Immunomodulatory Therapy in Autism - Potassium Channel Kv1.3, Parasitic Worms, and their ShK–related peptides

Regular readers of this post will know that I believe that Immunomodulatory therapy has great promise for treating various subtypes of autism.  In effect, I want to bring the over-activated immune system back under control.  Two methods that appeal are:-

·        The steroid, Prednisone, because it is cheap and though it has side effects, they are very well understood. It also has been shown to be effective in autism and related conditions like PANDAS and Landau-Kleffner syndrome (LKS)

·        Parasitic worms appeal because they are known to have beneficial effect in many auto-immune conditions ranging from arthritis to autism, but nobody really understood why.  Until now.

This post is about the worms and recent research which has established that it is likely that they work by blocking the potassium channel Kv1.3.

You will have noted that this blog keeps going on about ion channel dysfunctions and autism.  We already know that Cl^-, Ca²⁺ , K⁺ and Na²⁺ are all implicated.

When researching calcium channel blockers for autism, one reason I picked Verapamil was that it is also a potassium channel blocker.  My earlier experiments have shown that hypokalemic sensory overload exists in autism, I showed that oral potassium could treat sensory overload.

Hypokalemic Autistic Sensory Overload

 

This blog is (slowly) working its way through the ion channel dysfunctions known to exist in autism.

Well, it appears that Verapamil also blocks Kv1.3.

Block of the lymphocyte K+ channel mKv1.3 by the phenylalkylamine verapamil

Research Down Under

Researchers in Australia have identified the chemicals released by parasitic worms that have the effect of subduing the immune system.  They identified a large family of Stichodactyla helianthus toxin (ShK)–related peptides in parasitic worms, they showed that these peptides acted to inhibit Kv1.3 channels in human T cells.

Kv1.3 channel-blocking immunomodulatory peptides from parasitic worms: implications for autoimmune diseases

Abstract

The voltage-gated potassium (Kv) 1.3 channel is widely regarded as a therapeutic target for immunomodulation in autoimmune diseases. ShK-186, a selective inhibitor of Kv1.3 channels, ameliorates autoimmune diseases in rodent models, and human phase 1 trials of this agent in healthy volunteers have been completed. In this study, we identified and characterized a large family of Stichodactyla helianthus toxin (ShK)–related peptides in parasitic worms. Based on phylogenetic analysis, 2 worm peptides were selected for study: AcK1, a 51-residue peptide expressed in the anterior secretory glands of the dog-infecting hookworm Ancylostoma caninum and the human-infecting hookworm Ancylostoma ceylanicum, and BmK1, the C-terminal domain of a metalloprotease from the filarial worm Brugia malayi. These peptides in solution adopt helical structures closely resembling that of ShK. At doses in the nanomolar–micromolar range, they block native Kv1.3 in human T cells and cloned Kv1.3 stably expressed in L929 mouse fibroblasts. They preferentially suppress the proliferation of rat CCR7⁻ effector memory T cells without affecting naive and central memory subsets and inhibit the delayed-type hypersensitivity (DTH) response caused by skin-homing effector memory T cells in rats. Further, they suppress IFNγ production by human T lymphocytes. ShK-related peptides in parasitic worms may contribute to the potential beneficial effects of probiotic parasitic worm therapy in human autoimmune diseases

A less heavy summary is here:-

'Wormpill' could ease autoimmune disease symptoms

  

The researchers noted that Kv1.3 is widely regarded as a therapeutic target for immunomodulation in autoimmune diseases.

So it seems that they have identified the mechanism of action of the worms.

Earlier posts have mentioned intentionally swallowing TSO parasites (Helminthic therapy) for autism and the trials now ongoing by Coronado Biosciences.   Here is part of one post:-

I think that TSO is very interesting.  It is now being developed by Coronado Biosciences as a therapy for several inflammatory conditions including:-

·        Crohn’s disease

·        Ulcerative Colitis

·        Autism

Here is a link to all the clinical trials they are running.

The idea behind TSO is that the parasites have evolved a method of ensuring their survival in their host, by subduing the immune system, so that they are not killed/ejected.  By down-regulating the immune system, they become a therapy for diseases featuring an over active immune system.

This all started a few years ago when one autism Dad figured all this out and tried it on his own son.  Then began the long process of clinical trials, which then ended up with Coronado Biosciences.  The Dad’s website is here.

The Australians have the idea of making their (ShK)–related peptides into a drug therapy.  So no need to swallow those worms after all.

Verapamil or Stichodactyla helianthus toxin (ShK)–related Peptides

Just as the Australians may have trumped Coronado Bioscience with their better-than-a-worm peptide pill, has Verapamil the ability to trump the Ozzies?

We know that Verapamil is neutralizing many allergic reactions affecting autism all over the body.  This appears to be a combination of mast cell stabilization and a possible effect on pancreatic function that reduces GI problems.  But is Verapamil’s inhibitory effect on Kv1.3 also providing a broader immunomodulatory effect as well?  It does indeed look possible.

We would need somebody using TSO worms for autism, to see if Verapamil was effective for them too.  Any volunteers?

Unlike the TSO worms and the ShK peptides, Verapamil is cheap and sitting on the shelf in your local pharmacy.

Cognitive Function Restored, with Bumetanide

Regular readers will know that every summer Monty, aged 11 with ASD, has a “flare-up” in his autism.  Behaviour gets very much worse and now we notice that also cognitive function is impaired.

In my last post I repeated how the aggression and SIB (self-injurious behaviour) was very effectively suppressed by Verapamil and I was pondering how to solve the, now visible, cognitive decline.

I suppose some readers may be thinking all this sounds fanciful.  Once a child with autism is verbal and has got as far as basic maths, it is very easy to measure cognitive function.  For years I have asked Monty what he had for lunch at school that day, to check how “switched-on” he was.  Now, I just need to ask him something like “what is five times five”.

Ted, Monty’s older brother, has also noticed these changes and has recently delighted in showing how his brother does not know six times six, or even twelve plus five.  He would ask him questions when we are all in the car, and then I would have to start making excuses for his brother.  Well with Verapamil, at least Ted is not going to get punched by Monty, as they sit in the back of the car.

We know that for most of the year Monty knows the right answer to all these questions, but from July to early October he may get them wrong, or does not answer.  This was all traced back to the effect of a mild pollen allergy.

Rather than look for something new, I decided that as a first step I would just increase the dose of one of his existing Polypill ingredients and “hey presto” the problem was solved.  A nice surprise, indeed.

I increased the Bumetanide dose from 1mg once a day, to 1mg twice a day.

Every time since that I ask Monty five times five, or six times four he gets the right answer, even if he is in the middle of doing something else, like jumping into the swimming pool.  That is proof enough for me.  Even Ted has noticed.

In previous posts I did complain about the effectiveness of autism rating scales and suggested that measuring academic performance (in older kids) might be more reliable.   In the case of Bumetanide this really is the case.

As to the relationship between bumetanide and allergy, there are various possibilities.  I did yesterday highlight this impact to the French researchers currently working to get Bumetanide approved officially as drug for autism, since it could be useful for them to know.

Conclusion

So, the current summertime allergy solution is:-

Aggression and SIB – Verapamil three times a day

Cognitive impairment – Bumetanide one extra daily dose of 1mg

All that is left of the “autism flare-up” is a very occasional rapid mood swing from happy to sad.

Compared to last summer, the difference is profound and now the difference between behaviour in summer and winter is very small.

  

Allergies, Autism and Cognitive Impairment

Previous posts showed how pollen allergies can lead to summertime flare-ups in autism; most noticeable are violent/aggressive behaviours, but there is actually much more going on.

I established that Verapamil, the calcium channel blocker, and surprisingly also a mast cell stabilizer, can very effectively extinguish the aggression, but without really solving the usual allergy symptoms like itchy eyes.  As a result, you need to use a convention anti-allergy treatment as well.

Asthma/Pollen Hot Spots

Any asthma suffer will be able to tell you about the places that make them feel worse and the places that places that reduce their symptoms.  It seems that pine forests high in the mountains and on certain coastlines are best.

Forested areas around cities are not good for asthma, Berlin being an example. So you can easily check if you live in an asthma hot spot, or in a better place.

Cognitive Impairment

We just spent two weeks under the olive trees beside the sea in Greece, which I would classify as a low pollen location.  Having returned home to a big city and a house directly opposite a forest, we could see the effect of an asthma/pollen hot spot.

Monty, aged 11 with ASD, mild pollen allergy and mild asthma, did change his behaviour almost immediately.

The Verapamil does continue to block aggressive behaviour, but what changed was an immediate return of mild atopic dermatitis (red patches behind knees) and what Monty’s brother Ted, aged 14, described as Monty became “more stupid”.  It is not a nice way to describe it, but when you look closely, it is there.  The allergy has effectively lowered his cognitive function.  It is very easy to check, just ask some simple maths questions or memory questions (what did you have for breakfast?).  It is as if he is very mildly intoxicated (drunk), he is not staggering around, but he is not as sharp as he was in Greece, or at home in the spring.

Faced with an aggressive child, the last thing you would bother about is how good he is at mental maths, and so you would probably never notice it.  But having solved the aggression we are left with the observation that the allergy causes some temporary cognitive impairment.  I say temporary, because if you take away the allergens, everything improves and returns to where it was.

What is going on?

We know that allergens cause mast cell degranulation, which releases histamine, IL-6, and other pro-inflammatory substances in a chain reaction.  We know that these cross the BBB (blood brain barrier) where there are several types of histamine receptor.  The body has at least 4 types: - H1, H2, H3 and H4, and maybe more not yet identified.

Typical anti-histamines only block H1, and the newer ones are specifically designed not to cross the BBB, so as not to make you drowsy.  We later discovered that most H1 anti-histamines have moderate mast cell stabilizing properties, meaning they do reduce the release of histamine itself.

Calcium channel signaling is known to be disturbed in autism and there is excess physical calcium found in the autistic brain.  This did suggest that modifying calcium channel behaviour might be of benefit.  A known genetic variation in autism does affect the L-type calcium channels.  This suggested that blocking the L-channels might be helpful.  This was shown to be true in Timothy syndrome and I showed it to be true in Monty.

Other research has shown that Verapamil is an effective mast cell stabilizer, which did come as a surprise.

Now we come back to the effect of the allergy.  If untreated, it will “dumb down” the child and also lead to extreme behaviours like aggression, but also even odd physical tics, like moving the head forwards and backwards like a pigeon.

Perhaps there is a two stage process going on, which ultimately leads to the aberrant signaling of the L-type calcium channels and aggression.  Or is it just a progression from mild to severe?

Is it a coincidence that a calcium channel blocker can stabilize mast cells?  I think it unlikely.

Autism as an Allergy of the Brain

The idea put forward by Professor Theoharides, that autism is, at least in part, an allergy of the brain, looks more and more valid.  It was the subject of an earlier post.

Is a Subtype of Autism an Allergy of the Brain?

I do wonder how much mental retardation (MR) / cognitive impairment is also caused by the same mechanism.  Depending on how you define “autism” and whose figures you use, between 20% and 50% of people with autism have MR.  MR is defined as an IQ of 70 or less.

·        Mild retardation: Mild retardation: IQ level 50-55 to approximately 70 (85% of people with mental retardation are in this category)
·        Moderate retardation: IQ level 35-40 to 50-55 (10% of people with mental retardation)
·        Severe retardation: IQ level 20-25 to 35-40 (3 - 4% of people with mental retardation)
·        Profound retardation: IQ level below 20 or 25 (1 - 2% of people with mental retardation)

I would suggest that many people with autism might be “cognitively impaired” by allergies, be they caused by pollen, cats, dust, food, detergents, pollution or anything else.  Maybe they just dropped from a potential IQ of 120 to 110, or maybe they dropped from 80 to 35 and are now known as severely retarded.

Verapamil treats more than aggression and SIB

Based on my sample of one, it would be conceivable that Verapamil merely treats aggression and self-injurious behaviour (SIB), and that allergies are a side issue.  But thanks to the feedback on this blog, it is clear that Verapamil is treating the allergy.  One reader gave very extensive feedback showing how Verapamil greatly reduced her child’s GI problems (caused by food intolerance/allergies) and improved behaviour.  So based on a sample of two, Verapamil’s effect does seem to be related to mast cell degranulation and allergies.

Conclusion

I am very happy to have discovered the benefits of Verapamil, but I will continue to look into how further to reduce the “brain allergy effect”.  Perhaps the allergy is somehow affecting the excitatory/inhibitory balance of the Neurotransmitter GABA, I say this because Monty’s behaviour somehow resembles life without Bumetanide.  

Bumetanide’s role in autism is to lower brain Cl^- concentration and to switch GABA to be inhibitory.  A recent comment on one of my Bumetanide posts was from somebody highlighting a paper that questioned whether enough Bumetanide crosses into the brain to switch GABA to be inhibitory.  

Note that a recently published comprehensive review on the use of bumetanide in the treatment of neonatal seizures indicates that theres is no evidence to support the use of this drug in the treatment of central nervous system disorders via the NKCC1-dependent mechanism described above, as at the very low doses that are given to infants and children bumetanide does not reach sufficient levels in the brain.

direct link to the original review:
http://onlinelibrary.wiley.com/doi/10.1111/epi.12620/pdf

It is conceivable that allergies affect the blood brain barrier (BBB), although you might expect allergies to weaken the BBB, rather than strengthen it; but the body does plenty of strange things.  So a second daily dose of Bumetanide just might help.  In France, the autism researchers working with Bumetanide do give it twice a day.

The simplest method to reduce the “brain allergy effect” would be to just avoid the allergen(s).  In the case of Monty, this would be to go and live in a low pollen environment, and perhaps even avoid cats.

Since 30+% of people with autism apparently suffer from asthma, then 30% of people with autism might also find behavioral relief by avoiding pollen.  Those suffering from aggression and SIB would very likely benefit dramatically from Verapamil.

This might also suggest that residential facilities for people with severe autism should be in low pollen areas.

Incidentally, our local special needs school used to be surrounded by a rampant overgrowth of ragweed/ambrosia.  This is one of the most notorious plants for causing allergies in humans.  The current number 1 in the ATP world tennis rankings then gave them some money to tidy up the grounds.  Coincidentally, like many of the “inmates”, he also favors a gluten free diet.

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.

Carnosine for Autism – an Alternative to N-Acetylcysteine (NAC)? or is it Complementary?

Several people have mentioned to me a supplement called L-Carnosine, so I thought it was worthy of its own post.

The first thing to note is lots of supplements have very similar names and indeed two entirely different substances are abbreviated to NAC.

·        Carnosine

·        Carnitine

·        L-Carnosine

·        L-Carnitine

·        N-Acetylcysteine    (abbreviated to “NAC”)

·        N-Acetylcarnosine  (also abbreviated to “NAC”)

In this blog, and in most literature on autism, NAC refers to N-Acetylcysteine.

This post is about Carnosine and L-Carnosine, but there is also research on the use of Carnitine and L-Carnitine regarding autism and Retts syndrome.  So double check what is on the label, if you do indeed order some.

Vladimir Gulevich, Carnosine (and Carnitine)

Vladimir Gulevich  received the degree of doctor of medicine in 1896 from the department of medicine of Moscow State University. From 1900, he rejoined the Moscow State University where he was rector for a brief period of time in 1919. He was a full member of the USSR Academy of Sciences since 1929.

Gulevich discovered both Carnosine and Carnitine in his work in Moscow.  Even today his university is a centre of research for both these substances.

Carnitine and carnosine are composed of the root word carn, meaning flesh, alluding to its prevalence in animal protein. A vegetarian (especially vegan) diet is deficient in adequate carnosine, compared to levels found in a standard diet.

Researchers in Britain, South Korea, Russia and other countries have shown that carnosine has a number of antioxidant properties that may be beneficial.

Carnosine has been proven to scavenge reactive oxygen species (ROS) as well as alpha-beta unsaturated aldehydes formed from peroxidation of cell membrane fatty acids during oxidative stress.

Carnosine can chelate divalent metal ions.  DAN Doctors probably do not know what divalent means, but in Hg²⁺ the “2” means divalent and Hg means mercury.

Carnosine was found to inhibit diabetic nephropathy.

Carnosine-containing products are also used in topical preparations to reduce wrinkles on the skin.

Some studies have detected beneficial effects of N-acetylcarnosine in preventing and treating cataracts of the eyes.

Carnosine and Autism

Small studies, including this one by Michael Chez, have shown the benefit of L-carnosine in autism.  By the way, Chez seems to be one of the handful of genuinely knowledgeable autism clinicians anywhere on the planet.

Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders.

Abstract

L-Carnosine, a dipeptide, can enhance frontal lobe function or be neuroprotective. It can also correlate with gamma-aminobutyric acid (GABA)-homocarnosine interaction, with possible anticonvulsive effects. We investigated 31 children with autistic spectrum disorders in an 8-week, double-blinded study to determine if 800 mg L-carnosine daily would result in observable changes versus placebo. Outcome measures were the Childhood Autism Rating Scale, the Gilliam Autism Rating Scale, the Expressive and Receptive One-Word Picture Vocabulary tests, and Clinical Global Impressions of Change. Children on placebo did not show statistically significant changes. After 8 weeks on L-carnosine, children showed statistically significant improvements on the Gilliam Autism Rating Scale (total score and the Behavior, Socialization, and Communication subscales) and the Receptive One-Word Picture Vocabulary test (all P < .05). Improved trends were noted on other outcome measures. Although the mechanism of action of L-carnosine is not well understood, it may enhance neurologic function, perhaps in the enterorhinal or temporal cortex.

As Dr Chez points out, nobody is 100% certain why it is of benefit.  It could just be the anti-oxidant properties of carnosine or it could be something related to the interaction between carnosine and GABA in the brain.  GABA is an important neurotransmitter in the brain.

Other GABA related drugs show a positive effect in types of autism.  These include Baclofen, Arbaclofen, Bumetanide, Clonazepam and even Valproic acid (VPA).  The underlying mechanisms do differ, but all relate, in one way or the other, to GABA.

The Carnosine dosage used by Dr Chez was 800mg per day.

The body deploys a range of enzymes, called carnosinases, to break down carnosine.  In order to maximize the effect, and out-smart the  carnosinases, it might be wise to split the dose into two per day.

In a perfect world it might be simpler to inhibit the carnosinases and just rely on the carnosine from meat in the diet.

You cannot patent naturally occurring substances, so nobody can patent carnosine and no drug firm will therefore research it.  A carnosinase inhibitor could be patented and therefore could be made into a drug.

Carnosine and GABA

It looks like Moscow State University is still the centre of knowledge for Carnosine and Alexander A. Boldyrev recently published a book called:-

Carnosine and Oxidative Stress in Cells and Tissues

Book Description:

The main aim of this new book is to summarize the knowledge on the metabolic transformation of carnosine in excitable tissues of animals and human beings and to analyze the nature of its biological activity. At the beginning of monograph, the short history of the problem is stated. Distribution of carnosine in tissues, its appearance in ontogeny of vertebrates and correlation between carnosine content and functional activity of tissues are discussed. Chemical properties of carnosine and its natural derivatives and their ability to bind heavy metals and protons in water solution are documented. Special attention is paid to free radical quenching ability and to anti-glycating action. Biological activity of carnosine and carnosine containing compounds was tested using biological models of several levels of complexity, starting from individual enzymes and acellular mixtures and finishing to living cells and survival animals. Effects of carnosine on the whole animals under ischemic, hypoxic and other extreme conditions are described. In conclusion, the ability of carnosine to protect brain and muscular tissues from oxidative injury during exhausting exercise, extreme loading or neurodegenerative diseases is demonstrated. Based on these properties, carnosine is postulated to be a potent protector of human beings from oxidative stress.

You can preview much of the book on Google Books

We know from many autism researchers that oxidative stress is a feature of many people’s autism.  Anything that reduces this stress should have a positive effect on behaviour.

Common antioxidants used in autism include:-

·        N-Acetlycysteine (NAC)

·        Alpha Lipoic Acid (ALA)

·        All the many “chelating” substances used by DAN Doctors

Carnosine may be just an alternative anti-oxidant.

However, when you look through Boldyrev’s book, it does look possible that the chemical relationship between GABA and Carnosine many also play a role.

Conclusion

People currently taking Carnosine for Autism might well want to try N-Acetlycysteine (NAC) and see if they notice an additional benefit.  Conversely, the current NAC converts, like my son Monty, aged 11 with ASD, may well want to give Carnosine a try and see what happens.

One blog reader with Asperger’s finds Baclofen highly beneficial; he might as well give Carnosine a try, based on the GABA relationship.

Current research indicates 2,400 mg of NAC and 800 mg of Carnosine. 

It would be nice if one day somebody would do a controlled trial of NAC vs Carnosine vs Carnosine+NAC;  but don’t hold your breath.

Some people with diabetes are already taking ALA (Alpha lipoic acid) or Thioctacid for neuropathy, but find it also increases insulin sensitivity; this means they need less insulin.  They might well find both NAC and Carnosine will further increase insulin sensitivity.  Generally speaking it seems that low insulin sensitivity is bad and high insulin sensitivity is good; but I am no expert on diabetes.

In some counties Carnosine is not available, but you simply can buy it online on Amazon, ebay or many other sites. 

More on Carnosine from Harvard Medical School