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 RXLIST.com 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.

Why inflammation leads to a leaky blood-brain barrier: MicroRNA-155

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.

Conclusion

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.