Thursday, 30 April 2015

Autism and Deafness? Then no Cochlear Implant for You

Monty, now aged 11 with ASD, has an assistant who comes in the afternoon to run our ABA-inspired home program, let’s call her Stella.

Stella is a student training to be a teacher for deaf people, so her knowledge of ABA comes from her time with Monty.  Nobody here uses ABA to teach the deaf.

Her latest task was to try and teach 3 eight year old children to count to ten.  The problem being that two of the children are deaf and can only say “yes” and “no” and the third child is deaf, autistic and non-verbal.

Using ABA she managed to teach the two deaf children to count out loud to ten and to match objects marked with each number.  Very good and the regular teachers were very impressed.

My comment was that it was a pity nobody taught them to say something more useful.  How about “hello”, “my name is Tom” etc.

What about the deaf boy with autism?  It turns out, where we live, if you are deaf and have other “complex needs” you do not get a cochlear implant.

Cochlear implants, when implanted while the deaf person is very young, can be hugely successful.  About 400,000 people worldwide have received them.  You end up with a different kind of sound than that experienced by non-deaf people, but it gives the brain inputs which allow it to identify and process speech and other sounds.


Cochlear implants for congenitally deaf children are considered to be most effective when implanted at a young age, during the critical period in which the brain is still learning to interpret sound. Hence they are implanted before the recipients can decide for themselves, on the assumption that deafness is a disability.

Children with cochlear implants are more likely to be educated orally, in the standard fashion, and without access to sign language (Spencer et al. 2003). They are often isolated from other deaf children and from sign language (Spencer 2003). Children do not always receive support in the educational system to fulfill their needs as they may require special education environments and Educational Assistants. According to Johnston (2004), cochlear implants have been one of the technological and social factors implicated in the decline of sign languages in the developed world.

Cochlear Implants and Autism

Since people with autism have various sensory issues, they are not considered suitable candidates for the only therapy that could give them the ability to hear.  At least that is the case in many countries.

The word is that in the first year it is hard to adjust to a Cochlear Implant and this is one reason why they have to be implanted while the person is very young.  It takes the brain a while to adjust, and the more plastic it is, the better it can adjust.

Since people with autism are not exactly flexible at the best of times and they can be prone to tantrums and violence, they are seen as a challenge too far.

This seems rather cruel to me and very short sighted.

As Stella said:- “for that first year, who is going to look after them?”

My response would be “who is going to look after them for the next 60+?”

After all, would you rather care for a sometimes violent toddler for 12 months during his adaptation to hearing, or a sometimes violent, deaf autistic adult for life?  I suppose they just drug the adults.

How common is deafness with autism?

According to some research, about 5% of people with deafness have autism and about 3.5% of people with autism have deafness.

I think when they say “autism” they mean serious autism, not the modern, all-inclusive, DSM 5 autism-lite.

What does the Research tell us?

As always, there is data on just about everything and this includes autism with deafness and the efficacy of Cochlear Implants.

Rather as I expected, it is not true that giving hearing to deaf people with autism is a bad idea.  The research actually shows the opposite.

Just as teaching deaf people to count aloud is possible, when you apply simple behavioral techniques, so is giving hearing to deaf people with autism.

Results: Fifteen patients with history of ASD and cochlear implantation were analyzed and compared with 15 patients who received cochlear implant and have no other disability. Postoperatively, more than 67% of children with ASD significantly improved their speech perception skills, and 60% significantly improved their speech expression skills, whereas all patients in the control group showed significant improvement in both aspects. The top 3 reported improvements after cochlear implantation were name recognition, response to verbal requests, and enjoyment of music. Of all behavioral aspects, the use of eye contact was the least improved. Survey results in regard to improvements in patient interaction were more subtle when compared with those related to sound and speech perception. The most improved aspects in the ASD patients' lives after cochlear implantation seemed to be attending to other people's requests and conforming to family routines. Of note, awareness of the child's environment is the most highly ranked improvement attributed to the cochlear implant.

Conclusion: Cochlear implants are effective and beneficial for hearing impaired members of the ASD population, although development of language may lag behind that of implanted children with no additional disabilities. Significant speech perception and overall behavior improvement are noted.

"Although the group of deaf children with complex needs is overall a heterogeneous one, there are subgroups that would benefit from further and detailed investigation in thinking about cochlear implantation, for instance deaf children with Down’s syndrome, Children with Autistic Spectrum Disorder, cerebral palsy."


Monday, 27 April 2015

RAS signaling, Autism, Cancer and Gingerols

Sytrinol (Tangeretin), sacrificial Gummy Bear and Gingerol








RAS-based interventions


• Treatment of cognitive dysfunction associated with NF1
• Treatment of cognitive dysfunction associated with Noonan syndrome
• Effectiveness in restoring cognitive function has been demonstrated in vivo


The studies using Lovastatin were positive:-



There is a comprehensive presentation from Silvalab at UCLA below,


So choose your statin with care. 




Statin MAX



Gingerols in “Medicine”



Swallowing Pills






In the end it was a non-event.



This was swiftly followed by the rather odd smelling gingerol capsule.



·        Asthma*
·        Ulcerative Colitis*
·        Arthritis *
·        Alzheimer’s Disease
·        Cancer*





Clinical Relevance





Ulcerative Colitis







Microglial Activation


8. Gingerol from Zingiber officinale


Alzheimer’s Disease

















·        Statins

·        Gingerols


Thursday, 23 April 2015

Buy Arbaclofen for Autism? Perhaps try Pantogam Aktiv?

An Enantiomer is like a mirror image,
so there are two versions of the “same” molecule one called R- and one called  S-

Some people are still looking to obtain Arbaclofen to treat autism and Fragile-X, they regularly stumble upon this blog.

A couple of years ago there was a lot of interest in Arbaclofen (R-baclofen), a GABAB drug, which is, in effect, a special version of a cheap existing drug called Baclofen.  Baclofen is generally used to treat spasticity, but also alcoholism and even hiccups.

As we saw in earlier posts, the drug Baclofen is a mixture of R-Baclofen and S-Baclofen. The research showed that their action is different and that S-Baclofen reduced the effect of R-baclofen.  So in some modes of action, pure R-Baclofen would have much greater effect than the regular Baclofen mixture.

If you use the "index by subject" on this blog, which is a tab at the top, you can find the posts that relate to Arbaclofen.


Arbaclofen Research in Autism/Fragile X

This very expensive episode was triggered by one child with autism being prescribed regular Baclofen, for an unrelated issue.  That child’s autism had dramatically improved, this then led to the interest of Seaside Therapeutics, who already had another prospective autism drug.

After tens of millions of dollars spent, everything stopped a couple of years ago.  The developer, Seaside Therapeutics, appears to have been shut down, although in its clinical trial a substantial minority found the drug was effective.  The way the trial had been structured, the drug did not achieve is “primary endpoint” and so Roche, the potential follow-on investor, deemed the trial a failure.

This led to many unhappy parents seeking alternative sources of R-Baclofen, which they believed had been effective.

Baclofen for Asperger’s?

At least one regular reader of this blog finds that Baclofen is very helpful for himself.

Yesterday before completing this post I had some exchanges with a UK pediatrician (spelled paediatrician in the UK) who is prescribing Baclofen to eight children with Asperger’s to treat anxiety. The results are very positive.  I do wonder is this a 100% response rate,  or are the eight a subset of all the children that have tried the drug?

One of our Australian readers of this blog is very interested in minimizing anxiety in his child with high functioning autism.  He did forward me some research, a while back,  that links GABAB to Somatostatin, also called Growth Hormone Inhibiting Hormone (GHIH) .  The research from Carnegie Mellon shows that GHIH changes the way the brain functions. 
This does get very complicated the more you dig and, until today, I did not start to write up my findings.  This is just some initial thoughts/links for scientists.

“If the levels of human growth hormone in circulation in the brain and the blood get too high, then special cells called somatostatin neurons detect this. These neurons then trigger the creation of more GHIH in the brain. This then in turn slows down the secretion of human growth hormone.”

 “Mature interneurons from this brain region mainly express either parvalbumin or somatostatin, which serve as markers of these subtypes. Parvalbumin neurons tend to fire quickly in response to signals, whereas the somatostatin ones respond more slowly.
In control mice, the ratio of these two subtypes is about 50:50. By contrast, the mutant mice show a dramatic decrease in the number of interneurons expressing somatostatin. This results in an excess of abnormally large cells expressing parvalbumin.
Despite an overall loss of interneurons, the mice have more inhibitory signals than controls do, skewing the signaling balance to excitation.” 

We do know that the various growth factors in people with autism can be disturbed, but in different types of autism that disturbance varies, just to complicate things.

Various therapies based on this are under development (one uses IGF-1 and NNZ-256 is another).  We also know that many people with classic autism have accelerated growth (both body and head) in the first two years.  We also know that brain growth is also accelerated.

We know from the genetic research that many of the anomalies relate to GABA.

We know that targeting the GABAA receptor can be hugely beneficial in classic autism (bumetanide and micro-dose clonazepam).  We can also fine tune the structure of the GABAA receptor and potentiate it using allosteric modulators (like Pregnenolone or progesterone).  This also gets very complicated.

Baclofen for Classic Autism?

Baclofen is a spasticity drug:

Spasticity (from Greek spasmos-, meaning "drawing, pulling") is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles.

People with (classic) autism as opposed to Asperger’s can have all sorts of fine and gross motor issues, particularly as young children.

They can “toe walk”, walk with their feet pointing in different directions, they can have “claw hand”.  They can struggle to control a pencil and even when they learn, their handwriting can be very sloppy.

Are these spasticity issues?  I think they probably are.

When people’s autism flares up, an early sign is worsening handwriting.

When my son’s Polypill begins to wear off in spring/summer at school at around 11 am, the claw hand returns.

I did indeed try Baclofen about a year ago.  There is an effect - no claw hand.

The problem with Baclofen is tolerance, the more you use it the higher the effective dose becomes, just like benzodiazepines.

So I noted that there was an effect, but chose to move on.

Meanwhile over in Russia

For many years in Russia they have had their own GABAB drug, similar to Baclofen, it is called Pantogam.  Pantogam has been used for years as a therapy for neurological conditions including autism.

Just as Baclofen is “racemic mixture” of left-baclofen and right-baclofen, so is Pantogam.  There is S-Pantogam and R-Pantogam.


There is nothing strange about these left and right versions of a drug

Enantiomers of each other often show different chemical reactions with other substances that are also enantiomers. Since many molecules in the bodies of living beings are enantiomers themselves, there is sometimes a marked difference in the effects of two enantiomers on living beings. In drugs, for example, often only one of a drug's enantiomers is responsible for the desired physiologic effects, while the other enantiomer is less active, inactive, or sometimes even responsible for adverse effects.

Another good example is a common antihistamine:-
Levocetirizine (Xyzal) and cetirizine (Zyrtec)
Cetirizine, an effective H1-receptor antagonist, is a racemate mixture of two enantiomers: levocetirizine (R enantiomer) and dextrocetirizine (S enantiomer).  Chemically, levocetirizine is the active enantiomer of cetirizine. It is the L-enantiomer of the cetirizine racemate.
Cetirizine is sold as Zyrtec and Levocetirizine is sold as Xyzal.

If you prefer Claritin:
Claritin is loratadine.  The active half of this mixture is desloratadine.
So they have separated this out and produced a single-enantiomer drug made exclusively of desloratadine.  You can buy this as Clarinex/Aerius, depending on where you live.

In many cases the single-enantiomer drug works no better, it just costs more and may allow for a patent to be extended, which may mean billions of extra dollars.

Single-enantiomer drugs: elegant science, disappointing effects.
Most new drugs are marketed as single enantiomers but many older agents are still available in racemic form. As these drugs reach the end of their patent life manufacturers become interested in marketing single enantiomer equivalents. This is called 'chiral switching' and it has been claimed that it will bring clinical benefits in terms of improved efficacy, more predictable pharmacokinetics or reduced toxicity. We reviewed the clinical evidence and prices for three recently marketed single enantiomer versions of widely used racemic drugs: escitalopram, esomeprazole and levosalbutamol. Claims of increased efficacy were based on comparisons of non-equivalent doses and any advantages seemed small and clinically unimportant. Prices of esomeprazole and levosalbutamol were higher than their racemic alternatives and we predict that these prices will remain high despite the market presence of generic versions of the racemates. Patent protection and a perception of superiority based on promotion rather than evidence will maintain price premiums for single enantiomer drugs that are not justified on the basis of clinical performance

Back to Russia

In Russia they have now marketed the single enantiomer drug of Pantogam, which is called Pantogam Aktiv.
Does Pantogam Aktiv work “better” than Pantogam, or does it just cost more?
Is Pantogam Aktiv equivalent to R-baclofen (arbaclofen)?

How would those eight kids with Asperger's in the UK fare on Pantogam Aktiv, as opposed to Baclofen?  Is tolerance an issue with Pantogam Aktiv? 

“Failed” Arbaclofen Trial
Rather than spend tens of millions of dollars on Arbaclofen, why did not someone just think of first trying Pantogam and Pantogam Aktiv on that very first child who responded to Baclofen?
When they closed the trial (and the company) why did they not suggest to those unhappy parents to try Pantogam and Pantogam Aktiv?

Pantogam Research
Most research is in Russian, but there is some in English.  Interestingly this drug affects both GABAA and GABAB.
While its main effect is on GABAB. like Baclofen, it also has the effect of modulating the GABAA response.  This effect means that when combined with benzodiazepines, where normally people build up a tolerance, and so the dose needs to be increased, no tolerance develops.  We saw this very effect on GABAA with tiny doses of other drugs in earlier posts.

 A total of 32 children aged 6–12 years with attention deficit hyperactivity disorder (ADHD) were monitored during prolonged (6–8 months) treatment with Pantogam (homopantothenic acid) at daily doses of 500–1000 mg. Treatment results were assessed using the DSM-IV core ADHD symptom scales and the WFIRS-P (parental) scale every two months. Decreases in core symptoms on the DSM-IV core ADHD symptom scale were seen at two months of treatment. Significant changes on the WFIRS-P scale took longer: improvements in self-concept, socialization, and social activity were seen at four months and in behavior and schoolwork, basic life skills, along with decreases in risk-associated behavior, at six months. Thus, in contrast to regression of core ADHD symptoms, overcoming impairments in social-psychological adaptation required longer treatment periods.

Arbaclofen (R-Baclofen) failed its clinical trial, so it is no wonder drug for Fragile X and classic autism, but is was effective in a minority of people. 
It is possible that it would have been much more effective on people at the other end of the spectrum, those with Asperger’s – like the reader of this blog and the UK pediatrician using cheap Baclofen.
The people behind the Arbaclofen trial were super-brainy types from MIT, dig a bit deeper and I recall family links to Fragile-X.  So objectivity went out of the window, along with all those millions of dollars.
I do not suppose Pantogam and Pantogam Aktiv are autism wonder drugs, but they must help in some cases, otherwise the Russians would not be prescribing them. 
For those who found Arbaclofen really did help, why not try Pantogam and Pantogam Aktiv?  Just use Google:- “Buy Pantogam” in place of “Buy Arbaclofen”.
You would have thought someone smart at the US NIMH would have thought of this.  There are some very clever Russians and they do have autism over there too.