I should start this post by highlighting that generally cancer and autism are not caused by parasites.
I
have to be a little careful because we now know that certain types of virus and
bacteria are involved in the initial trigger to initiate some types of cancer.
This is why many females are now offered human
papillomavirus (HPV) vaccines to minimize the chance of several different
cancers. I noticed recently that in the US this vaccine is advertised on TV. I used to know a woman who like most people had the HPV virus as a child, but did not have this vaccine. She developed a rare oral cancer that the vaccine would have protected against and died very young. We saw in a previous post how a specific gut bacteria blocks the
initiation of childhood leukemia.
The pharmaceutical industry does not seem to like the idea of
repurposing existing drugs to treat a different disease. There are some exceptions; it is OK to treat
females with acne, using the diuretic drug Spironolactone. Nobody seems to object to the treatment of
intractable headaches with drugs actually approved to lower blood pressure (Verapamil,
Amlodipine etc).
When investigating cancers you have to look at the specific
underlying mechanisms, just as you do with autism.
As we saw long ago in this blog, it has been suggested to
classify autism as either over-active pro-growth signaling pathways, or under-active
pro-growth signaling pathways. Most is the over-active type.
Cancer is very clearly another example of over-active
pro-growth signaling pathways, so it is not surprising that there is an overlap
between therapies for autism and cancer.
The difference is that they are far more likely to be effective in
autism.
So, a cheap anti-parasite drug for kids like Mebendazole, which just happens to also be a Wnt inhibitor, may slow down the growth of some cancers, but it is sadly not curative. In an autistic brain where Wnt signalling might be overactive, a lower dose of Mebendazole, might well provide a long-term benefit.
My old posts that mention Wnt signaling are here:-
https://www.epiphanyasd.com/search/label/Wnt
Wnt signaling interestingly plays a role in how your hair
will go gray/grey. If you reduce Wnt signaling, your hair will go gray and so
this is an inevitable side effect of a potent Wnt inhibitor.
Premature graying might indeed indicate reduced Wnt activity.
Pyrantel pamoate
Our reader Dragos recently fined tuned his adult son’s anti-aggression
therapy and he recently shared his latest innovation:-
"you
have to give him 20mg of propranolol 2-3 times a day, pyrantel pamoate 750mg in
the evening for 2-3 days, and you will see that his anger will disappear, stay
on propranolol. After 3 weeks repeat with antiparasitic, you will see that I
was right, you don't use psychotropic drugs"
Propranolol is a normally used to lower blood pressure, but
it does this in a way that also reduces anxiety. At the low doses used by Dragos, it has been
used to treat actors with stage fright. It can be used before exams or driving
tests, to calm the person down.
Propranolol has been trialed in autism. Some people use a low
dose and some use a higher dose.
Pyrantel pamoate is used to treat hookworms and other
parasites that can be picked up by young children. It works by paralyzing the
worms. This is achieved by blocking certain acetylcholine receptors in the worm.
As is
very often the case, pyrantel pamoate likely has other modes
of action that are entirely different. Is it a Wnt inhibitor like the other
hookworm treatment Mebendazole?
I did a quick search on google and it gave me the wrong pamoate.
Pyrvinium pamoate is able to kill various cancer cells, especially CSC. The drug functions through the reduction of WNT- and Hedgehog-dependent signaling pathways (Dattilo et al., 2020).
Pyrvinium
pamoate is yet another anti-parasitic drug, but not the one Dragos is using.
So pyrantel pamoate may not be a Wnt inhibitor, unlike many anthelmintic drugs, but it is used by the “anti-parasitic re-purposer in chief” Dr
Simon Wu. He publishes his
findings/thoughts, which is good to see.
He likes to combine different anti-parasitic drugs.
I did look up the effect of pyrantel pamoate on gene
expression. There is data, but you
really need to see the source material to know whether anything is valid.
Inhibiting GSTP1 (glutathione
S-transferase pi 1) is suggested and that is a feature in common with an
anti-parasite drug class called Thiazolides (e.g. Nitazoxanide). That would make pyrantel pamoate a potential
therapy for triple-negative breast cancer, where the cancer cells rely on
vigorous activity by the enzyme glutathione-S-transferase Pi1 (GSTP1). Cancer cells are highly vulnerable to
oxidative stress, and as we know glutathione is the main way the body
extinguishes it. Glutathione
S-transferases
P1 protects breast cancer cell from cell death. So you want to inhibit GSTP1.
Pyrantel has many other suggested
effects even reducing expression of the gene FXR2 (fragile X mental
retardation,2) and increasing expression of the gene MTSS1 (metastasis
suppressor 1).
Pyrantel is even suggested as an
epilepsy drug.
Drug repositioning in epilepsy reveals novel antiseizure candidates
Epilepsy treatment falls short in ~30% of cases. A better
understanding of epilepsy pathophysiology can guide rational drug development
in this difficult to treat condition. We tested a low-cost, drug-repositioning
strategy to identify candidate epilepsy drugs that are already FDA-approved and
might be immediately tested in epilepsy patients who require new therapies.
Expanding on these analyses of epilepsy gene expression
signatures, this study generated a list of 184 candidate anti-epilepsy
compounds. This list of possible seizure suppressing compounds includes 129
drugs that have been previously studied in some model of seizures and 55 that
have never been studied in the context of seizures. 91 of these 184 compounds
are already FDA approved for human use, but not for treating seizures or
epilepsy. We selected four
of these drugs (doxycycline, metformin, nifedipine, and pyrantel tartrate) to
test for seizure suppression in vivo.
Pyrantel tartrate is an antiparasitic agent that acts by
inhibiting fumarate reductase, and by directly acting on acetylcholine
receptors at the neuromuscular junction of infecting helminths. Pyrantel
tartrate is FDA approved for use in domestic animals and has been used to treat
human parasitic infections.73 Unlike nifedipine and metformin (for which some
rodent studies and human reports relate to seizures), a March 2018 PubMed
search for “pyrantel and epilepsy” and “pyrantel and seizure” found no
manuscripts that studied pyrantel in seizures. Thus, pyrantel tartrate represents a truly novel
antiseizure drug candidate yielded by our screen.
All in all it is not surprising that Dr
Yu is prescribing pyrantel pamoate.
Digging any deeper is beyond the scope
of a blog post.
What is clear is that pyrantel pamoate and mebendazole are
unlikely to be equally effective in Dragos’ son.
Other anti-parasite drugs work very differently.
In the chart the mode of action of some common drugs is presented.
Anthelminticsfor drug repurposing: Opportunities and challenges
Mode of action of albendazole (ABZ), ivermectin (IVM), levamisole (LV), mebendazole (MBZ), niclosamide (NIC), flubendazole (FLU), rafoxanide (RAF), nitazoxanide (NTZ), pyrvinium pamoate (PP), and eprinomectin (EP).
Suramin is now quite well known as a potential autism therapy
and two different groups are trying to commercialize it. Suramin is the original anti-purinergic
drug (APD), it blocks purinergic receptors that have names
like P2Y2.
When I looked at PAK1 a long time ago, which was put forward
as a treatment pathway for neurofibromatosis, some schizophrenia and some
autism I came across Ivermectin as an existing alternative to the research drug
FRAX486, or the expensive BIO 30 propolis from New Zealand.
A decade later and the world goes crazy when the idea of using Ivermectin to treat COVID 19 gets well publicized. The good news is that now we know that regular use of Ivermectin is not as dangerous as people thought it would be. Many people have been using the veterinary version in the US, Brazil and elsewhere.
The supporting research:-
Effect of Pyrantel on gene
expression.
decreases expression of:-
FXR2 fragile X mental retardation, autosomal
homolog 2
(and many more)
Increases expression of
MTSS1 metastasis suppressor
1
BNIP1 BCL2/adenovirus E1B
19kDa interacting protein 1
BRAF B-Raf proto-oncogene,
serine/threonine kinase
(and many more)
https://maayanlab.cloud/Harmonizome/gene_set/Pyrantel+Pamoate/CTD+Gene-Chemical+Interactions
Glutathione
S-transferase P is an enzyme that in humans is encoded by the GSTP1 gene.
Pyrantel Pamoate Gene Set
Dataset CTD
Gene-Chemical Interactions
2 genes/proteins interacting with the
chemical Pyrantel Pamoate from the curated CTD Gene-Chemical Interactions
dataset.
GPR35
G protein-coupled receptor 35
GSTP1
glutathione S-transferase pi 1
Triple-negative breast cancer target is found
They discovered that cells
from triple-negative breast cancer cells rely on vigorous activity by an enzyme
called glutathione-S-transferase Pi1 (GSTP1). They showed that in cancer cells,
GSTP1 regulates a type of metabolism called glycolysis, and that inhibition of
GSTP1 impairs glycolytic metabolism in triple-negative cancer cells, starving
them of energy, nutrients and signaling capability. Normal cells do not rely as
much on this particular metabolic pathway to obtain usable chemical energy, but
cells within many tumors heavily favor glycolysis.
"Inhibiting GSTP1 impairs glycolytic metabolism," Nomura said. "More broadly, this inhibition starves triple-negative breast cancer cells, preventing them from making the macromolecules they need, including the lipids they need to make membranes and the nucleic acids they need to make DNA. It also prevents these cells from making enough ATP, the molecule that is the basic energy fuel for cells."
Anthelmintics for drug repurposing: Opportunities and challenges
It has been demonstrated that some of the anthelmintics are able to inhibit critical oncogenic pathways, such as Wnt/β-catenin, signal transducer and activator of transcription proteins 3 (STAT3), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB; therefore, their application for cancer treatment has been considered.
Repositioning
of Anthelmintic Drugs for the Treatment of Cancers of the Digestive System
Anthelmintics
for drug repurposing: Opportunities and challenges
Mode of action of albendazole (ABZ), ivermectin (IVM), levamisole (LV), mebendazole (MBZ), niclosamide (NIC), flubendazole (FLU), rafoxanide (RAF), nitazoxanide (NTZ), pyrvinium pamoate (PP), and eprinomectin (EP).
Thiazolides inhibit
growth and induce glutathione-S-transferase Pi (GSTP1)-dependent cell death in
human colon cancer cells
More research on the repurposing anti-parasite drugs:
Chronic inflammation is a new catch phrase for the explanation of all chronic degenerative diseases, from asthma, arthritis, heart disease, auto-immune disease, and irritable bowel disease to cancer. Occult infections from oncovirus, bacterial, and fungal infections as well as from lesser known parasitic infections are driving forces in the cellular evolution and degeneration of cancer cells. An approach using currently available medications that target both fungal and parasitic metabolism appears to interfere with the metabolic synergy that is associated with tumor growth and aggressiveness
The Antitumor Potentials of Benzimidazole Anthelmintics as Repurposing Drugs
Repurposing Drugs in Oncology (ReDO)—mebendazole as an anti-cancer agent
A Pinworm Medication Is Being Tested As A Potential Anti-Cancer Drug
I did suggest long ago that Mebendazole, as a Wnt inhibitor, might be a cheap and effective treatment for some autism. I had envisaged that it would need to be given daily, as it is in the cancer trials.
Dragos’ use of pyrantel pamoate, for an average
of 4 days a month is interesting. It is cheap,
safe and practical.
One key issue with antiparasitic drugs is how much is
absorbed into the blood stream. If 100%
of the drug stays in the gut, its benefit will be limited.
About 20% of Mebendazole ends up in the blood stream and if
you take it often this figure is reported to increase.
The combo of propranolol + pyrantel pamoate is
an interesting option to treat self-injury and aggressive behavior. It works for Dragos and undoubtedly will for
some others.
Is the inhibition of Wnt signalling the reason why pyrantel
pamoate is effective for Dragos’ son? There
is no evidence to support that.
Are antiparasitic drugs going to be widely adopted to treat
any unrelated conditions, cancer included, I very much doubt it.
Cancer is better avoided, than treated. It is a much more achievable objective.
The Fragile X researcher Randi Hagerman takes metformin, as
her chemoprevention therapy. She is the medical director of MIND Institute at the University of California,
Davis.
You can raise IQ in people with Fragile X by 10-15% using Metformin. I guess Randi had been reading up on
Metformin and came across the anti-cancer effects.
If I had to suggest an anti-parasite drug for Randi to try in
Fragile X, I would suggest the PAK inhibitor Ivermectin, made (in)famous by
Donald Trump and Jair Bolsonaro during Covid. The research drug FRAX 486 is
called FRAX for Fragile X. It is a PAK inhibitor that never made it to market. Ivermectin is an existing drug that is also a
PAK inhibitor. Worth a try, Randi?
I expect Dr Yu might try and increases his chances and make a
combo with a second anti-parasitic drug.
Metformin is one of several anti-cancer choices, it depends
which type of cancer is of concern. For RAS-dependent cancer I think
Atorvastatin is the best choice.
If you read the research, like me and
Randi, chemoprevention
is the obvious choice for older adults. Dementia prevention is equally obvious.
Parkinson’s prevention may be achieved by blocking Cav1.3
(amlodipine etc)
Alzheimer’s prevention may be achieved using low dose fenamates
(Ponstan etc).
For vascular dementia and Alzheimer’s prevention/treatment
spermidine (in the form of modified wheatgerm) is promising.
Anti-parasite drugs for cancer and autism? Yes, it sounds
mad. But is it?
What is for sure is that your pediatrician will think you
have gone mad!
Our reader MG in Hong Kong will have got some new ideas to
think about.
Hello Peter,
ReplyDeleteHow do I know the type of autism(overactive or under active pro-growth signaling pathways) and how to treat. Does suramin, ivermectin and bio 30 propolis has similar affects?
My son is soon to be 8 and yet to speak(non verbal). He loses his words/skills often. We have tried Bumetanide for 3 months and didn’t see any change, we wanted to continue but his urine frequency throughout the day increased and the incontinence started so we stopped. Urine incontinence was caused due to fungal overgrowth as shown in his oats and mycotox reports. And when started treatment it has improved a lot, no more accidents from 20-25 a day.
We go in cycles and I feel we have stuck, looking for some help. Thanks
If your child was born large, perhaps with a big head, or unusually muscular that might indicate hyper-active pro-growth signaling. If your child was born small, perhaps with an unusually small head that might suggest the opposite which is hypo (under-active).
DeleteThis a just a way to segment autism into categories as a step towards identifying smaller sub-types.
Suramin is very different to Ivermectin. BIO 30 propolis is a mild PAK inhibitor, Ivermectin shares this effect, but is more potent.
If you have the resources, whole exome sequencing (WES) is one way to narrow down the type of autism.
There are very many treatment options, but you need to have some targets. For example anti-inflammatory, pro-myelination, anti-oxidative, growth factors etc. To know what to target you need to understand your child’s autism vs everyone else. Understanding any comorbidities, family history, issues during pregnancy/birth, physical differences, genetic testing results etc, helps you to understand what you are dealing with. The autism diagnosis itself is not very useful.
Hello, Peter, thank you very much for the article you posted, I hope that many of us who see us will understand that the diagnosis of "autism" is a false one. We have been fighting this disease for 16 years, which is actually an infection of a virus , which is mostly triggered by the MMR vaccine. Please try methylene blue as a treatment, we use 2-3 drops 3 times a day, and when the horse jumps, an antiparasitic plug (pamoate or nikvorm). We will soon start with apricot kernel extract and wild cherry bark extract, it seems that the lack of thiocyanate cannot activate the immune system to destroy viruses and bacteria, I will keep you informed.....
DeleteThanks for responding. My son was born small about 2.7kg, but now he is normal size for his age. We don’t have not done wes sequencing yet but in process to do. However we have ruled out fragilex and Rett syndrome. We have tried a lot of maps doctors and done biomed. I can’t figure out the issue on my own. I try very hard day/night but it’s so complex. When we think we have gotten hold of 1 thing the other issue starts and we go in circles. I have tried Thorne NAC 3 times a day for 3 months and saw nothing. He is usually very happy and cuddly, has good eye contact and receptive language.
DeleteBut his days are spent on repetitive play, no focus on any learning activities including device communication.
It’s so hard to what to do next.
In our case migration, stress during and after pregnancy and alpha female theory all could play a part. I and my husband both are software programmers and not very social. But my son is at severe end of spectrum with ID due to his speech/communication issues and my daughter is super intelligent(gifted) and very social.
DeleteTo both of the last 2 commenters make a one month trial of bumetanide. The odds suggest it likely will work for one of you.
DeleteLoss of words/skills and repetitive play sounds like both long and short-term memory is not working well. The reason could be anything, but I would start with a WES and an EEG. Having the rest of the family on the gifted side I think a genetic cause is very plausible. Good eye contact suggests inhibition works OK, while excitation could be low. Maybe check memory enhancement stuff?
Delete/Ling
Hello Ling, we have done 1hr eeg twice and mri. Everything came back normal. Doctor wouldn’t agree to do longer eeg. We have also requested for Wes but not sure if it will be done. I also saw your comment about wnt activator. We’re able to use it successfully?
DeleteYou can activate Wnt signaling with simvastatin/lovastatin/atorvastatin. This is suggested to be one of the reasons these drugs give a benefit in Alzeimer's. They have several other possibly beneficial effects as well.
DeleteNo, we haven't tried any of the Wnt activators Peter mentions above. Nor lithium, which also is an option for that purpose.
DeleteIt really sounds like a genetic test is the next step for you. There are genetic panels for ID, but if it is possible I would push for a WES and comparing parents' with child's DNA ("trio sequencing").
Not only would you possibly get an explanation to your child's condition, but maybe also learn if there are other health concerns to be aware of - and prevent.
Do you experience any other possible symptoms beyond ID and speech? Activity level? Sleep? Stimming? Dental issues? Hypotonia? Fine/gross motor skills? Immune system related stuff?
Etcetera - there can be lots of clues if you just look for them.
/Ling
Hello Peter and Ling, We have now done our WES(trio sequencing). They didn't find any gene for ASD, ID or epilepsy. They also didn't find anything for any other diseases.
DeleteMy son had very bad sleep issues but now it's manageable after years of biomed, he still takes melatonin to fall asleep. He also has lots of stemming/OCD.
Other than that everything is ok, he has gross motor similar to his age kids and fine motor too, but he is not interested in writing or drawing he won't do it. No dental issue.
I recently tried ivermectin for a week and his over stemming and inattentiveness improved.
We have already tried Bumetanide and NAC for 3 month and didn't see improvements.
Thanks
Did you have his tonsils/adenoids looked at? Sometimes ASD kids have undiagnosed sleep apnea which wakes them up at night.
Delete-Stephen
Investigating differences in symptomatology and age at diagnosis of obstructive sleep apnea in children with and without autism
Deletehttps://www.sciencedirect.com/science/article/abs/pii/S0165587622001525?via%3Dihub
Cardiometabolic risk profile in non-obese children with obstructive sleep apnea syndrome
Deletehttps://link.springer.com/article/10.1007/s00431-021-04366-8
"In fact, it could be supposed that gas exchange abnormalities and sleep disturbance characterizing OSAS promote inflammatory responses, as supported by the increased CRP levels observed in our cohort.
The association between SRDB and cardiovascular disease in pediatric age has been well documented, particularly in children with endothelial function impairment [44,45,46]. Moreover, these patients experienced recurrent episodes of hypoxiemia leading to an increase in sympathetic activity, oxidative stress, and inflammation (mainly expressed as elevated serum C-reactive protein levels) that enhanced endothelial dysfunction."
Hi Peter, My son was born with head circumference at 11th percentile and at 4 yrs he is at 14th percentile. Weight wise he stays under 6 percentile constantly from birth.Would he still fit the pro-growth signaling pathway? I know a child who is in his class, who has a notably very small head with ataxia. Surprisingly that child has a great eye contact.
ReplyDeleteRecently for Pitt Hopkins you recommended Mebandazole for wnt inhibition. But in your earlier presentation you recommended Lithium and statins to activate wnt signaling for Pitt Hopkins. Do you still think it's the wnt inhibition that would help in Pitt Hopkins? I'm planning to try Nicardipine soon nevertheless.
Janu, much is not well defined in human biology and often the actual effect can be the exact opposite of what you expected. For example when looking at P2X7 you could argue that either Oxatomide or Clemastine might be helpful, but they have the opposite function. IL6 is a proinflammatory cytokine, but it can also be the exact opposite.
DeleteWnt signaling is one of many possibly affected pathways. The super easy, cheap and safe first step would be to try the inhibitor. Then try the opposite.
Your son fits the hypo-active pro-growth signaling, which is the smaller part of autism. The idea comes from this Johns Hopkins paper.
DeleteCharacterizing autism spectrum disorders by key biochemical pathways
https://www.frontiersin.org/articles/10.3389/fnins.2015.00313/full
Hello Peter, we have had early hair graying in family and my son already has one gray hair. I suppose that would be hypo signaling. What’s best in case of hypo to try.
DeleteThanks
Mandy
Mandy early hair graying is a complex process that also involves a gene call BCl2. This interacts with Wnt signaling.
DeleteMy guess, and it is just my opinion is that hair graying might suggest the use of Atorvastatin, which is a common cholesterol lowering drug. I just looked it up in Google and came across a report of a person with blond hair who developed gray hairs, when they started taking this type of statin drug the gray hairs started to turn black. Clearly this is a rare case, it is not common.
My son has been taking Atorvastatin for several years, as have I.
Are your relatives with early graying short or tall? It would make most sense if they were short.
Thanks for responding. My father had early graying and he was average height. I too had early graying in my 20’s and I am bit taller than average. My son also has average height and weight for his age.
DeleteI have never tested his cholesterol level, I should now. I know it’s not required to start the medicine but it might give some indication.
Mandy
Janu, I would like to be connected , are you on FB or maybe in PTHS group?
DeleteAnonymous, drop me an email at januv@protonmail.com and we can connect from there.
Deletehttps://pubmed.ncbi.nlm.nih.gov/22430099/
DeleteParasite med il6
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114764/
DeleteIl6 autism brain
Hello Peter,
ReplyDeleteI just finished a book that I thought might interest some of your readers: Brain Energy by Christopher M. Palmer, M.D. It proposes that mental illness symptoms, including those of Autism, may be caused by energy imbalances in the brain caused ultimately by mitochondrial dysfunction. My son has areas of both underactivity and overactivity on a SPECT scan, and this book proposes that mitochondrial dysfunction causes both. I know that my son has a genetic polymorphism (gain of function) on TNF-a. However, I learned reading this book that TNF-a affects mitochondrial function. If any readers of your blog read the book, I would be interested in hearing their thoughts.
Thanks for the book tip. Mitochondrial dysfunction is suggested to be widespread in autism.
DeleteYou could try Humira, it is quite widely used by people with autism.
Mebendazole did nothing when used for the usual reason and in the usual dosing. I expected to see a bad reaction given it's a Wnt inhibitor, but had no other alternative than to use it at the occasion. (In my specific case I know that a Wnt activator would be preferable.)
ReplyDeleteMaybe it works for someone else, but this is my experience.
/Ling
Hello, neither mebendazole nor malarone worked for Denis, so Peter what could be the problem, it is something that upsets the immune system and I hope to elucidate this problem. I have not tried invermectin, although I have a box received as a gift from Egypt.. ...In contrast, methyl blue 2-3 drops per day 2-3 times keeps it very well...
Deletedo you use 1% methylene blue solution? I'm thinking of trying too. tell me, and the behavior on it does not deteriorate? increase in hyperactivity and other?
DeleteHello, no actually he calms down and is very calm, even too nice, the anger has completely disappeared, we use 2-3 times a day 2-3 drops of 1% of veterinary use.
DeleteHello, thank you very much, how can I get in touch with Dragos? Thanks
ReplyDeleteHello Tamara, you can find me on Facebook ..... just search for Buga Dragos....
DeleteHi, I recommend using in children with regressive "autism" (MMR Lyme Congenital, Streep) Antiparasitic Pamoate of Pyrantal or Nikvorm a few days depending on the dosage weight and repair at 2-3 weeks.But the star is from everything I have tried so far, and believe me that I have tried a lot, it is a methylen blue, we use it for about a month, he is an autistic child without aggression and hyperactivity, he tries to talk more, as he wants to To say a few words or sentences every day, he wants to love him at bedtime and many new things, he wrap herself at bedtime. I hope to be useful only who has this problem can understand and resonate with us. ..
ReplyDeletethanks for the info. tell me, how long can I take methylen blue? Is it safe to take long term?
DeleteHello, I think that a few drops taken every day could not be a problem, it must be a safe source and not contaminated with metals. Methylene blue has been used for dementia, but also as a good internal disinfectant. Recently it has also been indicated for lyme and co-infections, so you should try to see if you get results. If you are taking ssri antidepressants, please stop them.
DeleteWe have also hit on the combination of pryantel pamoate and propranolol as the most effective thing so far for my son's aggression. I may try the methylene blue as well. His cognitive skills are still slowly declining. From the paper posted above, he seems to fit the hyperactive growth signaling model - Peter, I wonder if you have any suggestions on what to try in that case?
ReplyDeleteHow old is he?
DeletePeter,
ReplyDeleteJust wanted to let you know some interesting news. We just got results back from WES through nebula genomics, and found a tentative hit. It looks to be a mutation on ZNF142, a zinc finger protein gene. Symptoms include most ASD hallmarks but impaired speech and hyperactivity seem to be the two most common behaviors. I actually found it by searching for all the genes identified in children with apraxia of speech, since that is his biggest hurdle. Not much is published about this as it is quite rare.
Hope all is well with you and yours this holiday season~
MKate
SO HOW TO HELP GUY. ZINC SUPPLEMENT ?
DeleteMKate, I did make a quick study and you right that not much has been published about ZNF 142; but there is now interest in this gene.
DeleteThe Iranians published a good study this year.
ZNF142 mutation causes neurodevelopmental disorder with speech impairment and seizures: Novel variants and literature review
https://www.sciencedirect.com/science/article/abs/pii/S1769721222001033
There are also some good older papers.
Recessive variants in ZNF142 cause a complex neurodevelopmental disorder with intellectual disability, speech impairment, seizures, and dystonia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821592/#R17
If I was you, I would make a Facebook page or a website and create a hub for people interested in ZNF 142. Then you become the "official" organization.
Then you can contact the researchers who have already looked at this gene and try and find out how ZNF 142 interacts with other genes and pathways. Then you can ask them for any treatment hunches they have. Iran is actually very active trying out new ideas to treat autism.
When you have gathered more parents and researchers to support you, you can push for a gene therapy to be developed. Post Covid-19 this is much easier, because you use very similar technology to that found in vaccines.
So, Peter, should I understand that if we supplement with zinc, we should see an improvement in hyperactivity and speech?
DeleteHi Peter
ReplyDeleteWhat's your thought about
Loperamide-Anti-diarrhea Medication
https://neurosciencenews.com/anti-diarrhea-asd-medicine-21392/
Riza, yes I saw this when it was first published. Imodium is an OTC remedy for diarrhea.
DeleteIf you do not have diarrhea taking this product will likely cause GI problems. It is interesting but it is not a practical therapy to take every day.
Hello. I did a genetic test "blueprint genetics whole exome" and received as a diagnosis "shashi pena syndrome" mutation on the gene Asxl2 and kcna2. I was told that there is no treatment, his autism would be caused by this mutation. Is there anyone else with this mutation, how can I help him, I read about some enzymes that would repair the genetic changes.
ReplyDeleteDenisa, there is a parent association for people with mutations in ASXL2. They also have a Facebook group.
Deletehttps://www.arrefoundation.org/shashi-pena
Distinct facial features (large head, wide-set eyes, low set ears, birthmarks) are a feature of Shashi Pena syndrome. Does your son have these? It does matter if he does not.
The second gene KCNA2 should be treatable. It encodes the potassium ion channel Kv1.2. In most mutations in ion channels the result is over-expression. This means you can counter the mutation by blocking the affected channel. So you then look for a KV1.2 blocker. I found Dalfampridine, which is a drug approved to treat Multiple Sclerosis under brand names including Ampyra, Fampyra.
Either gene would cause symptoms of autism. It would be good to know which is causal in you son's case.
Normally you will be told exactly the name of the mutation. Some are causal, but others may not be.
Hello Peter. I had chicken pox during pregnancy, I wrote this before in the group, at 22 weeks of pregnancy, I read that this syndrome can also be from a viral infection during pregnancy. When he was little, he had a slightly bigger head and ears a little lower, but they have the normal shape, a hemangioma in the eye that has disappeared, not on the forehead as specified, the eyes are placed normally and are not prominent. Other symptoms that correspond are that he had hypotonia, he was softer, as if he had bones soft, flexible so to speak, fell very easily as if it were gum, delayed speech, delay, behavior problems, aggressiveness, eating problems, eats only certain foods, regression, I put it all on TSA and that's it.. About the second KCNA2 mutation, the doctor said that it wouldn't be there, that if he didn't have convulsions, we'd rather turn our attention to ASLX2. I don't know what investigations to do next. Thank you very much for the answer, the doctor relieved us.
DeleteDenisa, if you click on the link below you will see that 27 different mutations are noted in ASLX2. All the mutations have a name.
Deletehttps://www.malacards.org/card/shashi_pena_syndrome#genetic_variations
Not all mutations cause Shashi Pena syndrome, some cause totally unrelated issues. The doctor should be able to tell you the name of the mutation and if the mutation is pathogenic (ie 100% causal), or of unknown significance. If it is pathogenic then you know it is causal.
Most single gene autisms have a spectrum within them, because there are many different possible mutations and there are other contributing factors.
You might as well try and compare notes with other parents in the Shashi Pena Facebook group and see how your son fits with their symptoms.
Shashi Pena syndrome is caused by a de novo mutation. You would have had to have had chickenpox at the time of conception or earlier for it to influence a de novo mutation. It looks like most de novo mutations are just down to chance. Chickenpox during pregnancy might cause the maternal immune activation type of autism.
Seizures often develop later in childhood. Both genes can cause seizures. KCNA2 has an obvious therapy; for ASLX2 you would treat the symptoms and downstream effects.
Hello, I looked in the test, it has this number: NM_018263.6, benign https://www.ncbi.nlm.nih.gov/clinvar/RCV001270808/ What could mean that he has this syndrome or not, that is, whether or not the mutation on this gene is the cause of his autism? Thank you!
ReplyDeleteWell it would seem to be of uncertain significance. You really need to compare symptoms with the other parents. See if your symptoms are similar, but perhaps milder or completely different.
DeleteNM018263.6 ,c2688A>T,p(Leu896phe)genotype HET,CONSEQUENCE-missense_variant,INHERITANCE-AD,
ReplyDeleteCLASSIFICATION Variant of uncertain signifed,ASSEMBLY GRCH37/hg19,polyphen -benign,MUTTASTER disease causing,PHENOTYPE Shashi-Pena syndrome
Hello, I compared with the other parents, the symptoms are milder, we are dealing with behavioral disorders, oppositional behavior, aggression, language disorders, language delay, cognitive, mild hypotonia, head a little bigger, ears a little lower than normal , teeth demineralization, extractions with general anesthesia from 3 years, regression, constipation, blood sugar fluctuations, sensory problems
ReplyDeleteIt sounds like your son has a mild version of this syndrome. He does share some of the classic features so I think you can say it caused the autism. It was not the chickenpox; that was a coincidence. It was a chance mutation that just happened
DeleteHas anyone established a dosing regiment for vermox and seen any impact?
ReplyDeleteUsed it once for the intended reason and it had no effect. I was expecting a bad effect in our case, but there was nothing. If there was any effect (bad or good depending on how you are wired) with normal dosing it should probably show up in the listed side effects.
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