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.
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.