught to dress himself, even if occasionally a shirt goes on back to front.  Food has to be restricted.

Monty's morning assistant at school works with many other kids with autism and from what she tells me, it is clear that many issues repeat, even the publicity-hungry mother who ends up failing her own child. Since our morning assistant is writing a self-help manual for parents dealing with severe autism, I can imagine where my other copy of Dr Siegel's book is destined to go. At least my autism intervention library is being put to further use.

It should be noted that some autism mothers react very dynamically. We have one reader who identified a novel effective drug therapy for her child and is now trying to commercialise it, we have another reader who has inspired and funded research into what was a rarely studied genetic "autism". Parents react very differently to the challenge of raising a child with a severe disability, in some it brings out the best.  It is not just about having a high IQ, or a lot of money.

Some people cannot afford to pay for such 1:1 advice, but many might choose to, if they knew it existed. In many countries, like some provinces in Canada, families dealing with a disability are given substantial financial resources to help themselves. In Ontario there is currently uproar on the proposed $140,000 cap on free autism therapies per child. That is $140,000 more free money that we received. I recently calculated our total cost of autism up to the age of 16 and when converted into Canadian money it is $190,000. They should of course have different limits based on different levels of severity. In the DSM5 jargon you have 3 levels of need/severity and so you could have a low limit for level 1, since Aspies do not benefit from vast amounts of ABA, say $20,000 and a high limit for level 3, say $250,000. Then wait for the surge in (re)diagnosis of level 3 autism in Ontario.

            Diagnosing for Dollars (click, for Dr Siegel's take)

Many “horror stories” appearing on the NCSA forums likely could be avoided by applying personalized medicine, rather than cookie cutter medicine, or standard psychiatric medicine. 

Kids with undiagnosed genetic disorders 

I am not a doctor, but I do quite regularly get to play guess the undiagnosed metabolic/genetic disorder.  The latest one is what would cause deafness and hypertonia and apparently no other symptoms.

I recently read that US medical insurance generally will not pay for genetic testing for autism, because there are no therapies.

But yet there sometimes are, if you look.

Look at the recent comments in this blog about a child whose genetic testing revealed a problem with the KCNQ3 gene, which encodes the Kv7.3 potassium ion channel. You can look up Kv7.3 channelopathy, or just the KCNQ3 gene.

This is at least partially treatable just by using google and the excellent Genecards human gene database; both cost absolutely nothing.

https://www.genecards.org/cgi-bin/carddisp.pl?gene=KCNQ3

You can both activate and block this ion channel.  You will need one or the other.

Jobs for adults with Autism

You do quite regularly hear about how an IT company like Microsoft, or a big bank is actively recruiting people with autism. This always makes me laugh.  IT jobs for Aspies - yes of course, but autism?

People with DSM3 autism are not commuting to work reading the Wall Street Journal, or the Financial Times; but there should be things they can do.

Many years ago there used to be special companies set up to employ disabled people. This became not politically correct, for some reason.

Remploy is an organisation in the United Kingdom which provides employment placement services for disabled people. It is now a “welfare-to-work provider” finding jobs for disabled people, but for most its existence it directly employed disabled people in a number of factories, owned by Remploy itself, and subsidised by the UK government.  This was phased out at the start of the 21st century, under the prevailing view that disabled people should have mainstream jobs.

Sadly, many disabled people cannot hold down a mainstream job.

You might recall Andreas Rett (of Rett Syndrome), as well as being a doctor, established a factory in which neurologically disabled youngsters could work. That was 50 years ago.

One supermarket chain where we live sometimes has young people with Down Syndrome, or MR/ID helping to pack your groceries.

Monty’s afternoon assistant was telling me how sad it is that one Aspie her age is still without any job. My reply was that someone has to create him a job, just like we will have to create Monty a job.

I am a big believer in developing musical and other artistic skills, it did not get the above Aspie a job, but it does give him something to do.

Our very worldly Greek-American ABA consultant told me long ago that the biggest problem “her kids” face, as they grow up, is that they have nothing to do with all their time.  No job and no hobbies is not a good combination.

As I write this text, Monty is downstairs drawing a frog. Before that he was playing all the melodies in his current piano book.  Before that he washed his Mum’s car and earlier on we were washing my car.

Monty’s Crazy Car Wash

You gotta be a little bit Crazy to work here!

You gotta be totally Crazy not to try it!

I think Monty will end up more capable than having a car wash, but it is quite a suitable job for many young people with DSM3 autism. It is a genuine job, whereas packing groceries is not and the Crazy Car Wash is a lot of fun.

Good journalism?

There are very few journalists who are credible when they write about autism; they generally do not understand it at all (you cannot blame them for that!); then there are some Aspie ones, who will by definition tend to lack empathy, and they can completely fail to understand the severe end of the spectrum, often in a jaw-dropping fashion.

I rather liked this article by a 28 year old journalist taking charge of her 24 year old sister with autism, for the first time and going for a girls’ weekend riding horses.

https://www.telegraph.co.uk/travel/family-holidays/holiday-with-adult-sibling-with-autism-horse-riding-dartmoor/

I wonder at what point my 18 year son will be taking charge of his 15 year old sibling with autism, for a boys’ weekend. Hopefully I will not need to wait 10 years.

I expect it will be something eventful like Tom Cruise and Dustin Hoffman on a road trip to Las Vegas, in the excellent, but nowadays much maligned, film Rain Man. Bernie Rimland was the autism advisor for this film. 

This Christmas in London on December 26^th, Monty asked me if he was going to be having a hot dog for lunch; leaving me to ponder where did that idea come from. He accurately recalled that 12 months previously, on Boxing Day, he had gone with Uncle Stuart and Dad to Kempton Park for a boys’ day out at the horse races. The weather is usually cold and damp (i.e. miserable), but you do get to have a hot dog.

Conclusion

If you can take the sometimes brutal honesty of describing things as they really are, then Dr Siegel’s new book is going to be appreciated and you will also like the new US National Council on Severe Autism. 

A sense of humour will do you much more good than political correctness ever will. Upsetting people can sometimes be necessary to enable them to acknowledge their own delusions. I am beginning to sound like Dr Siegel, who likely would take her car to the Crazy Car Wash, should Monty open a branch in California.

It is up to parents to stop their child becoming obese, even more so when they have a genetic propensity towards this condition. 

If you do not have $60,000 a year to pay for ABA and feel you are missing out, make your own intervention program instead. Buy some books and recruit some helpers.  Don't spend years fuming in a waiting list, pondering what might have been.

.

It’s not Autism, it’s Sotos Syndrome – and more about GABA therapies

 Peter the wild boy, with Pitt Hopkins Syndrome

I recently returned from a 25 year class reunion; of the 200 or so class members about 120 turned up. Of the 200 we know that at least 5 have a son with autism and at least one has a nephew with autism.  So I had my first ever “autism lunch” discussing all those tricky issues we are left to deal with.

What was immediately apparent was how different each child’s “autism” was and that none of them were the autism-lite variants that are now being so widely diagnosed in older children. or even adults .  Of the six, two are non-verbal, one is institutionalized, yet one talks a lot.  Three sets of parents are big ABA fans and one child did not respond to ABA.

You may be wondering about that high incidence of autism.  This was not a gathering of science boffins or mathematicians; this was at a business school.  One thing is obvious, you can correlate some autism incidence with educational level.  You can connect all sorts of measures of IQ to autism, from having a math prodigy in the family, to having professors at Ivy league type Universities, particularly in Mathematics.  It does appear to be true that the so-called clever genes are also associated with some types of autism.

I presume that if my science-only university organized such events the incidence of autism would be even higher.

On the way back home we met an acquaintance at the airport, who was telling us all about his son with Sotos Syndrome.  "It is not autism", we were informed, but then I am not quite sure what is.  When you look it up, many of the symptoms look just like autism.  In fact, it is a single gene dysfunction that leads to gigantism and various elements of autism.

This brings me to the painting above of Peter the Wild Boy; it is not me I should point out.  The above Peter was a German boy who came to live in England in the 18^th Century; he was non-verbal and is now thought to have had Pitt Hopkins Syndrome.  Like Sotos, this is another very rare single gene disorder.

We have already come across Rett Syndrome, which for some reason is treated as autism.

Fragile X is thought of as a syndrome where autism can be comorbid.

Timothy Syndrome is fortunately extremely rare, but I have already drawn on it in my own research into autism.

There are also autism related disorders involving multiple genes.

Prader–Willi syndrome  is a rare genetic disorder in which seven genes (or some subset thereof) on chromosome 15 (q 11–13) are deleted or unexpressed (chromosome 15q partial deletion) on the paternal chromosome.  If the maternally derived genetic material from the same region is affected instead, the sister Angelman Syndrome is the result.

The most frequent disorder caused by known multiple gene overexpression is Down Syndrome.  We saw in earlier post that DS is caused by the presence of all or part of a third copy of chromosome 21.  This results in over-expression of some 300 genes.

Why So Many Syndromes

Even before the days of genetic testing, these syndromes had been identified.  How could that be?  Each syndrome is marked by clear physical differences.

These physical differences where used to identify those affected.

Within autism too, sometimes there are physical differences.  Big heads, small heads, slim stature or heavy stature, advanced bone age or retarded bone age.

So many syndromes , but no therapies

Many of the rare syndromes have their own foundations funding research, mainly on the basis that if there is a known genetic dysfunction there should be matching therapy somewhere.

As of today, there are no approved therapies for any of these syndromes.

The Futility of Genetic Research?

A great deal of autism research funding goes into looking for target genes.  The idea goes that once you know which gene is the problem you can work out how to correct it.  There are numerous scientific journal dedicated to this approach.

Since no progress has been made in treating known genetic conditions leading to “autism”, is all this research effort well directed?  Some clever researchers think it is not.

All I can do is make my observations from the side lines.

What do Down Syndrome, Autism and Pitt Hopkins Syndrome all have in common?

In at least some of those affected, they have the identical excitatory-inhibitory imbalance of GABA, that can be corrected by Bumetanide.

If you did whole exome genetic testing on the responders with these three conditions you would not find a common genetic dysfunction; and yet they respond to the same therapy.

I am actually all for continued genetic research, but those involved have got to understand its limitations, as well as its potential.

More on GABA

This post returns to the theme of the dysfunctional GABA neurotransmitter because the research indicates it is present in numerous of the above-mentioned conditions. 

Table 1.  Summary of GABAA signaling alterations in neurodevelopmental disorders (click for the full Table)

·        Autism

·        Fragile X

·        Rett Syndrome

·        Down Syndrome

·        Neurofibromatosis type 1

·        Tourette syndrome

·        Schizophrenia

·        Tuberous sclerosis complex (TSC)

·        Prader-Willi syndrome

·        Angelman Syndrome

Based on feedback to me, we should add Pitt Hopkins Syndrome to the above list.

The GABA dysfunction is not the same in all the above conditions, but at least in some people, Bumetanide is effective in cases of autism, Down Syndrome and Pitt Hopkins Syndrome.  I suspect that since it works in mice with Fragile-X , it will work in at least some humans.

GABA_A has already been covered in some depth in this blog, but I am always on the lookout for more on this subject, since interventions are highly effective.  It is complicated, but for those of you using Bumetanide, Low Dose Clonazepam, Oxytocin and some even Diamox, the paper below will be of interest.

Modulation of GABAergic transmission indevelopment and neurodevelopmental disorders: investigating physiology andpathology to gain therapeutic perspectives

Regular readers will know that in autism high levels of chloride Cl⁻ inside the neuron have been shown to make GABA excitatory rather than inhibitory.  This leads to neurons firing too frequently;  this results in effects ranging from anxiety to seizures and with reduced cognitive functioning.  Therapies revolve around reducing chloride levels, this can be done by restricting the flow in ,or by increasing the flow out.  The Na⁺/K⁺/Cl⁻ cotransporter NKCC1  imports Cl⁻ into the neuron.  By blocking this transporter using Bumetanide you can achieve lower Cl⁻ within the neuron, but with this drug you also affect NKCC2, an isoform present in the kidney, which is why Bumetanide is a diuretic.  Some experimental drugs are being tested that block NKCC1 without affecting NKCC2 and better cross the blood brain barrier. 

The interesting new approach is to restore Cl⁻ balance by increasing KCC2 expression at the plasma membrane.  This means increasing the number of transporters that carry  Cl⁻  out of the neurons.

Chloride extrusion enhancers as novel therapeutics for neurological diseases

In the Modulation of GABAergic transmission paper there is no mention of acetazolamide (Diamox) which I suggested in my posts could also reduce Cl⁻, but via the AE3 exchanger.  This would explain why Diamox can reduce seizures in some people.

The paper does mention oxytocin and it does occur to me that babies born via Cesarean/Caesarean section will completely miss this surge of the oxytocin hormone.  This oxytocin surge is suggested to be key to the GABA switch, which should occur soon after birth when GABA switches from excitatory to inhibitory.  In much autism this switch never takes place.

That would suggest that perhaps all babies born via Caesarean section should perhaps receive an artificial dose of oxytocin at birth.  This might then reduce the incidence of GABA dysfunctions in later life, which would include autism and some epilepsy.

Indeed, children born by Caesarean section (CS) are 20% more likely to develop autism.

Association Between Obstetric Mode of Delivery and Autism Spectrum Disorder - :  A Population-Based Sibling Design Study

Conclusions and Relevance  This study confirms previous findings that children born by CS are approximately 20% more likely to be diagnosed as having ASD. However, the association did not persist when using sibling controls, implying that this association is due to familial confounding by genetic and/or environmental factors.

So as not to repeat the vaccine/autism scare, the researchers do not say that Caesarean section leads to more autism, rather that the kinds of people who are born by Caesarean section already had an elevated risk of autism.  This is based on analysing sibling pairs, but I do not entirely buy into that argument.  They do not want to scare people from having a procedure that can be life-saving for mother and baby.

If you look at it rationally, you can see that the oxytocin surge at birth is there for an evolutionary reason.  It is very easy to recreate it with synthetic oxytocin.

Another interesting point is in the conflict of interest statement:-

Laura Cancedda is on the Provisional Application: US 61/919,195, 2013. Modulators of Intracellular Chloride Concentration For Treating An Intellectual Disability

Regular readers will note that in this blog we have known for some time that modifying GABA_A leads to improved cognitive function.  I even suggested to Ben-Ari that IQ should be measured in their autism trials for Bumetanide.  IQ is much less subjective than measures of autism.

Conclusion

My conclusion is that while genetic testing has its place, it is more productive to look at identifying and treating the downstream dysfunctions that are shared by many individual genetic dysfunctions.

By focusing on individual genes there is a big risk of just giving up, so if you have Pitt Hopkins Syndrome, like Peter the Wild Boy, it is a single gene cause of “autism” and there is no known therapy.  Well it seems that it shares downstream consequences with many other types of autism, so it is treatable after all.

I also think more people need to consider that cognitive dysfunction (Intellectual Disability/MR) may indeed be treatable, and not just via GABA; so good luck to Laura Cancedda.