Showing posts with label IVIG. Show all posts
Showing posts with label IVIG. Show all posts

Wednesday 8 July 2020

Immune modulatory treatments for autism spectrum disorder

Need a wizard, or your local doctor?

I was intrigued to come across a recent paper on immune modulatory treatments for autism by a couple of doctors from Massachusetts General Hospital for Children.  The lead author has interests in:

·      Autism spectrum disorders
·      Psychopharmacology
·      Developmental Disabilities
·      Williams syndrome
·      Angelman syndrome
·      Down syndrome

Apparently, he is an internationally-recognized expert in the neurobiology and neuropsychopharmacology of childhood-onset neuropsychiatric disorders including autistic disorder.  Sounds promising, hopefully we will learn something new.

The paper is actually a review of existing drugs, with immunomodulatory properties, that have already been suggested to be repurposed for autism. The abstract was not very insightful, so I have highlighted the final conclusions and listed the drugs, by category, that they thought should be investigated further.

All the drugs have already been covered in this blog and have already been researched in autism.

One important point raised in the conclusion relates to when the drugs are used.  Autism is a progressive condition early in life and there are so-called “critical periods” when the developing brain is highly vulnerable.

For example, Pentoxifylline has been found to be most effective in very young children.  This does not mean do not give it to a teenager with autism, it just means the sooner you treat autism the better the result will be.  This is entirely logical.

Some very clever drugs clearly do not work if given too late, for example Rapamycin analogs used in people with TSC-type autism.

Multiple Critical Periods for Rapamycin Treatment to Correct Structural Defects in Tsc-1-Suppressed Brain

Importantly, each of these developmental abnormalities that are caused by enhanced mTOR pathway has a specific window of opportunity to respond to rapamycin. Namely, dyslamination must be corrected during neurogenesis, and postnatal rapamycin treatment will not correct the cortical malformation. Similarly, exuberant branching of basal dendrites is rectifiable only during the first 2 weeks postnatally while an increase in spine density responds to rapamycin treatment thereafter.  

Back to today’s paper.

The identification of immune dysregulation in at least a subtype ASD has led to the hypothesis that immune modulatory treatments may be effective in treating the core and associated symptoms of ASD. In this article, we discussed how currently FDA-approved medications for ASD have immune modulatory properties.

“Risperidone also inhibited the expression of inflammatory signaling proteins, myelin basic protein isoform 3 (MBP1) and mitogen-activated kinase 1 (MAPK1), in a rat model of MIA. Similarly, aripiprazole has been demonstrated to inhibit expression of IL-6 and TNF-α in cultured primary human peripheral blood mononuclear cells from healthy adult donors.”

We then described emerging treatments for ASD which have been repurposed from nonpsychiatric fields of medicine including metabolic disease, infectious disease, gastroenterology, neurology, and regenerative medicine, all with immune modulatory potential. Although immune modulatory treatments are not currently the standard of care for ASD, remain experimental, and require further research to demonstrate clear safety, tolerability, and efficacy, the early positive results described above warrant further research in the context of IRB-approved clinical trials. Future research is needed to determine whether immune modulatory treatments will affect underlying pathophysiological processes affecting both the behavioral symptoms and the common immune-mediated medical co-morbidities of ASD. Identification of neuroimaging or inflammatory biomarkers that respond to immune modulatory treatment and correlate with treatment response would further support the hypothesis of an immune-mediated subtype of ASD and aid in measuring response to immune modulatory treatments. In addition, it will be important to determine if particular immune modulating treatments are best tolerated and most effective when administered at specific developmental time points across the lifespan of individuals with ASD.

Here are the drugs they listed:-

1.     Metabolic disease


Spironolactone is a cheap potassium sparing diuretic. It has secondary effects that include reducing the level of male hormones and some inflammatory cytokines.

Pioglitazone is drug for type 2 diabetes that improves insulin sensitivity.  It reduces certain inflammatory cytokines making it both an autism therapy and indeed a suggested Covid-19 therapy.

Pentoxifylline is a non-selective phosphodiesterase (PDEinhibitor, used to treat muscle pain.  PDE inhibitors are very interesting drugs with a great therapeutic potential for the treatment of immune-mediated and inflammatory diseases.  Roflumilast and Ibudilast are PDE4 inhibitors that also may improve some autism.  The limiting side effect can be nausea/vomiting, which can happen with non-selective PDE4 inhibitors.

I did try Spironolactone once; it did not seem to have any effect.  It is a good match for bumetanide because it increases potassium levels.

I do think that Pioglitazone has a helpful effect and there will be another post on that.

PDE inhibitors are used by readers of this blog. Maja is a fan of Pentoxifylline, without any side effects. Roflumilast at a low dose is supposed to raise IQ, but still makes some people want to vomit. The Japanese drug Ibudilast works for some, but nausea is listed as a possible side effect.

2.     Infectious disease


Minocycline is an antibiotic that crosses in to the brain.  It is known to stabilize activated microglia, the brain’s immune cells.  It is also known that tetracycline antibiotics are immunomodulatory.

Vancomycin is an antibiotic used to treat bacterial infections, if taken orally it does not go beyond the gut.  It will reduce the level of certain harmful bacteria including Clostridium difficile.

Suramin is an anti-parasite drug that Dr Naviaux is repurposing for autism, based on his theory of cell danger response.

3.     Neurology

Valproic acid

Valproic acid is an anti-epileptic drug.  It also has immunomodulatory and HDAC effects, these effects can both cause autism when taken by a pregnant mother and also improve autism in some people.

Valproic acid can have side effects. Low dose valproic acid seems to work for some people. 

4.     Gastroenterology

Fecal microbiota transplant (FMT)

FMT is currently used to treat recurrent Clostridium difficile infection and may also be of benefit for other GI conditions including IBD, obesity, metabolic syndrome, and functional GI disorders.

Altered gut bacteria (dysbiosis) is a feature of some autism which then impairs brain function.  Reversing the dysbiosis with FMT improves brain function.  

5.     Oncology

Lenalidomide is an expensive anti-cancer drug that also has immunomodulatory effects.

Romidepsin is a potent HDAC inhibitor, making it a useful cancer therapy.  HDAC inhibitors are potential autism drugs, but only if given early enough not to miss the critical periods of brain development. 

6.     Pulmonology


Many people with autism respond well to NAC. You do need a lot of it, because it has a short half-life.

7.     Nutritional medicine and dietary supplements

Omega-3 fatty acids
Vitamin D

Nutritional supplements can get very expensive.  In hot climates, like Egypt, some dark skinned people cover up and then lack vitamin D.  A lack of vitamin D will make autism worse.

Some people with mild brain disorders do seem to benefit from some omega-3 therapies.

Flavonoids are very good for general health, but seem to lack potency for treating brain disorders.  Quercetin and luteolin do have some benefits. 

8.     Rheumatology

Intravenous immunoglobulin (IVIG)

Celecoxib is a common NSAID that is particularly well tolerated (it affects COX-2 and only marginally COX-1, hence its reduced GI side effects).

NSAIDS are used by many people with autism.

Steroids do improve some people’s autism, but are unsuitable for long term use.  A short course of steroids reduces Covid-19 deaths – a very cost effective therapy.

IVIG is extremely expensive, but it does provide a benefit in some cases. IVIG is used quite often to treat autism in the US, but rarely elsewhere other than for PANS/PANDAS that might occur with autism.

9.     Regenerative medicine

Stem cell therapy

I was surprised they gave stem cell therapy a mention. I think it is still early days for stem cell therapy.


I have observed the ongoing Covid-19 situation with interest and in particular what use has been made of the scientific literature.

There are all sorts of interesting snippets of data. You do not want to be deficient in Zinc or vitamin D, having high cholesterol will make it easier for the virus to enter your cells.  Potassium levels may plummet and blood becomes sticky, so may form dangerous clots. A long list of drugs may be at least partially effective, meaning they speed up recovery and reduce death rates. Polytherapy, meaning taking multiple drugs, is likely to be the best choice for Covid-19.

Potential side effects of some drugs have been grossly exaggerated, as with drugs repurposed for autism.  Even in published research, people cheat and falsify the data. In the case of hydroxychloroquine, the falsified papers were quickly retracted.

The media twist the facts, to suit their narrative, as with autism.  This happens even with Covid-19. Anti-Trump media (CNN, BBC etc) is automatically anti-hydroxychloroquine, and ignores all the published research and the results achieved in countries that widely use it (small countries like China and India). 

Shutting down entire economies when only 5-10% of the population have been infected and hopefully got some immunity, does not look so smart if you are then going to reopen and let young people loose.  They will inevitably catch the virus and then infect everyone else. Permanent lockdown restrictions, if followed by everyone, until a vaccine which everyone actually agreed to take, makes sense and living with the virus makes sense, but anything in between is not going to work. After 3 months without any broad lockdown, and allowing young people to socialize, most people would have had the virus and then those people choosing to shield could safely reemerge. The death rate with the current optimal, inexpensive treatment, as used in India or South Africa is very low, in people who are not frail to start with. Time to make a choice.  Poor people in poor countries cannot afford to keep going into lockdown, they need to eat.

What hope is there for treating a highly heterogeneous condition like autism, if it is not approached entirely rationally and without preconceptions and preconditions?  In a pandemic we see that science does not drive policy and translating science into therapy is highly variable.  The science is there for those who choose to read it.

I frequently see comments from parents who have seen some of the research showing that autism has an inflammatory/auto-immune component.  They ask why this has not been followed up on in the research.  It has been followed up on.  It just has not been acted upon.

Why has it not been acted on?

This missing stage is called “translation”.  Why don’t doctors translate scientific findings into therapy for their patients?

What is common sense to some, is “experimental” to others. “Experimental” is frowned upon in modern medicine, but innovation requires experimentation.

Many people’s severe autism is unique and experimental polytherapy/polypharmacy is their only hope.

The cookie cutter approach is not going to work for autism. 

Thankfully, for many common diseases the cookie cutter approach works just fine.

Do the authors of today’s paper, Dr McDougle and Dr Thom, actually prescribe to their young patients many of the drugs that they have written about?  I doubt it and therein lies the problem.  

Time for that wizard, perhaps? 

A few years ago I did add the following tag line, under the big Epiphany at the top of the page. 

An Alternative Reality for Classic Autism - Based on Today's Science

You can choose a different Autism reality, if you do not like your current one.  I am glad I did. I didn't even need a wizard.  

There are many immuno-modulatory therapies for autism that the Massachusetts doctor duo did not mention, but it is good that they made a start.

Friday 10 July 2015

Clinical Investigation vs Off-Label Treatment for Autism

Antonio Hardan, the psychiatrist at the Stanford School of Medicine, has published another paper.  Hardan is interesting, he is a clinician rather than a rocket scientist, but he gets involved in a very wide variety of clinical trials, usually of existing drugs that might be effective in autism.

In his latest paper, this time about Glutamatergic Dysfunction in Autism, he highlights the problems with clinical trials:-

·        Heterogeneity of autism

·        Subjective rating scales rather than biological measures.

In other words there is no single autism and there is no good way to reliably measure the efficacy of any drug tested on it.  Consider what that really means.

Hardan really should know about this, just look at the clinical trials he has been involved in:-

So why bother with Clinical Trials?

This may sound like a very unscientific question, but perhaps it is not.  A couple of years ago Roche pulled the plug on Arbaclofen, because it “failed” in its autism clinical trial.  Many parents thought it worked.  Now the Simons Foundation has acquired the rights to the drug and is restarting trials.  How many other trial drugs were prematurely brushed aside?

Many years ago the hormone secretin was put forward as a therapy for autism, particularly for people with GI problems.  Several expensive clinical trials later, it was determined to be ineffective.  But some people continued to rave about it.  Where they all deluded?

The very expensive IVIG therapy has also been put forward as a wonder therapy for autism.  The critics highlight that in studies 90% of people do not benefit and therefore the therapy has little value.  But what if you are in 10% that do respond very well?

Intravenous immunoglobulin treatment of children with autism.


Since autism has been associated with immunologic abnormalities suggesting an autoimmune cause of autistic symptoms in a subset of patients, this study was undertaken to investigate whether intravenous immunoglobulin (i.v.Ig) would improve autistic symptoms. Ten autistic children with immunologic abnormalities, demonstrated on blood tests, were enrolled in this study. Their ages ranged from 4 to 17 years, with two girls and eight boys. Eight children (1 female and 7 male) historically had undergone autistic regression. Intravenous immunoglobulin, 200 to 400 mg/kg, was administered every 6 weeks for an intended treatment program of four infusions. In five children, there was no detectable change in behavior during the treatment program. In four children, there was a mild improvement noted in attention span and hyperactivity. In none of these children did the parents feel that the improvement was sufficient to warrant further continuation of the infusions beyond the termination of the program. Only in one child was there a very significant improvement, with almost total amelioration of autistic symptoms over the time period of the four infusions. Once the treatment program was completed, this child gradually deteriorated over a 5-month time period and fully reverted to his previous autistic state. In this treatment program, five children had no response to intravenous immunoglobulin. In the four children who showed mild improvements, those improvements may simply have been due to nonspecific effects of physician intervention and parental expectation (ie, placebo effect). However, in one child there was a very significant amelioration of autistic symptoms. There were no distinguishing historic or laboratory features in this child who improved. Given a positive response rate of only 10% in this study, along with the high economic costs of the immunologic evaluations and the intravenous immunoglobulin treatments, the use of intravenous immunoglobulin to treat autistic children should be undertaken only with great caution, and only under formal research protocols.

Just in this blog, which is amateur and not intended as a rigorous scientific review, we have seen numerous “rare” conditions that lead to “autism” that are actually treatable.

If you add up all these “rare” conditions you get a sizeable proportion of all the autism, diagnosed in those under four years old (i.e. more severe autism).

Clinical Investigations

If you accept that the initial autism diagnosis really tells very little, then you are left, like Hardan, testing all sorts of clever ideas on a trial group of kids who may have one to several, of thousands of discrete dysfunctions (CNVs etc.).

Then if you get a 10% response rate, you are doing great.

If you target something like oxidative stress, that is caused by hundreds of those thousands of discrete dysfunctions (CNVs etc.), then your odds of success shoot up.  This was the case in Hardan’s trial of N-acetyl cysteine.

Hardan is now going to trial oxytocin on kids with autism, but this idea has already been well and truly “trashed” by highly respected mainstream doctors.  They do this because they think autism is something easy to define and measure like high blood pressure.  If it is therapeutic in 10% of cases, that is great.

Quacks, Off-label and Clinical Investigations

I think it is great that Hardan can try all these drugs at Stanford and nobody even thinks of calling him a quack.  The same applies to a small number of inquisitive doctors at Johns Hopkins and Boston Children’s Hospital.

It would be interesting to know how Hardan treats his patients with ASD, who are not enrolled in a clinical trial.  Does he prescribe off-label? 

It is clear that most doctors in developed countries will run a mile/kilometer at the idea of treating somebody off label.  They fear being struck off/sued/ridiculed.

We had the UK pediatrician commenting on this blog that Baclofen was effective in 70+% of her/his patients with anxiety plus Asperger’s, but did not feel happy to continue prescribing it without some supporting evidence from elsewhere.  The fact that it was safe and effective was not enough.

Many of the tiny number of off-label doctors really do look like quacks to me, so I can understand the concern of mainstream doctors not to want to be associated with them.

What is the, scientifically well-briefed, parent supposed to do? (if self-treating is not an option)

I think there should be a way where you can enroll your child in a “clinical investigation”, where you accept that all the treatments are experimental and therefore have a higher level of risk than normal.  You waive your right to sue the doctor, or the hospital.  You can opt out of up to 10% of the therapies, based on valid concern.  For example, you might think IVIG is not safe.

You then enter a program in which all your child’s data can be used for research purposes.  So you agree to have to have EEGs, scans, genetic testing, spinal tap/lumbar puncture, blood tests, urine tests, hair tests etc.

The child is completely profiled and material is stored for possible further analysis later.

All known tests are then carried out, even obscure things like biotin deficiency, creatine deficiency and those amino acids we saw that triggered rare autism.

Then you go through all of the therapies known to be effective in some people.  So it includes memantine, IVIG,  donepezil, bumetanide, oxytocin, propranolol, baclofen, arbaclofen, even Zyrtec, NAC, D-Cycloserine, carnosine, carnitine, pancreatic enzymes, probiotic bacteria  etc.

The whole process would take a year.  If you treated 1,000 children you would then have a wealth of data.

You might have individually rare disorders totaling 15% of cases and then several clusters where the same drugs were effective in sizeable groups of children.  Then you would be able to look back in the data for the biomarkers of each cluster.

Then you would write a smartphone app for doctors to treat autism.  They would input the various biomarkers requested and out would come the suggested drug therapy recommendation(s).  So it would be a “guided off-label” approach where the doctor knows that the recommendations are “scientifically supported” but may not be perfect.

We just need the Simons Foundation to sponsor it! 

If you think it might be too expensive, just remember that at the recent international autism conference in Utah, there were 2,000 scientists and researchers in attendance. What exactly have they achieved, in practical terms, in the last 10 years and are likely to achieve in the next 10 years?

It does seem that some view success as diagnosing ever more people with "autism", so that they can receive "services", when they really should be diagnosing specific biological dysfunctions.

It is not an easy task, but you do not need 2,000 researchers.  You just need 20 pragmatic people to review the data and make a decision tree showing how to choose the 5 drugs most likely to help a particular person, based on their specific biomarkers.  

I guess that would leave 1,980 people with not much to do. 

Saturday 21 June 2014

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.


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.


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). 

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


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   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.

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.


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.