Steroids for Regressive Autism

As we have seen at various points in this blog, there is mounting evidence to support the use of steroids in autism, particularly in regressive autism.

Since long-term steroid use has side effects, there have been no large long-term trials.  There is plenty of anecdotal evidence, particularly from the US.  We saw a paper on Immunomodulatory Therapy, by Michael Chez, which discussed the benefits of Prednisone, a very cheap oral steroid.

Immune Therapy in Autism: Historical Experience and Future Directions with immunomodulatory Therapy

In the days before inhalers for asthma, it was low dose oral prednisone that kept many sufferers from an early death.  It did result in reduced height, but this is probably a price worth paying to stay alive.

A paper was recently published by specialists at Harvard Medical School on the subject of steroids and regressive autism.

Corticosteroid therapy in regressive autism: a retrospective study ofeffects on the Frequency Modulated Auditory Evoked Response (FMAER), language,and behavior

It pretty much concludes the same as Chez and others have been saying for many years; corticosteroids can have a profound effect on some types of autism.  It remains unlikely that there will ever be large scale trials, due to the scaremongering about side effects.  Much is known about how to minimize the side effects of steroids, for example tapering and pulse dosing.

Here are some key points from the paper:-

·        Up to a third of children with Autism Spectrum Disorder (ASD) manifest regressive autism (R-ASD).They show normal early development followed by loss of language and social skills. Absent evidence-based therapies, anecdotal evidence suggests improvement following use of corticosteroids

·        Twenty steroid-treated R-ASD (STAR) and 24 not-treated ASD patients (NSA), aged 3 - 5 years, were retrospectively identified from a large database.

·        Star group subjects’ language ratings were significantly improved and more STAR than NSA group subjects showed significant language improvement. Most STAR group children showed significant behavioral improvement after treatment. STAR group language and behavior improvement was retained one year after treatment. Groups did not differ in terms of minor EEG abnormalities. Steroid treatment produced no lasting morbidity

·        Steroid treatment was associated with a significantly increased FMAER response magnitude, reduction of FMAER response distortion, and improvement in language and behavior scores. This was not observed in the non-treated group. These pilot findings warrant a prospective randomized validation trial of steroid treatment for R-ASD utilizing FMAER, EEG, and standardized ASD, language and behavior measures, and a longer follow-up period.

·        Referring physicians often enquire about the utility of adrenal corticosteroids or glucocorticoids to treat patients with R-ASD

Prednisone is already a treatment used in PANS, PANDAS and Landau-kleffner syndrome, which all have autism-like symptoms.

Corticosteroids for the treatment of Landau-kleffner syndrome and continuous spike-wave discharge during sleep.

  

'Wicked'

Slightly off-topic but, the following is relevant.  

There was a recent documentary by the BBC about US-style DAN autism therapies now being sold to parents in the United Kingdom.  The UK has a government funded institute (NICE) that publishes lengthy advice to doctors as to what drugs to prescribe for almost all conditions, including autism. UK doctors will get into trouble if they do not follow NICE guidelines.

Commenting for the BBC, on the DAN-type treatments, Francesca Happe, a professor of cognitive neuroscience at King's College London and apparently one of the world's leading researchers into autism, said practitioners who "peddled" treatments without proof were "wicked".

But how much proof do you need?  And who is to say which published researcher is serious and which is a charlatan.  The lay autism parent might (falsely) assume that if a researcher is publishing papers, they must be serious and the conclusions reliable.  The reality is that some of the papers are indeed flawed and the conclusions are nonsense.  That is why I keep a list of the researchers who I believe in.

At the extreme are bodies like the UK’s NICE, who conclude that absolutely none of the hundreds/thousands of drugs/supplements proposed for treating core-autism should be used.

The short version of the NICE clinical guidelines is below.  The much longer version reviews in detail many of the papers I have reviewed in this blog, but comes to a very different conclusion.

The management and support of children and

young people on the autism spectrum

I read the same papers as NICE and concluded something entirely different.  I found several drugs that do indeed work.  The difference is that my standard of proof is lower than that of NICE and professor of cognitive neuroscience at King's College London.

The DAN/TACA/MAPS/ARI doctors from the US are also hopefully read all these papers, but they come up with ideas of the sort that do fall into the “wicked “category mentioned above.  

Autism parents are not surprising bewildered.  It is the parent that ends up deciding where to draw the line between what treatment is genuine and what is fantasy, perhaps like this one.

Conclusion

Yet again, we have a therapy based on solid science that is in use by a very small number of serious mainstream doctors.  It has not crossed into general use due to a lack of large scale trials.

As a result, medical science continues to tell families that there are no drug therapies for core autism, except some anti-psychotics, anti-depressants and anticonvulsants most of which have serious side-effects and/or cause dependence.

In the case of prednisone, this is a cheap generic drug that does have side effect with prolonged use.  Severe regressive autism can also have side-effects, like complete loss of speech and cognitive impairment.

The answer might be parents signing a waiver to get open access to drugs that have been used successfully in experimental use for autism, without the doctor worrying about losing his license, or being blamed for any side effects.

PANDAS, PANS, Penguins and Autism

Anyone with a serious interest in autism should also be aware of PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) and PANS (Pediatric Acute-onset Neuropsychiatric Syndrome).  These are two syndromes which have acute onset of symptoms very similar to some of those found in autism.  It is claimed to affect 1 in every 200 children in the US.

The good news is that a very thorough and dedicated doctor called Susan Swedo has worked logically through from starting to identify the syndrome, all the way through to treating it.  Good job Susan.

Though she insists that PANDAS and PANS are distinct from autism, one can only wonder how many other distinct, but yet to be identified, syndromes exist that also present with autism-like symptoms.

Thanks to the efforts of Dr Swedo and the US NIMH (National Institute of Mental Health), these two conditions have been remarkably well investigated, in a very short period of time.  It shows what medical science can achieve when the right people are in charge.  It is odd that such effective clinical attention has not been focused on autism itself.

Here is a very recent presentation given by Dr Swedo, which really covers all the important aspects of both PANS and PANDAS.  For those with a serious interest, have a look though this post and then watch the presentation, to get the most from it.

Dr Susan Swedo (click for IPad users)

Penguins and PANDAS

One of the reasons I was so impressed by how PANDAS has been addressed, as opposed to the much more common autism, is the before and after data.  For example, many people talk about regressive autism, but nobody quantifies from what, to what.  Some children went from a spoken vocabulary of 10 words to 2 words, while others went from 500 words to zero; there is a profound (and relevant) difference.

In the case of PANS and PANDAS we have the before and after artwork from the affected kids. As usual, a picture is worth a thousand words.

I have no great panda pictures, but Monty aged 10 with ASD, brought back his artwork from school last week and pride of place goes to his picture of two penguins.  We were all more than a little taken aback to see it.  Did he really draw this? Unassisted?  It looks much more like the work of his big brother.  Even his assistant was surprised and confirmed that this was the result of his work in the art room for a double lesson.  I never expected to be displaying Monty’s artwork to the world.

Later in this post you will see the before and after PANDAS artwork.

PANDAS and PANS

When I first came across a condition known as PANDAS or PANS, I did not take that much notice; with such a name I assumed it was nonsense.   Researchers should give a serious syndrome a serious name/acronym.

I imagine that with the ever widening of the diagnosis of autism, some people with PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) /PANS (Pediatric Acute-onset Neuropsychiatric Syndrome) have been misdiagnosed as autistic and vice versa.

When you look at the symptoms and apparent cause of PANDAS/PANS you may wonder how many other similar conditions exist within the myriad of conditions leading to autism.

The shocking regression in cognitive function (illustrated by children’s drawings further down the page) produced by this condition and the fact that it can be reversed, should really be carefully evaluated in comparison to regressive autism.

It would be appear that all of this is caused by an immune system gone “haywire”.  I wonder how many other immune dysfunctions leading to regression and odd behaviours will be identified in future decades.

The treatment for all these current, and future, conditions are likely to revolve around immunomodulatory therapy, ranging from very cheap steroids (prednisone) to the very expensive, like IVIG (Intravenous immunoglobulin)

If you have a case of regressive autism and the expert says it does not fit the definition of PANDAS/PANS, he might think the case is closed.  Perhaps it should not be.

I suggest that immune over-activation is involved in both groups of autism:-

Early onset autism

In these cases the immune activation is secondary; when it occurs the existing autism just gets much worse.  In some cases these flare-ups are evidently caused by food allergies/intolerance or pollen allergies.

Regressive Autism

I think that in mild cases, some autism may be solely an over-activation of the immune system, without any of the channelopathies and other dysfunctions common in classic autism.  I would put PANS/PANDAS is this category.  I suggest that many other cases of regressive autism could be traced back to allergies and food intolerance, which triggered an immune over-response.

It does seem that many regressions followed a viral infection, and of course, many people believe their regression was triggered by vaccines.  I expect in most cases the vaccine is just a scapegoat, but I very much doubt it is in every case.   

I do not expect there will be any research in this area, because the results would inevitably be misinterpreted by the public.  What a pity.

If we better understood what events could radically disrupt brain function, we might be able to better understand how to treat the resulting neuropsychiatric phenomena, known as regressive autism, PANDAS, PANS and other, yet to be invented, acronyms.

A serious condition with some serious followers

Many people’s knowledge of autism seems to come from sound bites from scientific luminaries like Oprah, Jenny McCarthy and even Donald Trump.  Somewhat remarkably, the PANS doctors are actually a very serious bunch, under the umbrella of the International OCD Foundation (and the NIMH).  This foundation is a serious organisation with a scientific advisory board loaded with people from top US Medical Schools.

Not only have they concisely explained the symptoms, but they have also found therapies; albeit, they do not really know why they work.

The US National Institute of Mental Health has great information.

There is also a very serious parent run organisation called PANDAS Network.

About PANDAS and PANS

In the early 1990s, 50 years after Kanner noticed autism, researchers in the US noticed what they thought was an odd acute-onset type of Obsessive Compulsive Disorder (OCD).  At first it was thought that only streptococcal infections and Scarlet fever triggered this abrupt regression in the child’s behaviour and cognitive performance.  The first name they came up with was PANDAS, (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections); when reports came in that many other infections caused acute regression the name got changed to PANS (Pediatric Acute-onset Neuropsychiatric Syndrome). 

From Research Subgroup to Clinical Syndrome: Modifyingthe PANDAS Criteria to Describe PANS (Pediatric Acute-onset NeuropsychiatricSyndrome)

Symptoms of PANS

It is pretty clear to me that some people diagnosed with regressive autism actually have PANS.  I have from two sources a list of symptoms:-

International OCD Foundation

• Acute sudden onset of OCD
• Challenges with eating, and at the extreme end, anorexia
• Sensory issues such as sensitivity to clothes, sound, and light
• Handwriting noticeably deteriorates
• Urinary frequency or bedwetting
• Small motor skills deteriorate - a craft project from yesterday is now impossible to complete (see images below)
• Tics
• Inattentive, distractible, unable to focus and has difficulties with memory
• Overnight onset of anxiety or panic attacks over things that were no big deal a few days ago, such as thunderstorms or bugs
• Suddenly unable to separate from their caregiver, or to sleep alone
• Screaming for hours on end
• Fear of germs and other more traditional-looking OCD symptoms

US National Institute of Mental Health

• Severe separation anxiety (e.g., child can't leave parent's side or needs to sleep on floor next to parent's bed, etc.)
• Generalized anxiety. which may progress to episodes of panic and a "terror-stricken look"
• Motoric hyperactivity, abnormal movements, and a sense of restlessness
• Sensory abnormalities, including hyper-sensitivity to light or sounds, distortions of visual perceptions, and occasionally, visual or auditory hallucinations
• Concentration difficulties, and loss of academic abilities, particularly in math and visual-spatial areas
• Increased urinary frequency and a new onset of bed-wetting
• Irritability (sometimes with aggression) and emotional liability. Abrupt onset of depression can also occur, with thoughts about suicide.
• Developmental regression, including temper tantrums, "baby talk" and handwriting deterioration (also related to motor symptoms)

In case you want to see what they mean by regression, look at these pictures drawn by a child with PANDAS before and after treatment.  Panel A is before and Panel B is after.   Source International OCD Foundation

  

Treatment

Compared to Autism, a very refreshing approach is taken to treating PANS.

The treatments include:-

·        Treatment with antibiotics to eradicate the infection, if it is still present.

·        Immune-based therapies such as

o   Plasmapheresis

o   intravenous immunoglobulin (IVIG)

o   corticosteroids (such as prednisone).

The good news about the immune therapies is that the treatment gains were maintained long-term, which is exactly what you would want to see. 

Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood

Implications for Autism

In spite of what your doctor might tell you, if your child has regressive autism, you would be well advised to check and re-check that he/she does not have PANS or a (yet to be identified) variant thereof. 

The immune-based therapies that ultimately are proved to be successful in PANS are highly likely to be helpful in treating the kind of autism in which the immune system remains in a state of over-activation.  Also the immune-therapies being trialled for autism, if successful, might very likely be helpful alternative therapies for PANS; the therapy I have in mind is TSO.

Classic early-onset autism, as researched in post-mortem studies at the Courchesne lab and elsewhere, is associated with physical brain abnormalities, that should be irreversible.  It would seem that PANS is something entirely different and should be treatable and potentially fully recoverable.

For those of you unaware of Courchesne, here is a short video; he is quoted by many of the leading autism researchers, so I hope he has got things right.

Eric Couchesne &Karen Pierce from University of California at San Diego

Where does regressive autism fit in?  I really doubt that all those people with regressive autism have the physical brain abnormalities of classic autism.  Research has shown that regressive autism has even higher bio-markers of neuroinflammation than classic autism.  Perhaps regressive autism is neuroinflammation, without physical brain abnormalities?

Just as PANS is a mini-spectrum of conditions, pathologically distinct from early onset autism, I suspect that regressive autism is equally pathologically distinct from early onset autism.

Why does it matter?  Well if you want to treat something, it helps to know what you are dealing with.

PANS looks like it has some clever people working on it.  Regressive autism, which may indeed be the most prevalent type, is in need of some similarly clever people.

Conclusion

If regressive autism is your area of interest, I would suggest you look very carefully at PANS/PANDAS and the therapies that have been shown to be effective.

If you have PANS/PANDAS, taking a look at the experimental immunomodulatory therapy used in autism might be very worthwhile, for example the TSO therapy from Coronado Bioscience.

We know that PANS/PANDAS is caused by an ongoing inappropriate immune response, but we do not know how this is mediated into the odd behaviours.  One possible mechanism would be via a weakening of the blood brain barrier (BBB).  

It has been shown that the similar mechanism controls the BBB and the gut immune barrier.   Clever research into Celiac Disease has resulted in the discovery of Zonulin, which is now known to be the only physiological modulator of both these barriers.  Using a type of laboratory test called ELISA, it is now possible to measure Zonulin levels.  If people diagnosed with PANS/PANDAS were shown to have low Zonulin levels, we could assume that the BBB was compromised; this would certainly advance understanding of the condition. It would of course point the way to new therapies.

Pregnenolone - an effective OTC anti-inflammatory therapy for autism?

Pregnenolone is the true mother hormone, being derived from cholesterol and the precursor of all steroid hormones. 

It is a potent anti-inflammatory agent.  It is  also claimed that supplementing with Pregnenolone will increase IGF-1, which I found interesting, given my very recent post on IGF-1 therapy in autism.  

In the late 1940’s and 1950’s successful studies were carried out into the use of Pregnenolone in the inflammatory condition of arthritis. 

As we found in recent posts regarding the vagus nerve, all inflammatory conditions (autism included) share much in common.  A treatment that is effective against neuroinflammation in one condition should be tested in the others.

Interest was high in Pregnenolone because it was cheap and free of troubling side effects.  Alternative steroid treatments, for example with Prednisone, can have major side effects.

In an earlier post I referred to the successful use of the steroid Prednisone in ASD in the US.  Wider adoption, and the lack of clinical trials, are held back by the fear of side effects.

Promoting Speech in a 7 year old Non-verbal Child with Autism

"... Dr Michael Chez, of the Pediatric Neurology and Autism Neurodevelopmental Program, Sutter Neuroscience Institute in Sacramento California.  He wrote a paper I have already referred to in this blog called:-

Immune Therapy in Autism: Historical Experience and Future Directions with Immunomodulatory Therapy

In that paper he talks of his knowledge of the effects of prednisone on children with autism and he mentions the dosage used.

Treatment was usually prescribed with daily prednisone doses of 2 mg/kg/day for 3 to 6 months. Limitations to therapy were usually Cushingoid side effects. As in other chronic conditions requiring steroids, pulse dosing was tried with steroids in the form of prednisone or prednisolone at 5 to 10 mg/kg twice per week.

Long-term success with no dependence or minimal Cushingoid effects has been noted in several hundred patients treated in this manner (Chez, unpublished data, personal communication).

In all, 17 of 32 patients showed response to prednisone after 2 to 4 months of treatment (53%). Improvements were seen on EEG and in language skills of the patients. Other steroid treatment series of regressed language in autistic spectrum patients diagnosed with LKS variant showed improved language with pulse-dose steroids."

 Pregnenolone Studies

Pregnenolone in the Treatment of Rheumatoid Arthritis

Pregnenolone in Rheumatoid Arthritis

If effect, Pregnenolone seems to be a weaker, but much safer, alternative to Prednisone.  Some people with arthritis currently take it. 

Pregnenolone is indeed already one of hundreds of fringe treatments for autism.  There are some very good reasons why it should be effective. 

Stanford University are currently running a clinical trial of Pregnenolone on adults with autism. It is the same researcher that worked on their study on NAC in children with autism.  It is nice to know that the adults with ASD have not been forgotten; after all, children have a habit of growing up.

A Study of Pregnenolone in the Treatment of Individuals With Autism

Conclusion

The next time I receive a question on this blog asking for a potentially effective OTC anti-neuroinflammatory “supplement” for autism, I will know what to suggest trying.

Promoting Speech in a 7 year old Non-verbal Child with Autism

I was recently asked if I would be happy to talk to the parents of a 7 year old non-verbal child with autism.  I agreed to share what I have learned so far from both behavioural interventions and more recently from drug therapy.  I decided that a dedicated post could also be very useful.

When Monty, now aged 10, was diagnosed with autism aged three and a half, he embarked on a home-based ABA programme, soon complemented by the use of PECS (Picture Exchange Communication System).  PECS is great, and when correctly implemented, clearly can work wonders.  Sadly, most people take shortcuts and just laminate a few pictures, stick them on the fridge and say they are “doing PECS”.

Click below to see short training videos:-

Phase 1 PECS

Phase 2 PECS

 

Once a non-verbal child has a communication system, be it PECS or sign language, then he/she can open up to the world.  Often speech then follows, but not always.

Monty learned to talk using ABA, PECS and special computer software.

With what I have since learned about the possibility of safe and effective drug therapy, I would do things slightly differently.  I would keep all the ABA and PECS and just add Bumetanide, NAC and Atorvastatin.  I can never know if Monty would have then spoken earlier, but I am pretty sure that would have been the effect.

 

Science based, not “Biomedical”, not Complimentary Medicine and not DAN!

Just in case you are wondering, my findings are based on reading the scientific literature on autism and its comorbidities.  I decide what research looks sound and what looks dubious; I draw my own conclusions.  “Biomedical” is a word that has been hijacked to apply to therapies that we would like to work, but usually lack a thorough grounding in science.  DAN seems to stand for trying everything, “Biomedical” and more.  Nonetheless, within the hundreds of DAN therapies are at least one or two that do stand up to scientific investigation.  

By applying a very blinkered view to the existing research, the Medical Establishment’s general view continues to be that autism is pretty much untreatable.  Having accepted this view myself for several years, I have learned that this view is fundamentally flawed; you just have to objectively follow the science and do a little research yourself.

 

7 years old and non-verbal

The longer a child remains non-verbal, the more challenging it becomes.  After a long period of time a child will just not see the point of changing.  It may cease to be a biological problem and become just a behavioural problem.

My combination of Bumetanide, NAC and Atorvastatin is as close as you can ever get with drugs to being risk free.  This has been a prerequisite of mine.  If after 7 years my child was non-verbal, I would probably be willing to take additional risks, but still nothing without clearly understood boundaries.

For the last few years we have had a little box in our kitchen drug cabinet marked “emergency asthma drug, one a half tablets”.  We have never had to actually use this drug.  The drug is Prednisone and it is for use when an acute asthma attack does not respond to the Ventolin “rescue” inhaler.  Prednisone is a corticosteroid, widely available, cheap and saves lives; but long term use can have major side effects. 

Prednisone lowers the body's immune system.  The science suggests that the overactive/damaged immune system in autism is a factor behind the autistic behaviours in children with ASD.  It would seem logical that temporarily lowering the immune system might trigger behavioral change in autsim, such as regaining lost speech or initiating it.  The most serious doctor I could find who is knowledgeable about this subject is Dr Michael Chez, of the Pediatric Neurology and Autism Neurodevelopmental Program, Sutter Neuroscience Institute in Sacramento California.

 

He wrote a paper I have already referred to in this blog called:-

Immune Therapy in Autism: Historical Experience and Future Directions with Immunomodulatory Therapy

In that paper he talks of his knowledge of the effects of prednisone on children with autism and he mentions the dosage used.

. Treatment was usually prescribed with daily prednisone doses of 2 mg/kg/day for 3 to 6 months. Limitations to therapy were usually Cushingoid side effects. As in other chronic conditions requiring steroids, pulse dosing was tried with steroids in the form of prednisone or prednisolone at 5 to 10 mg/kg twice per week.  

Long-term success with no dependence or minimal Cushingoid effects has been noted in several hundred patients treated in this manner (Chez, unpublished data, personal communication).

In all, 17 of 32 patients showed response to prednisone after 2 to 4 months of  treatment (53%). Improvements were seen on EEG and  in language skills of the patients. Other steroid treatment series of regressed language in autistic spectrum patients diagnosed with LKS variant showed improved language with pulse-dose steroids.

Going to California is not an option for most people, but if I had a 7 year old non-verbal child with autism and ABA/PECS did not help initiate speech, then I would certainly read up on what he is suggesting.  I would still focus the time and effort on ABA/PECS and just hope that the drugs provide a little extra push.





 

Asthma-Autism Hypothesis and Immunomodulatory Therapy for Autism

You may be aware that about a third of people with autism also have asthma; this is not a coincidence, just as the finding that autistic people have elevated cholesterol was not a coincidence. 

Since Monty, aged 10,  has both autism and asthma, I have had to become informed on both conditions.  Having now read the research on both autism and asthma, it is somewhat shocking that there are so  many parallels.  I would now go so far as to make my own hypothesis:-

The causes of Autism and Asthma are overlapping; so much so, that some drug treatments for the core symptoms of one may be effective in the other.

This may sound a strange, even bizarre proposition, but I will show that it is at worst plausible and at best proven.  Note that it was the observation that bumetanide was an effective treatment in neonatal non-convulsive seizures ,that led to the idea of trialling that drug on autistic children.  Many children with autism subsequently develop epilepsy or other forms of seizure.  So investigating the so-called comorbidities is not such a novel idea.
 

Drugs effective in both Asthma & Autism

·         NAC (N-acetyl cysteine) – reduces oxidative stress

·         Prednisone – powerful steroid for short term use to supress immune system

·         Statins – reduce neuroinflammation

·         Ketotifen – mast cell stabilizer and anti-histamine

In case you are not familiar with asthma, there are some remarkable similarities between asthma and autism, just take a look:-

·         Both affects boys much more than girls

·         Both involve neuroinflammation

·         Both are linked to defects in the auto-immune system

·         Exact cause of both is not known, but is seen as a combination of genetic and environmental factors

·         Both were thought of as a psychological disorders and were unsuccessfully treated as such

·         Both are usually lifelong conditions, though functional recovery is much more common with asthma than autism, often occurring after puberty with asthma

·         In recent decades there has been an “epidemic” increase in prevalence of both. 

Asthma is much more prevalent among those with autism the general population and is frequently cited as a comorbidity, along with epilepsy and GI disorders.

Left untreated, asthma can easily be fatal, so it has been well studied and numerous drugs have been specially developed.  I thought that perhaps there are insights for autism to be gained by looking at how asthma is treated;   indeed there are.

Asthma Prevalence

There is a lot of research into the prevalence of asthma.  After increasing for several decades, there are some reports of it plateauing or even declining.

Is the prevalence of asthma declining? Systematic review of epidemiological studies

 

It is generally accepted that asthma is a disease of the developed world and the apparently the English-speaking world in particular.

Asthma Statistics

The American Academy of Allergy Asthma & Immunology (AAAAI) has an eye-opening summary of asthma statistics showing:-

·         The prevalence of asthma in different countries varies widely, but the disparity is narrowing due to rising prevalence in low and middle income countries and plateauing in high income countries.

·         An estimated 300 million people worldwide suffer from asthma, with 250,000 annual deaths attributed to the disease.

·         It is estimated that the number of people with asthma will grow by more than 100 million by 2025.

·         Workplace conditions, such as exposure to fumes, gases or dust, are responsible for 11% of asthma cases worldwide.

·          About 70% of asthmatics also have allergies.

·         Approximately 250,000 people die prematurely each year from asthma. Almost all of these deaths are avoidable.

·         Occupational asthma contributes significantly to the global burden of asthma, since the condition accounts for approximately 15% of asthma amongst adults.
 

Asthma Treatment

To learn more about asthma and how it is treated the University of Maryland have a helpful summary, just click the link.

There are generally three lines of treatment.  The well-known first line of treatment is the “rescue” inhaler that children are seen with at school, this is to treat acute attacks.  These are bronchodilators, like Ventolin, that open the airways in moderate to severe attacks.

If acute attacks become frequent, then typically an anti-inflammatory steroid inhaler is prescribed.  Long-term control medications are essential to minimize long-term damage of the inflammatory response, to reduce the risk of serious exacerbations.  This is used daily in the hope of preventing future attacks.

In case of an acute attack that does not respond to the rescue inhaler, an oral corticosteroid can be given .  These are powerful drugs that because they are administered orally will affect the whole body;  the steroid inhaler substantially avoids this drawback.  The corticosteroid  works by deactivating the immune system.
 

There are many other therapies used by allergists, in particular the use mast cell stabilizers and anti-histamine drugs.

Ketotifen

Ketotifen is mast cell stabilizer, which means it blocks mast cells from releasing histamine it is also an H1 antagonist, which means it blocks H1 histamine receptors.  It is primarily used as a long term treatment of asthma.  It will not stop an acute asthma attack, but it should reduce their frequency.  If given to high risk children, its use can avoid the initial onset of asthma.

Prevention of asthma by Ketotifenin infants with atopic dermatitis.

It is used in irritable bowel syndrome and it is by DAN doctors to treat GI problems in autism.  If have read about mast cells and Dr Theoharides, then you can see how mast cells may play a key role in autistic behaviour and as such Ketotifen could be a prime therapy.

Autism and the auto immune system

There is a substantial body of opinion that autism is itself a disease linked to the auto immune system, like asthma and indeed type 1 diabetes.  The over active immune system is destroying certain important body functions.

The logical conclusion would be to find a way to down rate the immune system so that the unwanted affects were minimized, without leaving the body open to attack.  This strategy is indeed followed in asthma therapy where the emergency treatment is oral corticosteroid Prednisone

If all this sounds familiar, it should do.  The hygiene hypothesis has also been used to  link asthma, autism and the overactive immune response. 

In the case of autism at least one therapy is also based on this approach.

There is the case of Stewart Johnson in America, who trawled through the research looking for ways to help his autistic son.  He became convinced that the immune system was the key and looked into ways to down rate it.  He came upon the idea of using the TSO parasitic worms.  These parasites live in pigs(?) and in order to preserve themselves they evolved a method of reducing the immune system of their host so that they would not be expelled.  Treatment with such worms has been tried with other conditions, such as Crohn’s disease.  Mr Johnson ordered some TSO from Germany and fed them to his son.  He found that initially there was no impact on his son’s autism, but when he increased the dose there was a marked reduction in autistic behaviours.

Every couple of weeks or so, he gave his son another dose of TSO.

A clinical trial is being carried out at the Albert Einstein medical school to test the effectiveness of the treatment.  Mr Johnson created a website to document his experiences.  

It appears that not all people with autism respond to TSO; perhaps this is not surprising, not all people with autism have asthma either.

Perhaps Mr Johnson should see if a mild dose of Prednisone has the same effect as the worms?

Prednisone & Autism

It turns out that some doctors have indeed been prescribing prednisone for autism.  Most are DAN doctors, but not all.

You will even see on autism forums that when kids were given prednisone for their asthma, they suddenly had a big improvement in their autism.

http://www.autismweb.com/forum/viewtopic.php?p=109879

http://www.autismweb.com/forum/viewtopic.php?f=4&t=30238

While extended use of steroids causes side effects, it seems some doctors used them to try to proactively reverse regressive autism and to get non-verbal kids to speak.  This would seem entirely logical.

Immunomodulatory Therapy in Autism

An truly excellent review paper of Immunotherapy in Autism has been written by Dr Michael Chez, a respected mainstream specialist from Sacramento.  He also seems to be endorsing the use of the prednisone steroid in autism therapy

Immune Therapy in Autism: Historical Experience and Future Directions with immunomodulatory Therapy

 Here are two important paragraphs:-

Experience with EEG abnormalities and autistic regression cases that respond to steroids have been described in various case reports. Treatment was usually prescribed with daily prednisone doses of 2 mg/kg/day for 3 to 6 months. Limitations to therapy were usually Cushingoid side effects. As in other chronic conditions requiring steroids, pulse dosing was tried with steroids in the form of prednisone or prednisolone at 5 to 10 mg/kg twice per week. Long-term success with no dependence or minimal Cushingoid effects has been noted in several hundred patients treated in this manner.

 

In summary, among the current studies of immune targeted therapies, the most collective data on steroid effects on autism is probably the largest. Clear clinical improvements are consistent between different groups that had peer-reviewed assessments. In addition, all reported similar outcomes and side effects were made with the use of steroids. As in IVIG treatment, there has been no report of cure or elimination of all autism features. In the majority of cases, steroid effects did not permanently alter an autism diagnosis in these patients. Clinical concerns about steroid dependency and side effects, such as Cushingoid or long-term, well-known steroid effects have limited more randomized or controlled studies of steroid medications in autism. This is unfortunate, as there may be a potential for significant improvement from steroid treatment on cytokine and chronic immune dysregulation in autism.

Oxidative Stress, Nitrative Stress and Inflammation in Asthma

Much has been written about oxidative stress and inflammation in autism, well it turns out these are key issues in asthma.  In asthma, fortunately, they have been looked into very seriously and all is well documented.

Another superb paper, this time by Professor Peter Barnes, from Imperial College in London is:- 

Histone acetylation and deacetylation: importance in inflammatory lung diseases

 This paper should be read from cover to cover, it is full of interesting information.  For example cigarette smoking in asthma causes oxidative stress.  That stress continues even after the patient has given up smoking, so it is chronic.  To treat this oxidative stress, guess what? He uses NAC just like I using for oxidative stress in my son’s autism.

Also, oxidative Stress causes steroid resistance, so steroids that work in asthma do not work well in COPD.

Cytokines in asthma

Because asthma affects so many people and can be fatal, there is a considerable research effort and drug pipeline.

Cytokines play a key role in all inflammation.  The keys ones have been identified in both autism and asthma; the difference is that in asthma they are being studied in great detail.

Also several cytokine modulators are in various stages of development, but tested on asthma sufferers.
 

For the scientists among you, this subject is covered in depth by Professor Barnes, from Imperial College.

The cytokine network in asthma and chronic obstructive pulmonary disease

How Corticosteroids control inflammation

If you are tempted to make a trial of Prednisone, then you should be interested a read how such steroids control inflammation.  Here is an excellent paper that explains how corticosteroids control inflammation:-

How corticosteroids control inflammation: Quintiles Prize Lecture 2005

 

Asthma and statins 

I have established that the anti-inflammatory properties of statins, already applied neuroscientists in other fields, are very helpful in treating autism.

Researchers are also looking to see whether these properties of statins can be helpful in treating asthma.  Here is a recent paper:-

Do statins improve outcomes in patients with asthma on inhaled corticosteroid therapy? A retrospective cohort analysis

The paper concludes -

The findings suggest beneficial effects of statins in asthma management.

 Yet again the same drug has a positive effect in both conditions.

Conclusion

If you have made it this far in my post, congratulations!

So far from asthma, the autism world has taken Prednisone, Ketotifen and NAC.  I suspect that as new anti-inflammatory drugs are developed for asthma, other little gems will become available.  Also new stronger anti-oxidants are likley to be developed for asthma, since they find NAC not powerful enough. 

Prednisone clearly has drawbacks, but in the case of a sudden regression in autism, it might well be a very smart short term intervention.  Perhaps also in kick-starting development where it has stalled/plateaued.

Quite remarkably, statins not only reduce autistic behaviours but also help control asthma.

I think I have proved my hypothesis

The causes of Autism and Asthma are overlapping, so much so, that some drug treatments for the core symptoms of one may be effective in the other.

Also, we learned from Professor Barnes that corticosteroids do not work well in the presence of oxidative stress.  In asthma he reduces this stress using NAC; I do the same in autism with NAC.  This means that if you are going to trial prednisone, it would be very wise to start with NAC first.  It also means that if your child has both autism and asthma, their inhaled steroid will work better if you  are also using both NAC and statins.   

In case you were wondering, prednisone, Ketotifen and statins are all off-patent and very cheap.  NAC is an OTC supplement and inexpensive if you buy it online.