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Showing posts with label parasite. Show all posts
Showing posts with label parasite. Show all posts

Wednesday 30 November 2022

Repurposing Anti-parasite drugs to treat Cancer and Autism?

 

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.

 https://maayanlab.cloud/Harmonizome/gene_set/pyrantel-5513/CMAP+Signatures+of+Differentially+Expressed+Genes+for+Small+Molecules

 

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: 


Antiparasitic and Antifungal Medications for Targeting Cancer Cells Literature Review and Case Studies Frederick T. Guilford, MD; Simon Yu, MD

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


 Conclusion

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.






Thursday 17 August 2017

Viruses, Bacteria, Fungi, Parasites and Altered Gene Expression, Relevant to Autism






Today’s post started life as a review of how some viruses affect gene expression and may help cause, or just trigger flare-ups in, some neurological disorders ranging from autism to MS (multiple sclerosis). 
Some people with autism are treated with anti-viral drugs and, anecdotally, some do respond well.  This is not yet an area with hard facts and definitive clinical trials.  
It is actually better to first take a few steps back and consider how all microorganisms can play a role in human health by modifying the gene expression of the host (which is you).  There are four broad categories of microorganism.
Each type of microorganism can be countered by a matching category of pharmaceutical.

·        Antibacterials/antibiotics for bacteria

·        Antifungals to kill or prevent further growth of fungi

·        Antivirals to minimize (but often not eradicate) viruses

·        Antiparasitics to kill parasites  (protists)

All of the above categories of microorganism can affect the expression of multiple genes. By either up or down-regulating important genes at critical times during development, long lasting effects can be created, or there may be just transient effects.
Changes in gene expression likely play a role in many neurological conditions and in particular in what I call “flare-ups”, for example in autism, PANS, PANDAS and indeed schizophrenia.
Not all changes in gene expression are bad. The TSO parasites that do seem to help some people’s autism, by down regulating their immune response, very likely are modifying the host’s gene expression, which then reduces their immune response. This is the mechanism developed by the parasite to protect itself from the host (you) and ensure it is not eradicated.
Steroids affect the expression of multiple genes. When a bacteria of virus triggers PANDAS/PANS the positive effect of steroid therapy may well be by “resetting” the expression of certain important genes.  Here again, even though PANDAS/PANS is now treated clinically in the US, much remains unknown.
For those interested, earlier this summer revised treatment guidelines were published for PANDAS/PANS.

In "
Part I–Psychiatric and Behavioral Interventions," Margo Thienemann, MD, Stanford University and coauthors present consensus guidelines for treating the psychiatric and behavioral symptoms of children with PANS/PANDAS. Symptom improvement is aimed at decreasing suffering, improving functioning, and making it easier for the children to adhere to therapeutic interventions.

In "
Part II–Use of Immunomodulatory Therapies," Jennifer Frankovich, MD, and coauthors provide recommendations to help guide the use of therapies targeting the neuroinflammation and post-infectious autoimmunity that are common in PANS-PANDAS.

In “
Part III–Treatment and Prevention of Infections," Michael Cooperstock, MD, MPH, University of Missouri School of Medicine (Columbia) and coauthors representing the PANS PANDAS Consortium, present a consensus guideline for managing the infection components of these neuropsychiatric conditions.

There is research on what virus/bacteria affects which specific gene, but this area of science is in its infancy.
MS (Multiple Sclerosis) a condition that features faulty remyelination, is likely a much simpler condition than autism and yet nobody knows for sure what causes it. It has been suggested that a virus may be the trigger of at least some types of MS, but researchers are decades away from proving anything. So when it comes to microorganisms and autism, it is mainly a case of speculation and the odd N=1 case study. 

Viral triggers of multiple sclerosis 


The relationship between infections and autoimmune diseases is complex and the mechanisms by which infectious pathogens could trigger MS are likely dynamic, i.e., they might change over time and not be mutually exclusive. Epidemiological observations indicate that viral infections could contribute to MS development not only as triggers of disease exacerbations but also as etiological agents, i.e., long before the disease becomes clinically apparent. The two- to three-folds increased risk of developing MS among individuals with history of IM compared with subjects who acquired EBV without symptoms, the almost universal seropositivity for EBV in adults and children with MS, and the steep and monotonic increase in MS risk with increasing titers of antibodies to EBV in apparently healthy adults could suggest that EBV infection is causally linked to MS development. The mechanisms responsible for this association are far from understood. Moreover, the incidence of IM in Western countries (≥ 5%)  exceeds the prevalence of MS in comparable populations (0.1%) by far (more than 50-fold) suggesting that yet unidentified genetic and/or additional environmental factors determine whether symptomatic EBV infection indeed predisposes to MS.

Although one particular MS-causing agent might still be discovered, current data suggest that multiple infections along with noninfectious environmental factors trigger the development of MS. These factors are likely ubiquitous, i.e., highly prevalent in the general population, and they require a permissive genetic background that predisposes for MS development. Future studies investigating infectious pathogens in a complex and heterogenous disease such as MS will benefit from careful and detailed clinical, pathological, and neuroimaging-based patient characterizations and from reproducibility in different study populations. In addition, novel humanized animal models of autoimmune diseases that are simultaneously permissive for viral pathogens which usually infect only humans  should allow investigation of specific aspects of host–pathogen interactions during autoimmune CNS inflammation in vivo. The integration of these data might eventually allow us to better define the role of viruses in the etiology and pathogenesis of MS and how virus–host interactions could be targeted for MS therapy.  

The ubiquitous human herpesvirus 6 may play a critical role in impeding the brain's ability to repair itself in diseases like multiple sclerosis. These findings may help explain the differences in severity in symptoms that many people with the disease experience
What is still not fully understood is the relationship between the extent of the viral infection in the brain and the severity of diseases like multiple sclerosis and other demyelinating diseases such as leukodystrophies and Vanishing White Matter disease. For example, do the number of infected cells need to reach a certain threshold before OPC function is impeded? Are individuals who have congenital HHV6 more vulnerable to severe forms of these diseases?
"More research is needed to understand by which mechanisms the virus impedes the function of OPCs and what impact this has on the progression of these diseases," said Mayer-Proschel. "But it is clear that HHV6, while not necessarily the cause of demyelinating diseases, is limiting the ability of the brain to repair damage to myelin thereby potentially accelerating the progression of these diseases."  

Mainstream and “Alternative” Research  
Not all published research fits with the current mainstream scientific consensus. The mainstream is clearly moving towards the realization that all kinds of things can affect gene expression. One currently fashionable area is the gut microbiota, as in this article:-

Some researchers develop hypotheses that go much further, like this one regarding autism’s elder brother, schizophrenia.


Many genes have been implicated in schizophrenia as have viral prenatal or adult infections and toxoplasmosis or Lyme disease. Several autoantigens also target key pathology-related proteins. These factors are interrelated. Susceptibility genes encode for proteins homologous to those of the pathogens while the autoantigens are homologous to pathogens' proteins, suggesting that the risk-promoting effects of genes and risk factors are conditional upon each other, and dependent upon protein matching between pathogen and susceptibility gene products. Pathogens' proteins may act as dummy ligands, decoy receptors, or via interactome interference. Many such proteins are immunogenic suggesting that antibody mediated knockdown of multiple schizophrenia gene products could contribute to the disease, explaining the immune activation in the brain and lymphocytes in schizophrenia, and the preponderance of immune-related gene variants in the schizophrenia genome. Schizophrenia may thus be a “pathogenetic” autoimmune disorder, caused by pathogens, genes, and the immune system acting together, and perhaps preventable by pathogen elimination, or curable by the removal of culpable antibodies and antigens.

And this one by the same author:-

Herpes simplex virus 1 (HSV-1) can promote beta-amyloid deposition and tau phosphorylation, demyelination or cognitive deficits relevant to Alzheimer's disease or multiple sclerosis and to many neuropsychiatric disorders with which it has been implicated. A seroprevalence much higher than disease incidence has called into question any primary causal role. However, as also the case with risk-promoting polymorphisms (also present in control populations), any causal effects are likely to be conditional. During its life cycle, the virus binds to many proteins and modifies the expression of multiple genes creating a host/pathogen interactome involving 1347 host genes. This data set is heavily enriched in the susceptibility genes for multiple sclerosis (P = 1.3E-99) > Alzheimer's disease > schizophrenia > Parkinsonism > depression > bipolar disorder > childhood obesity > chronic fatigue > autism > and anorexia (P = 0.047) but not attention deficit hyperactivity disorder, a relationship maintained for genome-wide association study data sets in multiple sclerosis and Alzheimer's disease. Overlapping susceptibility gene/interactome data sets disrupt signalling networks relevant to each disease, suggesting that disease susceptibility genes may filter the attentions of the pathogen towards particular pathways and pathologies. In this way, the same pathogen could contribute to multiple diseases in a gene-dependent manner and condition the risk-promoting effects of the genes whose function it disrupts.

Back to Autism
As we have seen previously in this blog, autism is usually polygenic, meaning very many different genes are affected. This does not mean that anything is necessarily defective in those genes, it just means those genes are either over or under-expressed, this means you end up with either too much, or too little, of whatever that gene makes.
So for a polygenic condition, where in one person hundreds of your 22,000 individual genes are likely over or under-expressed, we really do not want anything to come along and further miss-express critical genes.
Many genes are inter-related and so miss-expression of one can trigger a wave of further effects. This can be either good or bad.
The science is still in its infancy, so it will be many decades before it is translated into medicine, but we can certainly already say what may be happening.
The interactome is a relatively new word to describe the whole set of molecular interactions in a particular cell.
 For example, the well-known bacteria H.pylori that can cause stomach ulcers:- 

Over 1,200 interactions were identified between H. pylori proteins, connecting 46.6% of the proteome.

Just this one common bacterium affects half of the entire set of proteins expressed by a genome (the so called proteome).
So we should not be surprised if some bacteria or viruses have a bad, or indeed good, effect on autism.
This also bring us back to the idea of the holobiont and hologenome, which was introduced in an earlier post. The idea is that what really matters in human health is not just your genome, but the totality of what surrounds you, so that means everything living in you, on you and around you. That includes bugs, bacteria and also those of your pet dog.
All of these factors influence how your genes are expressed. During evolution your body has got used to things and if you make rapid changes, you may indeed upset the balance. So while chlorinating water may have an overall good effect, by killing all those bacteria your body had been expecting, there may be some negative effects. Humans evolved living close to animals, be it dogs or farm animals. We saw earlier that pregnant mothers who live with pets produce children with a lower incidence of asthma.
We also reviewed the hygiene hypothesis, which basically says that a bit of dirt is good for you.
So this post, rather than narrowing things down, really broadens them out.  Everything affects everything.  If you rock the evolutionary boat, don’t be surprised if strange things happen.
Taking Somali refugees to live in Sweden increased their incidence of autism. Is that really a surprise? Recall the Somali autism clusters in Sweden and San Diego.
Apparently, the Amish in the US have a low prevalence of autism. Is that really a surprise?  One reader recently suggested sending autistic people to live with the Amish, as a therapy. The possibly effective therapy would have been to send the parents to live with the Amish for a couple of years before the child was born.
So perhaps we should consider much autism, and indeed conditions like asthma, as collateral damage from modern living?  Life expectancy has risen, infant mortality has been greatly reduced, but the downside is that we now have much more autoimmune disease and that includes autism.

Autism and Microorganisms
Now back to autism and the four categories of microorganism.
Can parasites cause autism? Actually we know they can; for example cerebral malaria can result in it. But how often is this case? Probably very rarely.
Can fungi cause autism? Perhaps, but we know from many examples (including in the comments on this blog) that some fungi can make autism worse.  Is the fungus candida albicans growing in the intestines really an issue in most autism? I seriously doubt it, but oral thrush/candidiasis caused by inhaled steroids does seem to make autism worse and is reversible by removing the fungus. The effect seems more likely to be from the candida than the steroid, since inhaled steroids only mildly enter the bloodstream.
Can bacteria cause autism? Well streptococcus bacteria can cause OCD and cognitive impairment (PANDAS).
Can a virus cause autism? Antonio Persico, one of the more serious autism researchers, has suggested that some autism may be caused by polyomaviruses transmitted at conception from father to mother.
https://spectrumnews.org/news/could-a-virus-cause-autism/

Can the rubella virus cause autism? Some serious people do see a possibility, even in people who have been vaccinated.

These both remain controversial hypotheses; but can viruses cause flare ups in autism, later in life? This is also controversial, but I think quite plausible.  It all depends which genes the virus causes to get miss-expressed.
Enough is known to say that odd changes in autism may potentially be triggered by the appearance of specific types of microorganism, but quite possibly most microorganisms have little, or no, negative effect in most people. So it is not a case of all viruses/bacteria will make autism worse, but it is likely true that some may have the potential to do so.
In trying to figure out possible causes of autism flare-ups, due consideration should be given to microorganisms.  This is another case of personalized medicine, with all its potential pitfalls.
The big risk is potentially becoming obsessed with non-existing bacteria, viruses, fungi or parasites.  


Back to Antivirals and Autism 
Finally we come back to where the original idea for this post came from; is there any basis of the use of antiviral drugs to treat autism?
DAN-type doctors do prescribe the antiviral drugs Valtrex, Famvir or Acyclovir.


Antiviral drugs do not destroy their target virus they just inhibit its development.
Most of the antiviral drugs now available are designed to help deal with HIV, herpes viruses, the hepatitis B and C viruses, and influenza A and B viruses.
You identify a virus by looking for antibodies to that specific virus in the blood. You can test for antibodies that suggest if the infection is new and active, called IgM antibodies and you can test for antibodies that show the infection occurred sometime in the past, called IgG antibodies.
You would need to know which virus to test for, the common ones are:-

HSV 1:  Herpes Simplex Virus 1 causes canker sores in the mouth

HSV 2: Herpes Simplex Virus 2 causes genital herpes.

HHV 6: Human Herpes Virus 6 is commonly known as Roseola virus

EBV: Epstein-Barr Virus, causes the illness known as infectious mononucleosis

Measles

Rubella  


“We’re not saying that HSV-2 is responsible for infecting the [fetal] brain and causing autism,” stresses senior author Ian Lipkin, an infectious disease expert and epidemiologist at Columbia. Indeed, fetal infection with HSV-2 is so serious that it frequently leads to miscarriages or stillbirths. Rather, Lipkin suspects that HSV-2 is just one among many environmental insults that, when they arrive at a vulnerable point in fetal development in women predisposed to damaging reactions, may trigger ASD in the fetus.” 

Conclusion: Rate of contact with HSV1 and HSV2 assessed by the mean of detection of specific antibodies was similar between children with ASD and healthy controls.

Conclusion: Levels and seropositivity rate of antibodies to HHV-6 and HHV-8 do not differ between children with ASD and controls.
CONCLUSION: Titre and seropositivity rate of antibodies to CMV and EBV are similar between children with ASD and healthy controls.


Valtrex 
Valtrex seems to be the antiviral most commonly prescribed in autism.  This is an off-label use, meaning Valtrex is not approved to treat autism.  Valtrex is active against most species in the herpesvirus family. In descending order of activity:

So we might assume the people with autism who respond to Valtrex might have one of the above, or similar, viruses. Unless Valtrex has some other modes of action, unrelated to being an anti-viral, which remains a possibility. 

Mitochondrial Disease and Viral Infections
Since this post is already full of speculation, I will add some more. Some people say that their child’s mitochondrial disease was preceded by a viral infection, so how likely is it that a virus can trigger mitochondrial disease and then autism?  Again, this is not something anyone can prove, one way or the other, but it does look like your mitochondria are particularly vulnerable to viruses.
The virus will exploit the mitochondria to further its own development, perhaps in doing so, in some people with a pre-disposition, this triggers a process to chronic mitochondrial dysfunction.  Read the papers below for more on this subject.


Highlights


Mitochondrial dynamics influences mitochondrial and cellular functions.
Mitochondrial dynamics is affected during viral infections.
Viruses exploit mitochondrial dynamics and mitophagy to benefit infectious process.
Virus-altered mitochondrial dynamics determines the outcome of infection.
Disruption of mitochondrial dynamics promotes viral pathogenesis.

If a virus can trigger mitochondrial disease, as we have seen a vaccination can, is there any possible merit in using antivirals years later?
Is there merit treating regressive autism, which is likely to be mitochondrial disease, immediately with antiviral drugs?
Is there merit treating autism flare-ups, that do not respond to PANDAS/PANS therapies, with antiviral drugs?
Is there merit treating MS (multiple sclerosis) immediately on diagnosis with antiviral drugs? Would MS flare-ups respond to antivirals?

My take
If I was to develop MS tomorrow, given there is currently no cure, I think I might want to try an antiviral, just in case it might actually do some good.
My son with classic autism did have a PANDAS-like regression last year, with sudden onset OCD and strange verbalizations. It all went away after a couple of weeks, having been treated as a PANDAS flare-up, as documented in an old post on this blog. If after a viral infection he developed a sudden onset regression I would certainly reread this post.
Readers of this blog with a clear case of mitochondrial disease might want to check for the commonly implicated viruses, since if one was never suppressed this might be something to consider.
So do antivirals have a place in treating autism?  There is no hard evidence to support their use, but I would not at all be surprised if a minority do genuinely benefit. I think the most likely group might be those who have a sudden regression from near typical. As with PANDAS/PANS, the sooner the treatment commences, the better the likely outcome. 
Could antivirals help control flare-ups that can occur in those already with autism? They could well help; ideally you would confirm the presence of the virus first.   

Conclusion
I recently watched an expert clinician talking about irritable bowel syndrome (IBS); he was very open about his opinion that science likely only understands about 30% of the disorder. When it comes to autism I think science may be only at the 10% mark. As a result you have to be very careful about saying anything definitive.
We know that very many things contribute to the prevalence of autism.  It looks more than likely that viruses, bacteria, fungi and parasites may, on occasion, play a role in some people’s autism.
But, just like we know that in some people vaccination can trigger mitochondrial disease and result in an autism diagnosis, this does not mean it is a common cause of autism. Vaccinations have saved hundreds of millions of lives, but it has long been known that they can have side effects and that is why there is a large industry-funded compensation scheme in the US.
So while parasites can in some circumstances lead to autism, this does not mean feeding bleach to children with autism is a clever idea. Nor does filling them with antibiotics to treat a non-existing bacteria.
You can see why mainstream medicine is not eager to treat autism.
Nonetheless, applying that meagre sounding 10% of understanding can yield results, when applied with caution.