Wednesday 21 September 2022

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 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:

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:

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)


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.



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.


Sunday 11 September 2022

Teletubbies is banned in our house, Peppa might get banned in Italy


Peter Griffin, from Family Guy, drawn by Monty

Today’s post is about cartoons rather than science.  Nowadays, cartoons play a big role in the childhood of many kids.  Kids with severe autism grow up to be adult-sized kids with autism and their love of cartoons never fades.

Cartoon characters feel like real characters to kids, perhaps more so than actors.

A polite way to judge severity of autism might be to just ask what kind of cartoons are watched.

We have a particularly broad range of cartoons because when Monty’s big brother was born, I wanted him to see some of the really great ones, that were not shown on TV where we live.  So we accumulated a vast array of videocassettes and then DVDs.

I was never a fan of baby TV and we rather skipped that genre and moved straight to the classics like Thomas the Tank Engine and many similar series, that seem to have been forgotten.

Monty has his iPad and his favourite spot at home is in a room facing the garden where he has his piano, and a TV with a DVD player and just about functional VCR.  His number one position is sitting on a bouncy (pilates) ball beside a large window while balancing his iPad on his knee.  To watch cartoons on the TV he just has to turn left slightly.

Monty was never a big Teletubby fan, but big brother must have seen him watching it, or checked the browsing history.  Teletubbies was banned. 

Like many people with autism, Monty really likes rules.  I don’t think he cares about Teletubbies at all, but he loves having a rule banning them.

 “Can you watch Teletubbies in B.P. street number 53?  Yes, or No?”

The correct answer is No, because no babies live there.

Cartoons have become categorized into suitable for babies, small boys, medium boys and big boys.

The Minions, long a big favourite of Monty’s, is fortunately suitable for everyone.  I am surprised that so many adults like it, not just Uncle Stuart.  I recently took Monty to see the newly released Minion movie and he was the youngest person in the audience and I was not the oldest.

I always liked stop-motion video.  This is the old-fashioned way of making cartoons when you use drawings or models and film them moving frame by frame.  When Monty’s big brother was 11 years old, he made this cartoon with his classmate.



The big hits in our house include:

The original Thomas the Tank Engine (before they used CGI), along with the books by the Reverend Wilbert Awdry   

Percy the Park Keeper, Bob the Builder, Brambly Hedge

Thunderbirds, Stingray and Captain Scarlet (made by filming models and puppets)

Wallace and Gromit (stop motion video with using plasticine figures), they won 3 Oscars

All the original Tom & Jerry

All the old Mickey Mouse, Bugs Bunny, Goofy going back to the 1930s

The earlier seasons of the Simpsons, when it was very good

Family Guy (see the above drawing of Peter Griffin - we also have a Lois and Chris)

South Park is more for me and big brother, who like what may appear to be politically incorrect, but actually is very inclusive.

We were never really into Peppa Pig, but Peppa is getting into trouble in Italy.

 Italian politician demands ban on Peppa Pig episode showing lesbian couple

A senior member of a far-right Italian political party tipped to win general elections this month has appealed to state broadcaster Rai not to screen an episode of the globally popular children’s cartoon series Peppa Pig over the inclusion of a same-sex couple in its cast of characters.


The episode, called Families, was shown for the first time in the UK on Tuesday, and features two co-parenting lesbian polar bears. A character called Penny announces: “I live with my mummy and my other mummy. One mummy is a doctor and one mummy cooks spaghetti.” The family then sit down for a meal together.

A much better example is Sanna Marin, the 36 year old Prime Minister of Finland; she has two mothers. Some people in Finland were shocked recently when she (and her male spouse) had a party at the official residence, photos leaked out and, horror of horrors, she really knows how to dance.  I would say that it a good thing - a Prime Minister whose dancing is not embarrassing! 

This then brings me to the latest work of autism self-advocates, Bruno the Brake Car.


            Bruno the Brake Car joins "Thomas & Friends" as first character with autism

 “Bruno rolls in reverse at the end of the train, which gives him a unique perspective on the world.  Detail-oriented Bruno enjoys schedules, routine, and knows where all the tracks lead on Sodor.  The engine car also uses his lantern on his red exterior to communicate his emotional state, moving when he is excited or cautious and he can create ear defenders by puffing out steam if he feels sensitive to loud noises.


This all sounds great, but out in the school yard don’t be surprised to have your child with mild autism be addressed by “Hey, Bruno!”, or “Your lights flashing again, Bruno!”.

I did do a quick check on political correctness and cartoons.

If you happen to watch Family Guy, you will know that Peter, the Dad, says many extremely unpleasant things to his daughter Meg (voice by Mila Kunis).  Some brothers now taunt their sisters by calling them Meg.  Mila Kunis, being interviewed by Graham Norton, told how she constantly gets told "Shut up Meg!"

On the other hand, in South Park we have two characters with cerebral palsy, Jimmy who walks with crutches but has normal IQ and Timmy, who is in a wheelchair, has a very low IQ and very limited speech.

While some people think South Park is a foulmouthed show (and it is), creators Trey Parker and Matt Stone really seem to 'get' disability much more so than many slightly disabled people, who self-advocate to the world.

The whole point is that Jimmy and Timmy are out there all day with the boys, behaving badly, getting into trouble and getting no special treatment.  That is real inclusion.

Who wants to be the brake car, at the back of train? Every boy, autistic or not, would want to be the engine, at the front, pulling the train.

Rather than asking the the Autistic Self Advocacy Network for advice, the producers of the new Thomas show should have asked Trey and Matt for advice.  The result would have been something I would watch.

Friday 2 September 2022

Bravo Monty! Academic results in Autism


Some risks are worth taking, however long the journey

Academic results are part of most people’s life, whether you love them or loathe them.

Most children diagnosed today with autism will do just fine at school, but this was not always the case.  Those born 20 or 30 years ago and diagnosed in early childhood with autism are usually in a much less fortunate position.

Today’s post is about level 3 autism and what the Lancet Commission want to call Profound autism. The new idea is that if by age of 8, a child with autism still has severe intellectual disability or minimal language then he/she can be best described as having Profound Autism.

In other literature the term SDA (Strictly Defined Autism) was proposed.  It means what was called autism back in the 1990s and earlier.

You can have severe autism with any level of IQ, which I think many people may not be aware of, or even accept.


Monty and his Academic Results

The “bravo” for Monty comes from Dr Ben-Ari, the scientific brain behind the idea to use Bumetanide to treat autism.

I wrote to tell him that after almost a decade of bumetanide, Monty has passed his externally graded high school exams.  In the English system they are called General Certificates of Secondary Education (GCSE), Monty took the international version called IGCSE. You normally take them at the age of 16, but we held Monty back 2 years at the age of 9 so he took them at 18 years old.

These exams are not graded by the school, they are sent away to be marked by someone who just sees your candidate number.  Of course it is still possible to fiddle the results, but this is not common.

Up to the age of 9, it was pretty clear that Monty would not even be attempting these exams.  It was assumed he would not be going to the high school.  His school has no resources for those with special needs.

Fast forward a decade and Monty made his way into high school and in 2022 sat his IGCSE exams.  His results included a B in science, a C in maths a C in English.  As I told Dr Ben Ari, Monty’s results will not take him to the Ivy League or a Grande École, over where he is in France.  For someone with Strictly Defined Autism (SDA) it is pretty remarkable.  

In the US you might well "graduate" high school, but the quotation marks hide the real picture. Graduation from special education just means you aged out of it.  Life is better without the quotation marks.

Bumetanide may have failed its phase 3 clinical trial, but for some people with severe autism it is a game changer.


Game Changer

My new book is also called Game Changer and it is currently being edited.

It will be available via Amazon as either an eBook or as a paperback.

The book is the length of a novel, about 90,000 words or 300 pages.  It is not intended for everyone to read from cover to cover.  It has plenty of non-scientific content and there is plenty in it a typical parent would find useful.


Facebook links

Facebook links to EpiphanyASD are no longer blocked.

Just use, not the old


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I could never use an iPad to do anything clever on the blog, just read it.