Friday, 6 June 2014

PAK1 Therapy for Autism – All packed and ready to go!

Following up on recent posts about PAK1, whose presence is required for 70% of cancers to grow and MIT have implicated in several types of autism, I have collected all the data I can find to make trials of PAK1 inhibition in autism.
I contacted the leading Japanese researcher who has developed PAK1 therapies for various kinds of tumor, mainly found in neurofibromatosis, but also brain tumors and even epilepsy.  He suggested the dosage of the CAPE-rich propolis from New Zealand and also suggested another drug called Fingolimod/Gilenya.  

This drug is an immunomodulating drug, approved for treating multiple sclerosis, but it is also a PAK1 inhibitor.  It appears to cross the blood brain barrier.  The downside it that Gilenya is hugely expensive, costing around $50,000 a year.
While Tonegawa's group at MIT continue to develop their new PAK1 inhibitors, I am concerned that they will end up with a drug costing as much as Gilenya, which will put it out of reach of most people, even if it was effective.

So that brings me back to the trials I propose.

Trial 1   -  BIO 30 Propolis

This is a natural product and as such will appeal to many of this blogs readers.  It needs no prescription from your doctor.  You can buy it over the internet from numerous pharmacies in New Zealand.

The dosage proposed for autism by the Japanese Researcher is 1-2 ml per 10 kg of body weight.

It appears that about 1% of people have an allergy to bee products.  If you are in the 99%, it is reported that even very much larger doses of BIO 30 have no side effects.

Trial 2   -  Ivermectin/Stromectol

This is the cheap drug that is used to treat parasites, but turns out to be a PAK1 inhibitor.  It was also recently shown to kill leukemia cells.

Here I will draw on the autism worm-dosage used by Dr Wu, who prescribes Ivermectin in the belief that the autistic kids’ behaviours are driven by worms.

Dr Yu is combining Ivermectin with other anti-parasite drugs.  I am assuming he “got it right for the wrong reason”, in other words the worms are not the issue, PAK1 is the issue.

Below is the dosage Dr Yu suggests in his autism presentation and one case report where there was a before and after evaluation.  Here the ATEC was used, which is a scale designed by Bernard Rimland and Stephen M.Edelson of the Autism Research Institute (the DAN people).


From what I could find, a single dose of Ivermectin (Stromectol) should kill the parasites.  Pets are given the same drug on a regular basis, some preventatively.

In low doses it appears to be very safe, but not in high doses.

Strongyloidiasis is a human parasitic disease caused by the nematode (roundworm).  On the site the dosage for Strongyloidiasis is:-

The above is for a single dose therapy.  Dr Wu’s worms are either much more resilient, or his much higher and multiple dose therapy is actually working for entirely different reasons.

Trial 3   -   Fingolimod/Gilenya

Given the huge cost of Gilenya, I cannot imagine anybody trying it for autism.  Perhaps Novartis would like to donate some?

We did cover immunomodulatory therapy in earlier posts and it was Dr Chez who likes to write about this subject, in relation to autism.  He has published several trials and a good book.

Perhaps he should do the Gilenya trial?

The Blood Brain Barrier

I did ask the Japanese researcher if CAPE, the anti-PAK1 ingredient of the New Zealand propolis can cross the blood brain barrier, since it is claimed that Ivermectin does not.  He says that BIO30 and Fingolimod/Gilenya cross the BBB.

This brings me to a slight diversion.

In this research the aim was to confirm the mechanism behind why inflammation causes the blood brain barrier (BBB) to leak.  It has been suggested that the leaky BBB is a key part of autism.  The less leaky it is the better for autism.  Since pro-inflammatory agents like histamine and IL-6 really do make autism worse, it is highly relevant that the research shows that pro-inflammatory agents cause the BBB to let through more of the substances that it is supposed to keep out.

Perhaps the ever-present pro-inflammatory cytokines found in autism, mean that the BBB is always partially compromised.  A drug like Ivermectin might therefore pass more freely across the BBB, than would be expected in other people.

So Ivermectin might remain a cheap alternative to Gilenya.  Dr Yu’s case studies perhaps warrant some more serious attention.

Will it work?

There are good reasons why PAK1 inhibition should have a positive effect.  It is definitely not quack science, it is the serious MIT kind.

In treating Neurofibromatosis NF-1 tumors, it does seem to be more effective at stopping new tumors, rather than shrinking existing ones.   This perhaps should not be surprising, since PAK1 is needed for a tumor to grow and may not be needed for it to live.  At much higher doses, it is reported that existing tumors shrink. So with autism, maybe PAK1 is needed early on, before birth; blocking PAK1 in a 10 year old may be pointless.

The only way to find out for sure if it works in your type of autism is to try it.

If it does not work for Monty, aged 10 with ASD, we cannot say it will not work in somebody’s two year old with a different type of autism.

Also, in Monty, the PAK1 effect might already be being mitigated by his existing drugs.

It would be helpful if there was a clinical trial, but there is not.


Trial 1 is easy to do at home, and if you do it for a month, you would need two bottles of propolis, costing $50 including shipping from New Zealand.

Since the Nobel Laureate from MIT tells us that autism requires PAK1 and that, in mouse models of autism, PAK1 inhibitors are effective treatments, it seems odd nobody has tried it.  In PAK1-driven Neurofibromatosis, there are now many people claiming BIO30 to be effective.  In this condition you can measure/count the tumors, so I guess they should know if it works.

The MIT-inspired drugs, like Tonegawa’s FRAX486 will not be available for many years, and who knows how much they will cost.

In the case of Ivermectin, somebody really should look at the toxicology data and see how safe regular usage would be in humans.  The Leukemia researchers proposed this drug be actively developed, but nothing seems to have happened.  Just for a few days, Trial 2 would not seem to be too risky.

We agree to leave trial 3 to Dr Chez, in Sacramento.


  1. I'm a parent of a 4 year old diagnosed with ASD (regressive form). I've recently recently discovered your blog, and wanted to tell you how much I appreciate your insight. I am also glad to see a parent like myself searching for a true understanding, and hopefully a cure/treatment that works.
    In one of your next posts, you write that you believe that many/most cases of regressive autism is in actuality caused by an infection as is the case with Pandas/Pans. I'm just trying to understand how you reconcile that with Pak 1 inhibition. If it's the infection that's ultimately causing the neuro-inflammation, then it would seem that you would need life-long therapy since you are only treating the symptom. Is it possible that Dr Wyu is right in the sense that you need to kill the underlying infection (parasite?) which would make the case for Invermectin over the bio30?

    1. Nobody can say much for sure regarding autism. I suspect PAK1 will only be relevant for certain types of autism, nobody has gone beyond mouse models. Most of the mouse models seem to be relevant more to Classic Autism.

      I think PANDAS/PANS is a completely different disorder, that just happens to have some symptoms similar to autism.

      I think there are likely several different disorders that lead to regressive autism. One parent has tried all "my" drugs on his son with regressive autism and none had any effect. In the Bumetanide clinical trial some people with regressive autism were improved. Unless you live in an area of poor hygiene, parasites would seem highly unlikely to be the problem.

      The problem of long term Invermectin use would be its toxicity, short term should not be a problem.

      The only way to make progress is to do your own "clinical trials" at home. Most people cannot get access to the drugs and so give up.

      Many of the drugs are actually quite easy to get hold of either over the internet or via visiting a country that is not fussy about prescriptions.

      My experiments all relate to classic autism, they may or may not be helpful in other types of autism. The best drugs are in my PolyPiIl, and in my son produce a dramatic improvement. I would try each one individually and see what works.

  2. Peter, Have you done your Bio30 trial yet?

    I am thinking of trying it out very soon.

    1. I have just started experimenting with how to give it. It has a very strong taste and it does not dissolve in water, it just forms caramel-like blobs. It sticks to plastic. It would be easy to waste 50% of the dose. The best idea so far is to put the drops of propolis on a small piece of toast and put Nutella on top. This does work and I get 30 drops in two mouthfuls. The dose suggested by the Japanese researcher is even more than this.

  3. I assume you are trying the liquid. Have you considered the tablets? Since my son is G-Tube fed, administering liquid medication is very easy and precise for us, so I will be buying the liquid and trying that soon.

    Thanks again for your work. You location of those Australian sprouts has made a big impact on our lives! I am very eager to find out if any of these other innovations will work also.

    When you go to bed tonight, please know that you have made a positive impact on another ASD family 1000's of miles away from you.

  4. I don't know what your G-tube is made of, I suppose it is plastic. When I measured propolis in a 2.5 ml plastic spoon, it stained the spoon. Even after being in the dishwasher it did not come clean, I had to scrape it off. So I would suggest mixing it in something to avoid this problem. Perhaps crushing tablets might even be better. I am sure if you buy some US liquid propolis you can experiment on how to give it. If it messes up the G-Tube, it will cause other problems.

    Maybe propolis mixed in some dense "fluid" it will stay in suspension. In fact the liquid used by compounding pharmacies to make a "syrup" out of crushed pills, might work. Some body else suggested ice cream.

    My son will not swallow tablets and the dose is very high so a lot of tablets would be needed.

    I am very happy that your son is improving. I suggest you tell your doctor and other parents, since this seems to be the only way to spread the word. I found out recently that some parents were using NAC ten years ago, and yet 99.99% of serious doctors will tell you that autism is untreatable. You will see in the next post on Biotin, that in a small percentage of cases "autism" is indeed very treatable; the answer is there in the literature and nobody acts.

  5. Peter, how is the Propolis trial going?

    1. I am using about 2ml per day, which is less than the 3-6ml suggested by the Japanese researcher.

      I cannot be 100% sure of the propolis effect, since I continue to use the broccoli powder, which is itself quite recent. It seems to me that there is now even more speech and indeed my wife thinks there is too much. Some definitely is verbal stereotypy, but much is not. He is just saying everything that is coming into his head and commenting on anything he sees.

      The broccoli did increase speech, but it also produced euphoria, which was unmistakable. I think the mood change is the best proof of its effect.

      I was hoping to see a cognitive effect from the Propolis, if it really is a PAK1 inhibitor. Memory could also be affected, but that has never been a problem. Signs of cognitive improvement for my son would come from speech, academic work like math, or piano playing.

      I think something is changing, so I will continue. But is could also be due to the broccoli.

      I am not bothered about repetitive speech or even him talking to himself under his breath. This is a vast step forward from being non-verbal and then “restricted verbal”. I think any "excess" speech can later be redirected to something else.

  6. Hi Peter,

    Are you still trying Bio30? Any conclusions yet?

    1. Over Christmas and New Year we were away from home and I decided to keep things simple and stop the Bio30.

      I will restart it.

      The conclusions so far are that there are no side effects, at the low starting dose there is no "shock" improvement, but it is possible that there was a gradual cognitive improvement. I remain open-minded.


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