Ivermectin for Parasites, but as a PAK1 Inhibitor for Autism, Cancer and Leukemia?

In recent posts I introduced a substance called PAK1.  This substance is implicated in the mechanism behind many cancers and research at MIT showed that is also involved in autism, fragile X and schizophrenia.

PAK inhibitors notjust for Cancer, Alzheimer’s and Neurofibromatosis, but also for Autism, Schizophrenia, Fragile X and Shank 3

 

In that post, I pointed out that a great deal of research is being done to create new drugs that act as PAK inhibitors, none of which are yet approved.

But I also highlighted that Neurofibramatosis sufferers have been using a naturally occurring PAK inhibitor, called CAPE, that can be found in certain types of bee propolis.

The researchers ended up choosing a New Zealand variety called BIO 30, but they also pointed out that certain Brazilian, and even one Chinese propolis, are known PAK inhibitors.  The problem with all natural “supplements” is the lack of consistency; it turns out that the PAK inhibiting power of BIO 30 varies from year to year and batch to batch.

It was interesting that an old generic drug called Ivermectin is also a known inhibitor of PAK.  Ivermectin is a very basic drug, used all round the world to kill parasites in the intestines.  Many people’s pet dogs are given the veterinary version year round, and life-long.  It is a very well-known substance.

So I thought I would Google “Ivermectin and autism”, not expecting to find anything interesting, but I did, and hence the origins of this latest post.

Autism and Parasites  

It turns out that many autistic kids in the US have been given the anti-parasitic drug, Ivermectin, by “alternative practitioners” who think autism is caused by parasites.  Yes, caused by parasites.

Previously in this blog we heard about an intriguing treatment for autism that involves intentionally swallowing TSO parasites (Helminthic therapy).

I think that TSO is very interesting.  It is now being developed by Coronado Biosciences as a therapy for several inflammatory conditions including:-

·        Crohn’s disease

·        Ulcerative Colitis

·        Autism

Here is a link to all the clinical trials they are running.

The idea behind TSO is that the parasites have evolved a method of ensuring their survival in their host, by subduing the immune system, so that they are not killed/ejected.  By down-regulating the immune system, they become a therapy for diseasing featuring an over active immune system.

This all started a few years ago when one autism Dad figured all this out and tried it on his own son.  Then began the long process of clinical trials, which then ended up with Coronado Biosciences.  The Dad’s website is here.

In the world of “alternative doctors” they are giving Ivermectin and Praziquantel for autism, in the belief that the problem is worms.  A Dr Yu, in particular, who even has a presentation for Autism One, believes de-worming helps autism.

In the real world, Ivermectin is both a de-wormer and a PAK inhibitor.

Dr Yu has, inadvertently, been giving a PAK inhibitor to kids with autism.  He seems very happy with result.  I take note of his success.

PAK1, Autism and Cancer

PAK1 is required for the growth of 70% of human cancers, including prostate, colon, and breast and also for neurofibromatosis.  Since PAK1 is also now known to be implicated in autism, you may be wondering if people with autism are more prone to cancer.

Well the good news is the first study I found said apparently not; but on digging a bit deeper the story is less clear

The Correlation between Rates of Cancer and Autism: An Exploratory Ecological Investigation

High correlations were found between autism rates and the incidence of in situ breast cancer (p≤10⁻¹⁰, modified inverse chi square, n = 16) using data from states that adhere strictly to the Code of Federal Regulations for diagnosing autism. By contrast, few significant correlations were observed between autism prevalence and the incidence of 23 other female and 22 male cancers.

Conclusions

These findings suggest that there may be an association between autism and specific forms of cancer.

 

Autism and cancer risk

Abstract

A literature review was conducted on the genetic and developmental bases of autism in relation to genes and pathways associated with cancer risk. Convergent lines of evidence from four types of analysis: (1) recent theoretical studies on the causes of autism, (2) epidemiological studies, (3) genetic analyses linking autism with mutations in tumor suppressor genes and other cancer-associated genes and pathways, and (4) contrasts with schizophrenia, Parkinson's, and Alzheimer's disease indicate that autism may involve altered cancer risk. This evidence should motivate further epidemiological studies, and it provides useful insights into the nature of the genetic, epigenetic, and environmental factors underlying the etiologies of autism, other neurological conditions, and carcinogenesis.

Given how poor quality the data on autism incidence is, and that most people get cancer in old age, we should be very careful.  In a recent post we learned that many people in older age have autism, but were never diagnosed as such.  So it is likely that the true incidence of autism in cancer patients, is much higher than the data suggests.

It would seem highly plausible that autism might indeed predispose you to elevated cancer risk, so there is another good reason to look at PAK1 inhibitors.

Ivermectin and Leukemia

Leukemia /leukaemia is a cancer of the blood or bone marrow.

While this is a blog about autism, from time to time I do notice some very obvious signs towards therapies for other dysfunctions.  Both NAC and quercetin were shown to be beneficial in treating existing cancers; quercetin helped esophageal cancer and NAC was shown to helped breast cancer.

So when I checked to see if any cancer research had followed up on the cheap drug Ivermectin, I was pleased to see that somebody had thought of this already.   They had tested the effect of Ivermectin on leukemia cells, although they did not make the PAK1 connection.

The antiparasitic agent ivermectin induces chloride-dependent membranehyperpolarization and cell death in leukemia cells

 Ivermectin increased intracellular chloride ion concentrations and cell size in leukemia cells. Chloride influx was accompanied by plasma membrane hyperpolarization, but did not change mitochondrial membrane potential. Ivermectin also increased reactive oxygen species generation that was functionally important for ivermectin-induced cell death. Finally, ivermectin synergized with cytarabine and daunorubicin that also increase reactive oxygen species production. Thus, given its known toxicology and pharmacology, ivermectin could be rapidly advanced into clinical trial for leukemia.

   

Since Ivermectin is off-patent there is no financial interest for the private sector to research its use in clinical trials.  Perhaps Ivermectin should join NAC and quercetin on my list of cheap cancer drugs.

Conclusion

The conclusion is that Ivermectin may very well be an effective autism treatment, perhaps we should ask Dr Yu for some data?

The reason the Japanese researchers propose Propolis ahead of Ivermectin to treat Neurofibromatosis seems to be that in 99% of people there are no side effects, even at huge doses.  Ivermectin does react with many drugs.  Ivermectin does not normally cross the blood brain barrier (BBB); the effect of other drugs is to increase the flow across the BBB.

Clearly autism is a disease of the brain, but I presume inhibiting PAK outside the brain will reduce the concentration of PAK within the brain.  Does the CAPE in propolis cross the BBB?  Does it need to?

It may be that taking Ivermectin, with the contra-indicated drugs, but in a low dosage is in fact the optimal therapy, since it will then better cross the BBB.

I will start with a dose of New Zealand propolis and see if it has any effect; hopefully it comes from a good year.

If any readers have tried Ivermectin for autism, based on Dr Yu, Dr Klinghardt or anyone else’s “protocol”, I would love to hear from you.

P.S.

The really thorough review of possible PAK1 inhibitors, that I highlighted in the early post, is this one:-

Effective neurofibromatosis therapeutics blocking the oncogenic kinase PAK1