Autism Drug Effectiveness in Comorbidities

The three autism comorbidities that I have chosen to investigate are asthma, high cholesterol and various types of seizure.

 

Phase 1

The first phase is the easy one.  I just need to see if my autism drugs are proven to be effective in the each comorbidity.  The results really surprised me.

With the exception of bumetanide and asthma, there is a perfect overlap.  Even more surprising, is that another loop diuretic, called furosemide, which is very similar to bumetanide, has been showed to be effective in asthma when given in the inhaled form.

In the case of cholesterol, I am looking at elevated levels in cardiology.  The use of bumetanide in people with heart problems associated with high cholesterol is to reduce blood pressure (anti-hypertensive).

 

 
You can check use of my autism drugs in each comorbidity using Google, or just look at the links I selected below.

 

Asthma/COPD

NAC improves effectiveness of the conventional corticosteroid therapy, particularly in hard to treat cases like current or past smokers. In COPD a severe form of asthma, read:  The role for N-acetylcysteine in the management of COPD

Do statins improve outcomesin patients with asthma on inhaled corticosteroid therapy?

Effect of inhaled furosemide and bumetanide on adenosine5'-monophosphate- and sodium metabisulfite-induced bronchoconstriction in asthmatic subjects

  

High Cholesterol (cardiac treatment)

NAC raises your good HDL cholesterol level, so lowering your overall cholesterol risk factor.

Dose-Related Increase of HDL-cholesterol Levels after N-acetylcysteine in Man

Statins were primarily developed to lower cholesterol as part of cardiac treatment.

 

Bumetanide is a loop diuretic and anti-hypertensive drug primarily marketed as a cardiac drug.

 

Seizures

 Glutathione peroxidase deficiency and childhood seizures

Treatment off our siblings with progressive myoclonus epilepsy of the Unverricht-Lundborg type with N-acetylcysteine

 

Role of Oxidative Stress in Refractory Epilepsy: Evidencein Patients and Experimental Models

 (then click for full version)

Can Statins Lower the Risk for Epilepsy?

Blocking seizures with the diuretic Bumetanide: Promises and pitfalls

 

Phase 2

The second phase involves understanding each comorbidity and seeing if any of their established treatments can be effective in treating autism.

This will also produce some surprises in the following posts.






 

Learning from Comorbidities in Autism

You might have been wondering why there has been a pause in my blog posts; rather than post nonsense, I have been exploring some new directions.

The current combination of bumetanide + NAC + atorvastatin does continue to be effective, but clearly there can be more.

I recently read a paper by a researcher who concluded that he thought autism was so heterogeneous there might well never be a drug therapy for autism.  I certainly see where he is coming from, but I think this tells us two things:-

 

1.      Do not expect conventional medical research to come up with an autism drug any time soon.

 

2.      It would be wise to read up on the medical research outside the realm of autism, where perhaps a more can-do approach and better resourcing might be evident.

This brings me to comorbidities.  In case you are not familiar with this term, in medicine, comorbidity is the presence of one or more disorders (or diseases) in addition to a primary disease.

In the case of autism frequent comorbidities include asthma, high cholesterol and seizures/epilepsy.

I decided to start with asthma, since Monty, aged 9 and with ASD, has mild asthma and I am already familiar with the range of treatments.

I somewhat fancifully hypothesized that there would be an overlap in effective drug therapies for autism and asthma; in other words what works for core autism treatment would be effective in asthma and vice versa.  Having been able to validate my hypothesis, I moved on to look at other comorbidities.  I am currently looking at three areas.

 

1.       Asthma and COPD

Asthma affects 300 million people worldwide and kills about 250,000 people ayear.  COPD (Chronic Obstructive Pulmonary Disease) is a more severe form of asthma and is the third leading cause of death in the US.

I figured that since these conditions are life threatening and widespread in developed counties, they would be well researched and drug therapies actively sought.

2.       High Cholesterol

The effects of high cholesterol are very well studied in cardiology, though not in autism.   The emerging understanding from cardiology is the causal link between cholesterol formation and neuroinflammation.  A little known fact is that elevated cholesterol is the norm in autism; people have asked me why, now I know and soon so will you.

 

3.       Seizures and epilepsy

 It is well known that many people with autism also have epilepsy.  There are many kinds of epilepsy and seizure; two types particularly interested me - absence seizures and non-convulsive seizures.  More of this later.

 

Subequent posts will present what I have learnt.

 

But now for a change of subject  and an interesting link ...

 

Common autism drug therapy in the US

If you do not live in the US, you may be unaware just how many drugs and supplements some autistic children receive.  It seems that in the US, 70% of autistic children take at least 10 different potions.  Not surprising, many of these can interact with each other.

If you are curious to see what some of these drugs are and what the common interactions are, you will find the following paper very interesting.  Its author, Theoharis C. Theoharides, has already appeared on this blog and he will appear again when we look at asthma and immunomodulation.

Unwanted interactions among most common treatment regimes in autism

 

 

 

The Singing Statin, the BCL-2 Gene and Epigenetics

This post has something for both the casual reader and the scientists among you.  Today I will start with the science.

Epigenetics

Epigenetics are chemical markers that can appear on your DNA as the result of some environmental exposure, like diet or stress.  Methylation is a type of epigenetic change in which methyl groups are added to DNA and switch on or off the underlying gene.  This can have severe consequences depending on which gene is affected.

Identical Twins

It seems that if one identical twin has autism, there is a 70% chance that the other twin will be autistic.  In 30% of the cases the twin is neurotypical.  Researchers have very cleverly started to analyse pairs of twins from this 30% group and look for epigenetic marks.  This would highlight genetic causes of autism.

Apoptosis

Apoptosis is a tricky word to spell, for somebody like me, but is actually something quite simple; it is programmed cell death.  Apoptosis happens in all of us, all day long.  If it gets out of control, it becomes bad and something called atrophy will occur.  Too little apoptosis can result in irregular cell growth and cancer.

 

Candidate Genes

Using the epigenetics approach, in 2010 a study was published that identified two “candidate” genes linked to autism.  They were BCL-2 and RORA.

According to that study, BCL-2 is an anti-apoptotic protein located in the outer mitochondrial membrane that is important for cell survival under a variety of stressful conditions.  In other words BCL-2 inhibits cell death.

According to another source, BCL-2 is “one of the foremost anti-apoptotic molecules”.

A very recent study has identified more such genes, using the same approach.

 

If you are really interested in the genetics of autism, there is actually a database of all the indicated genes, maintained by the Simons Foundation.

  

BCL-2 and autism

Going back to 2001, researchers had already noted that the autistic brain was deficient in BCL-2 and they suggested that:-

“These results indicate for the first time that autistic cerebellum may be vulnerable to pro-apoptotic stimuli and to neuronal atrophy as a consequence of decreased BCL-2 levels.”

The study is called :- Reduction in anti-apoptotic protein Bcl-2 in autistic cerebellum

As we have already learned, in the autistic brain the important Purkinje Cells are reduced in number by half due to atrophy.  If BCL-2 can indeed reduce this excessive apoptosis, it should be a friend indeed.

 

Stimulating production of Bcl-2

Fortunately the clever people working with Professor Wood, at the University of Minnesota, have been studying cholesterol regulation in the brain for some time.  Here is what they have been up to:-

“The lab has recently made the novel discovery that statins both in vivo and in vitro stimulate gene expression and protein levels of one of the foremost anti-apoptotic molecules, Bcl-2. Currently, studies are focused on mechanisms of statin-induction of Bcl-2”

Or in plainer English, statin drugs increase your level of BCL-2 and so reduce cell death.
 

If you want to read more here is an open access paper:-  Simvastatin Stimulates Production of the Antiapoptotic Protein Bcl-2 via Endothelin-1 and NFATc3 in SH-SY5Y Cells

 

The Singing Statin

Now we have finished with the pure science and we move back to the practical world of applied science.

Monty, aged 9, has been taking atorvastatin for a few weeks.  After day one, he developed the urge to play the piano outside of lesson time.  Every day since, he has played more and more.  Now his piano teacher says she thinks he has absolute pitch.  It turns out that this is far more common in the autistic population and there is a great deal of research that has been done on this and music/autism in general.  Here is a short article on the subject.

Now in an earlier post we established the importance of the stress hormone cortisol and also the interesting finding that you can reduce it by singing.  Then I got people asking about, “what about just listening to music” or “what about playing an instrument”.  I did not do the research, but I think nothing works like a good sing.

So yesterday I was delighted to hear that Monty has started to sing spontaneously in his room.  He put on his Mozart CD and started to sing, with his own lyrics and not just in English, but also in his second language.

I have to thank Mr Pfizer and in fact Mr Bruce Roth for bringing us Atorvastatin (called Lipitor or Sortis, depending on where you live).  Mr Roth invented it in 1985.

Perhaps BCL-2 could be better named the Singing Gene?

 

 

 

Mixed Media Messages

You may have noticed a week ago SAP, the German software giant, announced that it will in future try to ensure that 1% of its 60,000 workforce are autistic.  This attracted quite a lot of publicity.  It might have been kinder if they had referred to Asperger’s, or at least High Functioning Autism. Not all autistic people are savants or computer wizz kids.

When it comes to TV, the messages are often either trivial or sensational.  But, thanks to the internet, you can access very relevant and intelligent films, and all for free.

The MIND Institute at the University of California in Sacramento, has a rich library of material, from some very well qualified people.

 http://www.ucdmc.ucdavis.edu/mindinstitute/videos/video_autism.html

These films are typically an hour long and cover many of the subjects that have appeared in this blog.  If you are a fan of Temple Grandin, you can even watch her film.  I liked the one by Deborah Fein, halfway down the list.

As usual though, usable conclusions are rather absent; we have to add those ourselves.

 

Belgrade, Busby Babes and the Wakefield MMR Saga

On 5^th February 1958, Manchester United played away to Red Star in Belgrade.  What is remembered is not the match, but the flight home; having stopped to refuel in Munich, the plane crashed on take-off with 23 fatalities and 21 survivors.

Matt Busby, the Manager, survived the accident and ten years later he led a new team of Busby Babes to win the European Cup.  Bobby Charlton and Bill Foulkes survived the crash and played against Benfica in that final.

Why am I telling you about this?  The reason is the air crash investigation that followed.  It was convenient to blame the pilot, Captain James Thain.  The German enquiry blamed him for not deicing the wings and claimed that this ice prevented the plane from taking off, as it reached the end of the runway.

For ten years Thain tried to clear his name and insisted there had been no ice on the wings and that a deep layer of water and slush on the runway caused the accident.  Finally, Harold Wilson, the then British Prime Minister, backed his call for a new investigation.  At that second inquiry, it was shown that Thain had been right all along.  The wings were not iced up, but the runway had not been properly cleaned and the crash was inevitable.  The plane could not gather enough speed to take off and crashed into a house at the end of the runway.

Thain had been a convenient scapegoat and died aged 54, the 24^th victim of the crash.

The truth did come out in the end and it was recently the subject of an excellent documentary by National Geographic.

Do vaccines cause autism?

I was surprised last week when my mother, a retired doctor,  asked whether I thought the MMR vaccination caused autism .  My reply was along the lines of “maybe sometimes, but we will never know”.  A year ago, I would have simply said “of course not”.

Monty, autistic and aged 9, also flies from Belgrade to London, and sometimes via Munich.  Planes have got much bigger and safer and airports are much better prepared for bad weather.  Flying will always have a risk and all drugs have an element of risk; so naturally vaccines also have a risk.

From a public health perspective, it is clear that vaccines save millions of lives and so any risk is vastly outweighed by the overall benefit.

If you were Bill Gates, who is nobly trying to eradicate polio from the planet (he now has the added problem of the Taliban killing the vaccination teams in Pakistan), what would you say about Andrew Wakefield and his linking of autism to vaccines?

Not surprisingly he gets referred to as a fraud and that his research was rigged and that later research proved him wrong.  Now can we get back to eradicating polio!

In the big picture Bill is definitely right; Andrew Wakefield may also be right, but will he ever get a fair chance to prove it?  Captain James Thain waited ten years, I think Andrew Wakefield will need to wait much longer.

It sounds highly plausible that injecting a combination of vaccines preserved in a solution with mercury (the mercury has now replaced by a much larger amount of aluminium) might cause an adverse reaction in the brains of a small number of subjects; perhaps ones with a slightly permeable blood brain barrier (BBB).  Rather than trash this hypothesis, it would have been better to fully investigate it and perhaps develop safer vaccines.  As in Munich, there has been an investigation, but I was rather shocked reading comments of researchers familiar with those studies.

I would agree with Bill that Andrew Wakefield could be seen as a danger to public health, but what if he is also right.  Does it matter?  If you are touched by autism, then yes; otherwise probably not.

Back to Spock

I mentioned a few posts ago that I had been to see the latest Star Trek movie with Ted, aged 12, and his friend Adrian “Mole”.

While saving a planet, but endangering the Starship Enterprise, Spock commented that “the interests of the many outweigh the interests of the few”.  Bill would concur, and so would Peter.

The conclusion is that if you are one of the few, you are on your own.  Do not wait for the Enterprise, or anyone else, to help you.  Help yourself.

I have no idea whether Andrew Wakefield is right, but at least on my blog he gets a chance to present his case. Here he is responding to a recent measles outbreak in South Wales.

Angelina Jolie or Destiny’s Child?

At the time of writing this post Angelina Jolie’s aunt has succumbed to the same cancer that killed Angelina’s mother and she announced that she also carried the same defective gene.  She opted to take pre-emptive action and, in effect, cheat a nasty early death from breast or ovarian cancer.

I have read so much research into autism, that it is pretty clear to me, that you could calculate an Autism Risk Factor (ARF) for prospective parents, if you really wanted to.  Would you really want to?  I expect those with direct experience of autism might be in favour, the others probably would not even bother to answer the question.  Since few truly autistic people have children, it is really more of a question for their siblings; do they want Destiny’s Child?

It may sound depressing, or something to do with eugenics, but actually it does not have to be.  I am not suggesting the sort of genetic and chromosome testing that is already routinely done for conditions like Down’s syndrome.  I am talking about the kind of lifestyle changes that ideally a woman who smokes, drinks heavily or takes drugs, should take when she wants to have a child.

If your ARF puts you at risk, then you would receive a list of lifestyle changes, you should take to minimize the risk to your future child.

 

Autism Risk Factor (ARF)

I am not qualified to develop the ARF, but I am confident enough to highlight two of the factors that should go into it:

 

1.     Maternal & paternal family history of autoimmune diseases

Auto-immune diseases including, but not limited to, history of type 1 diabetes, rheumatoid arthritis, celiac disease and hypothyroidism.  Here is some supporting evidence, for those who are interested:-

·         Association of Family History of Autoimmune Diseases and Autism Spectrum Disorders

 

·         Familial Clustering of Autoimmune Disorders and Evaluation of Medical Risk Factors in Autism

 

2.     Maternal & paternal stress capacity

This risk factor is my invention.  I used to only really think about mechanical stress, but now I know all about physiological stress, psychological stress and that big one, oxidative stress.  It seems, remarkably to me, that the latter three types of stress are in fact one and the same.

Put another way, physiological stress, psychological stress and oxidative stress are reflections of each other.  If you have got one, you will have all three.

The good news is that can use obvious visible cues to spot people will a low stress capacity and you could even then confirm it with a laboratory test of their oxidative stress (GSH redox level).

I recently took four short airplane flights and I observed people with chronic nail chewing (male) and obsessive nail filing (female) sitting beside or in front of me; it looks like about 5% of the flying population.  If you added the non-autistic people with mild stereotypy (stimming) like foot flapping, and those with Trichotillomania (compulsive hair pulling, that we learned about in the posts on GSH/NAC) you would have a large proportion of those people living in some degree of potentially damaging oxidative stress.

I think the maternal stress capacity would be most relevant, but the fetus’s own stress capacity is also important, and some of that clearly comes from the paternal side.

Conclusion

So the conclusion for Ted, aged 12, is to grow up and find a nice calm girlfriend and buy a large supply of NAC, just in case.

 

 

 

The Swedish Disease

Ted, (aged 12, and supposedly “normal”) and his brother Monty (aged 9, and now steadily becoming more “normal”, as this blog progresses) go to the same school as a Swedish family.  In Ted’s class is a Swedish girl, Charlotte, and her younger brother is in the Primary school along with Monty.  I have been both surprised and impressed, by how nice the kids in Primary are to kids with any kind of special need.  However, once they make the big leap to Secondary, they stop being so nice; it becomes cool to be critical and even cruel.

Ted’s Swedish friend, Charlotte, was explaining to their class that her younger brother had something called Attention Deficit Hyperactivity Disorder, but it was OK, because he only had 10% ADHD.  Ted of course then replied “and you have got the other 90%”.  Some of the other things they get up to are far, far worse; one reason why I put Monty down a couple of years in Primary.

But, the Swedish Disease is not ADHD.

During my research, I recently came across some references to so-called “Somali autism clusters”; this caught my attention and so I decided to delve deeper.

It seems that following the descent of Somalia into becoming a failed state, many refugees have been welcomed by the United States and Sweden, in particular.  In the US there are now communities living in Minneapolis and San Diego.  Not long had they arrived in their new homeland, when they started to produce large numbers of autistic children; sounds odd does it not?

Swedish researchers got on the plane to Minneapolis in the US, to launch a joint investigation and it was reported that Dr Wakefield wanted to go to San Diego to investigate.  The Swedes did not come up with an explanation that convinces me.  I think I have a much better one, and one that Dr Paul Ashwood, from the University of California might agree with.

The Swedish Somalis said they had never encountered autism before and so they named it the “Swedish Disease”.  The Swedish researchers concluded that since both Sweden and Minneapolis are far north, where the sun does not shine so much, the autism was the result of a lack of vitamin D.  That sounded odd to me; what about the cluster in San Diego that Dr Wakefield wanted to get in touch with?  Last time I was in California, the sun hardly ever went away.

A much more likely explanation is related to the immune system.  I have never had the pleasure of touching down in Mogadishu (the capital of Somalia, in case you did not know) but I did travel extensively in some poorer parts of Asia.  The level of hygiene and cleanliness in rural parts of India would really shock most westerners; the most effective strategy is just not to eat anything.  I came back 9 pounds lighter.

In my recent posts, I showed how the immune system plays a major role in the predisposition of children to autism; to me it is hardly surprising that first generation Somali children, born in ultra-clean Sweden and America, have a high incidence of disease related to the immune system, and to neuroinflammation in particular.  I dare say they never had much asthma in Somalia either.

The parents’ immune system has been toughened by all manner of parasites, bacteria and virus and has no doubt evolved to be prepared for it.  The children inherited their parents’ immune system, but it has stopped being challenged by any kind of serious attack.  Then in utero, or in very early childhood, a big oxidative shock came along and the immune system went crazy and over-reacted (a cytokine storm); massive neuroinflammation caused permanent brain damage and autism was the result.

It’s just my theory, but if you ever read that Somali immigrants are complaining about asthma and food intolerance, it might just be right.

More recently, the Swedes did a very large study looking at autism in all their immigrant population, here is an interesting link discussing the study:- 

Swedish study dissects autism risk in immigrants

 

A Cytokine Storm? Mr Spock

I have recently started learning the workings of the human immune system, while 12 year old Ted (“normal” except for a Star Wars obsession) has been discovering Star Trek.  Last weekend we went to the cinema with Adrian “Mole” to see the latest release.  Mr Spock made one interesting observation, regarding what can happen when the interests of the many outweigh the interests of the few; this will be the tittle of a forthcoming post about the fate of Dr Wakefield and his vaccine theory.

Cytokines

Cytokines really do exist, even though they sound like something from science fiction.  They are signalling molecules associated with inflammation.  Several inflammatory cytokines are induced by oxidative stress.  The fact that cytokines themselves trigger the release of other cytokines and also lead to increased oxidant stress, makes them important in chronic inflammation.  In extreme cases, there is a downward spiral of inflammation making it worse and worse.  The Spanish Flue in 1918 and SARS in 2003 are given as examples of such deadly cytokine storms.

The Research

There is a vast amount of research about the role of cytokines in autism and some very good work has been done by Paul Ashwood.  Finally, I have found an Englishman, even though he has gone to live in California, publishing some really high quality and useful research.  It turns out he is a colleague of Dr Wakefield.  Much of Paul Ashwood’s research is not available for free.  This one is:-  The role of immune dysfunction in the pathophysiology of autism

This paper is very readable and shows how a dysfunction of the immune system is without doubt a major part of the autism story. In typical post-Wakefield fashion, nobody wants to stick their necks out and draw usable, if only hypothetical, conclusions; it is easier to just suggest further research.

All the research shows high levels of cytokines in autistic subjects in the brain, spinal fluid, blood and in the gut.  Recent research also shows high levels of cytokines in the siblings of autistic people:- Plasma cytokine profiling insibling pairs discordant for autism spectrum disorder

The researchers comment:-

Thus, the lack of significant differences between sibling pairs discordant for ASD found in our study is in line with the results of previous studies. It is possible that a common immunogenetic background shared by siblings might eventually lead to different clinical outcomes when an environmental stress (for example, prenatal exposure to environmental toxins, viral and bacterial infections, parental microchimerism, etc.) occurs during development.

This last finding was deftly understood by 12 year old Ted, who commented, “Well Dad, you nearly had two autistic children”

Well isn’t he a chip off the old block.

Peter Interpretation

So combining this knowledge with my other readings, drew me to the logical conclusion that the inherited immune dysfunction, combined with the oxidative shock, so well described by Chauhan et al,(in the 400 page book) most likely resulted in a cytokine storm that damaged the brain, and autism resulted.  Due to the feedback loop of the cytokines, the neuroinflammation continues for life.

This then led me to research cytokine storms, to see how the cycle could be stopped and some kind of homeostasis reinstated.  I did not expect to find an answer, but I did.   

First we have to introduce new terms, TNF and TNFR.

TumorNecrosis Factors (TNF)

Tumor necrosis factors (or the TNF family) refer to a group of cytokines whose family can cause cell death or apoptosis.  19 members of the TNF family have so far been identified; the one that caught my eye was OX40L, a cytokine that co-stimulates T cell proliferation and cytokine production.

A tumor necrosis factor receptor (TNFR), or death receptor, is a cytokine receptor that binds TNFs.  The matching TNFR for the TNF OX40L is called OX40 (also known as CD134).

OX40 binds to receptors on T-cells, preventing them from dying and subsequently increasing cytokine production. OX40 has a critical role in the maintenance of an immune response beyond the first few days and onwards to a memory response due to its ability to enhance survival. OX40 also plays a crucial role in both Th1 and Th2 mediated reactions in vivo. T helper cells (type 1 and 2) are white blood cells that play a major role in the immune system
OX40 has been implicated in cytokine storms.

Cause of the Cytokine Storm

When the immune system is fighting pathogens, cytokines signal immune cells such as T-cells and macrophages to travel to the site of infection. In addition, cytokines activate those cells, stimulating them to produce more cytokines.  Normally, this feedback loop is kept in check by the body. However, in some instances, the reaction becomes uncontrolled, and too many immune cells are activated in a single place. The precise reason for this is not entirely understood but may be caused by an exaggerated response when the immune system encounters a new and highly pathogenic invader. Cytokine storms have potential to do significant damage to body tissues and organs.

TNF inhibitors and Cytokine Storms

The cytokine storm is kept going by the TNF cytokines.  So if these cytokines could be inhibited the storm might abate. An existing medication developed for arthritis called a TNF-alpha blocker was proposed as a possible drug. Corticosteroids and NSAIDS (Non-steroidal anti-inflammatory drugs) have been found ineffective.

In 2003 researchers at Imperial College demonstrated the possibility of preventing a cytokine storm by inhibiting or disabling T-cell response. A few days after T cells are activated, they produce OX40, a "survival signal" that keeps activated T-cells working at the site of inflammation during infection with influenza or other pathogens. OX40 binds to receptors on T-cells, preventing them from dying and subsequently increasing cytokine production. A combined protein, OX40- immunoglobulin (OX40-Ig), a human-made fusion protein, prevents OX40 from reaching the T-cell receptors, thus reducing the T-cell response. Experiments in mice have demonstrated that OX40-Ig can reduce the symptoms associated with an immune overreaction while allowing the immune system to fight off the virus successfully. By blocking the OX40 receptor on T-cells, researchers were able to prevent the development of the most serious flu symptoms in these experimental mice.  Sadly, it appears this discovery has been abandoned by the small company that tried to develop it.

And now for the shock …

In 2009 researchers in China found that a statin induced down-regulation of OX40 and OX40L in a concentration-dependent manner.

Simvastatin reduces OX40 and OX40 ligand expression in human peripheral blood mononuclear cells and in patients with atherosclerotic cerebral infarction.

"These findings improve our understanding of the anti-inflammatory and immunomodulatory properties of simvastatin"

Antioxidants have been successfully trialled in cases of Acute Respiratory Distress Syndrome (ARDS), which is another example of cytokine storm.  Organ damage was reduced and there was an improved survival rate.

Conclusion

It would seem that the combination of antioxidant and statin is about as good a combination as is currently possible, to dampen down the remaining effects of a cytokine storm, which is the extreme case of neuroinflammation.

By skill, or luck, this combination is exactly what I am trialling with Monty.