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Sunday 27 December 2020

Inappropriate Behavior in Autism


Green choices and red choices.  You get to decide.

 

I was recently asked by a friend, who teaches social skills to young people with autism, how we have dealt with inappropriate behavior in our son Monty, now aged 17.  The short answer was “we have not had to”.  The longer answer is more complex.

First of all, you have to figure out what kind of “Inappropriate Behavior” is in question.  I consider lots of natural behavior in autism to be inappropriate - stimming, flapping, scripting, the obsessive desire for sameness and repetition and an apparent aversion to following rules and instructions, for some people.

Of course, I guessed what the immediate question was actually about - sexually inappropriate behavior, this time in a 12-year-old boy. These issues have been raised in the comments section of this blog on many occasions.

The underlying problem is not something that developed at puberty, it is just a consequence of what has happened (or rather, not happened) in the years since the child was a toddler.

Typical children learn by being taught by their parents and teachers, but significantly also by observing others and how they behave.

Even very severely autistic people can be taught basic things, but when it comes to learning by observation and picking up unspoken rules, they can be completely lost.  They need to be taught basic rules and those rules have to become instinctive, over 18 years of childhood.

The most basic inappropriate autistic behavior referred to is undressing in public.  When Monty was 3 years old, we were asked to provide an Assistant in the kindergarten, because he was taking his clothes off.  The teacher did not want the other kids to use their built-in imitation skills and following suit – we do not live in Denmark.  The idea of stripping off in public was nipped in the bud, so to speak.

If you go to the beach in many countries you will see many kids running around naked.  If you go to a park in a big German city you will see office workers, half-naked working on their sun tans, during their lunch break.  The rules of what is acceptable vary widely, depending on where you live.

You can teach a person with severe autism from early childhood that you can only remove your clothes in certain “safe” places.  If you do not do this, then do not be surprised when you, and your teenage son, get into trouble at school because he took his clothes off in the classroom and started playing with himself.  This was what happened with the 12-year-old in question.

The worse thing is that some parents then want to use drugs to halt these “inappropriate behaviors”, that they have allowed to develop.

 

Medical Therapy for Inappropriate Sexual Behaviors in a Teen With Autism Spectrum Disorder

Teens with autism spectrum disorder often exhibit sexual behaviors in public that are disturbing to parents, teachers, and peers. Some have proposed that such behaviors can be curtailed with hormonal suppression. There is information on the Internet suggesting that such medications work, and some reports in the peer-reviewed medical literature support these claims. Such medications can have serious side effects. In this paper, we present a case in which parents requested such treatment of their teenage son with autism spectrum disorder.

 

The most basic skill that needs to be taught to a person with severe autism is to follow the instructions of the supervising adult.  The child is not the boss.

When I take my son to the dentist, he has to follow her instructions.  If he does not follow my instructions, how can he ever follow those of the dentist?

Our friend, figuring out what to do about the problematic 12-year-old, can see that there is plenty written about the subject, like this presentation from Australia. 


SEXUAL BEHAVIOURS OF CONCERN IN YOUNG PEOPLE WITH AUTISM SPECTRUM DISORDERS


My own opinion is that if you treat your child with severe autism in a similar way to his/her siblings you will not go far wrong.  Do not soften those rules/expectations.  You set very simple rules and apply them consistently.

When it comes to neurotypical children, different parents apply completely different rules.  This also has consequences, but neurotypical children are much more resilient to the mistakes of their parents.  You can make mistakes and be forgiven later!

With autism, it is very much a case of you reap what you sow.

There was a case recently in the US of an autism advocate mother.  She wrote how she could not take her adult-sized son swimming, because her friends with pools no longer want him to visit.  Her son had a habit of removing his clothes and also peeing in people’s gardens.  That might be funny if it was a 3-year-old, but people do not like it in an adult sized person – that clearly does count as inappropriate behavior.  OK, the boy is autistic and so he gets to do things the way he wants; the mother is not in control of her son’s behavior and the consequence is no pool parties – no big deal, you might think.  Recently, the family’s house caught fire and the whole family escaped the two-storey building, except for the boy.  The mother then goes back into the house and tries to negotiate with the boy to leave his bedroom and come outside.  Unfortunately, what was reportedly heard outside was the boy shouting “No! No! No!”. The boy, autistic or not, should have instinctively followed the parent’s instruction, instead the boy and his mother died in the fire.

In females with autism, aggressive behavior and indeed seizures can be triggered by cyclical hormonal changes that do not affect boys.  Treating boys to supress their hormones to minimize inappropriate behavior looks pretty desperate.  

It is fashionable to indulge people with autism and let them express/develop all kinds of behaviors.  It is unfashionable to take the other path and promote doing your best to fit in with what society considers as normal.  If you look at the nature that surrounds us, it is driven by evolution and evolution is driven by adapting to your surroundings.  Sulking about how you do not like your surroundings might get you likes and retweets, but sets you on a path to extinction.  

      

Inappropriate Behavior in Autism, or is it Misguided Parenting?

Parents do need help and that is why my friend is helping to teach their children social skills.  Autistic children do not yet come with an instruction manual. “Mistakes”, though made with the best of intentions, will have life-long consequences.

 

Touching Others

I was surprised how many children, even with mild autism, like touching other people’s hair.  A girl in my elder son’s class used to get very upset by an Aspie boy who kept touching her hair; she felt she had a stalker. The concept of “personal space” is something you have to teach, even to some Aspies.

Monty also likes nice hair – pigtails and ponytails in particular. But he was taught that you have to ask, if you want to touch.  The girls in Monty’s class at school actually seem to like the fact that he notices and appreciates their hair. 

When it comes to hugging, kissing and hand shaking, conventions are so different among different nationalities/cultures things get confusing. Some greetings, common in countries like France, would not go down well in Anglo-Saxon countries. 

 

Be as normal as possible and avoid cocooning

One reason people with autism have strange behaviors is they live very protected lives, often overly protective.  If you don’t get out much, you will not learn how to behave, or navigate the world.

I got asked can Monty go to the arcade and play on the virtual reality games, the ones with headsets.  I then say yes, why not?  Then I get told some parents do not allow it, because they think it will make their child with autism have seizures.

Monty’s big brother does competitive shooting.  He wanted to teach Monty how to shoot Grandad’s old army pistol.  So, they went to an outdoor range and Monty showed he could very responsibly shoot the pistol.  You wear ear protectors, but it is still quite a sensory experience.  He behaved totally responsibly and also hit the targets. Monty later told his classmates at school and they did not believe him.

When Monty turns 18 next year, big brother will be taking him to his favourite Irish Pub.  My elder son did ask me and I said that I have no objections - there will be no reason to treat him differently to any other 18-year-old. It is a rite of passage and fraternal bonding opportunity.

Clearly if you have untreated severe autism, you are unlikely to be safe at a shooting range and you may not want a drink at the Irish Pub.

 

What do the “Experts” in the US tell us? 

I did stumble upon a site in the US giving advice on teaching appropriate greetings to people with autism.


https://www.infiniteach.com/resources/appropriate-vs-inappropriate-greetings-visual-support/ 


I actually thought it was very bad advice.

People with autism tend to be very literal.  The advice pretty clearly says emotions are bad, do not express them.


This free autism resource focuses on how to make an appropriate greeting. Oftentimes students with autism learn a routine and stick with it. When the routine is good - everything is great. But in the case of greetings, a lot of young kids are met with hugs, kisses, and hand holding. This may be great and nurturing at 2 or 3 years of age, but at 12 and 13 it is not so appropriate anymore.

 

I thought this was rather sad advice.

I asked my elder son, aged 20, how he greets his friends - he has them from Azerbaijan to Zimbabwe and, yes, even some from the US.  At University in Italy, girls expect 2 kisses and if you give just one, they will feel cheated.  Where we live, girls technically get 3 kisses, but this takes time and 2 is more common.

A boy refusing to greet a girl with a kiss would be seen as rude.

Hugs are very common, as a key part of the boy-girl greeting.  Monty’s female assistants all hug him. My elder son experiences everything from a mini-hug to a bear hug, depending on nationality, Russians being the coldest and Czechs, apparently, the warmest.

Boy-boy greetings often include a pat on the back, “boy hug”.

At weddings where we live, you would expect the boy-boy kiss, which I find pretty odd.  But you have to bend to the local convention.

With French people, everyone gets a kiss; children even kiss adult guests they do not know, which can look a bit strange.

When it comes to holding hands, all that matters is whether both parties are willing.  Banning hand-holding looks like a sure-fire way to repress emotions and create all kinds of future problems.  

 

Inappropriate Behavior in Aspies

Inappropriate behavior in people with severe autism, or those with intellectual disability (MR/ID), is normally just a public nuisance or embarrassment.  In fully verbal people with normal IQ and some autistic traits, there is much more potential for harm to others.  People with severe autism or MR/ID do not have the capacity to carry out revenge plots on the public. 

Most Aspies do not carry out such actions, but most non-terrorist mass attacks on the public are, it seems, carried out by people of normal IQ with an autism diagnosis.  If you doubt this, just read the news.

The young Aspie who is bullied at school, and has no friends, may dream about setting fire to the school, but does not actually do it.  Due the internet, small groups with strange ideas can nowadays get together and self-reinforce their views. These groups range from the slightly deluded but relatively harmless, like ASAN (Autistic Self Advocacy Network) to the severely deluded and potentially criminal.

As was stated in one very insightful comment in this blog, it is only during early childhood that you can address the behavioral issues and beliefs in people with mild autism.  Once they are older, they have fixed their perception of the world and their place in it.  The time for social skills training for Aspies is when they are very young, before they endure years of bullying/teasing/exclusion during high school.  They may not instinctively have the capacity to find and make friends, but they are perfectly capable of be taught most of these skills.  This is not masking, this is learning.  These are actually survival skills for life.  If your formative years are miserable, that does not set you on a good path to adulthood. 

 

Conclusion

It looks like parents need to invest time consciously teaching their child with severe autism what behaviors are desirable, including the when and where part.

If your house is on fire, you follow your parent’s instructions and get out of the house. Your sensory sensitivities do not matter, you have to tough it out, like going to the dentist without full sedation. Not a bad idea to have a fire drill at home, by the way.

If you spend your whole life in one small town you will need only one set of social rules; if you are a bit more cosmopolitan, you will have to understand that different cultures have very different social rules and expectations.

It looks to me that some “experts” in social skills for severe autism, or MR/ID, are giving some very bad advice.  It is worth checking what your child is being taught, to see if you actually agree with it.

I actually think Aspies have the most to benefit from social skills workshops outside school and coaching inside school, to find their niche in society.  If you get diagnosed with mild autism, you should automatically be enrolled.  Such workshops should be fun and not some kind of conversion therapy. 

Most children with autism want friends, they just don’t always know how to make them.  These are lifelong skills that you do not forget. 





Tuesday 15 December 2020

Fine tuning Social Behavior in Autism with an existing pediatric drug, Desmopressin?

 


There are two closely related hormones, vasopressin and oxytocin, that have been extensively researched in autism. 

With oxytocin you can modify social-bonding behavior. You can increase oxytocin in the brain either via a nasal spray containing oxytocin, or you can add a specific bacterium to your gut that triggers a signal to the brain to produce more of its own oxytocin.  The latter is my preferred method, because you can produce a mild long-lasting effect throughout the day.

Oxytocin has a very short life and it does not cross the blood brain barrier.

There is even a new study in the works that will compare these two methods of treating autism.

 

Probiotics and oxytocin nasal spray as neuro-social-behavioral interventions for patients with autism spectrum disorders: a pilot randomized controlled trial protocol

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication. Oxytocin (OXT), as a neuropeptide, plays a role in emotional and social behaviors. Lactobacillus reuteri (L. reuteri) supplementation led to an OXT-dependent behavioral improvement in ASD mouse models. Despite some promising results from animal studies, little is known about the efficacy of supplementation with L. reuteri, alone or with exogenous OXT therapy, on social-behavioral functions in ASD patients. This paper presents a protocol for a pilot randomized controlled trial to evaluate the feasibility of conducting a full trial comparing oral supplementation of L. reuteri probiotics and intranasal OXT spray to placebo on the effect of social and behavioral functions in ASD patients. The study will also capture preliminary estimates of the efficacy of the proposed interventions in ASD patients.

Methods

This pilot trial is a two-staged, randomized, double-blind, placebo-controlled, parallel-group study. Throughout the study (0–24 weeks), 60 patients with ASD will be randomly assigned to receive either oral L. reuteri probiotics or placebo. In the second study stage (13–24 weeks), all participants will receive intranasal OXT spray. As primary outcomes, serum OXT levels will be assayed and social behaviors will be assessed via the Autism Behavior Checklist and the Social Responsiveness Scale which are validated questionnaires, an objective emotional facial matching test, and a new video-based eye-tracking test. Secondary outcomes include the GI-severity-index and Bristol Stool Chart to assess GI function and gut microbiome/short-chain fatty acids. All the outcomes will be assessed at baseline and weeks 12 and 24.

Discussion

This pilot study will provide important information on the feasibility of recruitment, blinding and concealment, treatment administration, tolerability and adherence, specimen collection, outcome assessment, potential adverse effects, and the preliminary efficacy on both primary and secondary outcomes. If successful, this pilot study will inform a larger randomized controlled trial fully powered to examine the efficacies of oral L. reuteri probiotics and/or intranasal OXT spray on social-behavioral improvement in ASD patients. 

My conclusion was to add two drops of L.Reuteri DSM 17938 (Biogaia Protectis) into the liquid part of my son's Polypill therapy. That way there are no extra pills to swallow and in theory the bottle should last 50 days, so I am not forever looking to buy more.  If you want a bigger effect, just add more drops.  The producer suggests a daily dose of 5 drops for babies, to promote GI health - the original intended purpose.

When it comes to Vasopressin it looks like you cannot avoid a nasal inhaler, unless you want to try transcutaneous electrical acupoint stimulation (TEAS).  There is a debate as to whether Vasopressin and its analogs (man-made modified versions) can cross the blood brain barrier and to what extent. 

There are 4 previous posts that looked at Vasopressin. 

https://epiphanyasd.blogspot.com/search/label/Vasopressin 

The Vasopressin showing good results in the trials at Stanford is the injectable pharmaceutical version of the hormone made into a nasal spray.  This kind of spray could be made easily at a compounding pharmacy.

It turns out that a synthetic analog of vasopressin, called desmopressin, has been widely used for over 40 years to treat nocturnal enuresis (night-time bed-wetting) among other more serious conditions.

 

Desmopressin in Autism 

Nocturnal enuresis is common in individuals with but to our knowledge, there are no reports that desmopressin enhances social functioning in ASD (or in any other clinical population). This may be because desmopressin is typically administered at bedtime (so prosocial effects would be less evident) and orally (oral desmopressin does not cross the blood-brain barrier). The most likely explanation, however, is that desmopressin acts selectively on AVPR2, rather than on AVPR1A”

 

From:

A randomized placebo-controlled pilot trial shows that intranasal vasopressin improves social deficits in children with autism

 

Desmopressin N=1 example 

I was recently contacted by the father of a young boy with autism who has been prescribed Desmopressin nasal spray by his neurologist.

The father noted major positive behavioral changes from the first dose.

This is of course great news.

Desmopressin is a widely available drug, seen as safe, and that is why it is prescribed to children.

In the US the nasal spray version is no longer widely used for children and they use the oral version.

In some countries it is used for people with MS (Multiple Sclerosis) with nocturnal enuresis.

 

Desmopressin Shortage

Before readers get too excited, Ferring Pharmaceuticals, the big producer of Desmopressin nasal sprays did voluntarily withdraw its brands (Minirin, DDAVP Nasal Spray, Desmopressin Acetate Nasal Spray) from the market in August 2020 due to a quality problem. 


https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/ferring-us-issues-voluntary-nationwide-recall-ddavpr-nasal-spray-10-mcg01ml-desmopressin-acetate

  

There is now a shortage and so what was an easy to obtain drug, may be more difficult to get.  There is a Pfizer version called Presinex.  

From the above paper on vasopressin for autism:-

Vasopressin benefits 

“In conclusion, the present pilot study determined that 4-week intranasal AVP treatment compared to placebo enhanced social communication abilities, diminished anxiety symptoms, and reduced repetitive behaviors in children with ASD. On nearly all behavioral measures, participants with the highest pre-treatment blood AVP concentrations benefitted the most from AVP treatment, suggesting that pre-treatment blood AVP concentrations may be useful for setting dosing guidelines for this medication. Last, intranasal AVP treatment was well tolerated with minimal side effects in this pediatric study population. These preliminary findings suggest that intranasal AVP treatment has potential to enhance social abilities in an ASD patient population characterized by currently intractable social impairments” 

Transcutaneous electrical acupoint stimulation (TEAS) to raise vasopressin 

“there is evidence that nonpharmacological interventions may facilitate endogenous AVP release, for example, electroacupuncture stimulation increases brain AVP concentrations in rats. Transcutaneous electrical acupoint stimulation (TEAS) therapy improves social functioning and anxiety symptoms in children with ASD, particularly in those with the largest post-treatment increase in blood AVP concentrations. The authors of this prior report theorized that increased AVP signaling may be the mechanism by which the prosocial and anxiolytic benefits of TEAS treatment were achieved” 

 

Vasopressin with Bumetanide  - take great care

A while back, one reader did ask me about taking intranasal Vasopressin with Bumetanide.  His doctor in California thought this might not be wise since the two drugs have opposing effects.

·        Bumetanide (a diuretic) makes you pee more.

·        Vasopressin (the anti-diuretic hormone) makes you pee less.

The real problem is the risk of low sodium, hyponatremia.  This is always a risk with vasopressin and the risk might well increase if you took Bumetanide.  The risk is going to be dose dependent.

If you take Vasopressin and then drink large amounts of water this will disturb the volume of fluids in your body and in particular it will lower the level of sodium.  This may lead to seizures and ultimately worse.

Bumetanide does disturb the level of electrolytes, but nearly all the change usually occurs in Potassium, this is why you need to add back potassium via diet and add a supplement.  Sodium is not normally a problem, but always check all electrolytes when taking a blood draw.

If someone adds vasopressin to their existing bumetanide therapy, the doctor should definitely monitor the level of sodium.

In most people’s diet, sodium is one thing you are likely to have too much of and it is very easy to add a bit more sodium if the blood test suggests it is necessary.  In extreme cases of low sodium you need to use a special re-hydration drink, or an intravenous saline solution.  Monty has a relative who keeps going to hospital for the latter.

The diuretic action of Bumetanide is a side effect of the "autism effect" and so if you can reduce the diuresis of bumetanide that would be good thing.  Researchers are trying to find a better-bumetanide and their goal is to have no diuresis.

If combining vasopressin with Bumetanide is accompanied by both reduced diuresis and a matching reduction in fluid intake, this might actually work well.  Clearly, extra care needs to be taken and what might be perfectly safe in one person may not be safe in another person.

  

Conclusion

I do have to give a big thank-you to our reader who shared his experience with Desmopressin and to the neurologist for suggesting it.

Desmopressin looks like one of those autism therapies that needs only a very short trial to determine whether it is beneficial.  This is a big advantage.

You would hope the Stanford vasopressin researchers make a short trial of Desmopressin, just to compare the effect.  They probably will not.

All you have to decide is whether it is going to be the left nostril, or the right nostril.  With intranasal insulin there was a problem with irritation inside the nose, so alternating left and right sides might be best.  You hold your breath and then squirt the spray; the objective is not to breath the spray into your lungs.  An easy mistake to make.

Note that I am referring to the 10 mcg/0.1mL Desmopressin nasal spray.  The one used to treat kids that wet their bed at night.

There is also a much more potent 1.5 mg/mL version, called Stimate in the US.  This is used to treat von Willebrand’s Disease (Type I) and hemophilia/haemophilia.  You do not want that version.  This version is 15 times more potent than the anti bed-wetting variant. 

I have been suggesting to Aspies living in the US that they give Vasopressin a trial to counter the social deficits that some find troubling.  I think they are able to obtain this via a compounding pharmacy, with a helpful doctor’s prescription.

I think outside the US your doctor will think you are mad if you ask for a specially compounded vasopressin nasal spray, or indeed a compounded  oxytocin spray.

For people unable to get the intranasal vasopressin prescribed/compounded, Desmopressin is on option to discuss with your doctor. Maybe time to develop a bed wetting problem?

The Aspies in the Netherlands have the legal option of a tiny non-hallucinogenic dose of Psilocybin once a month, which seems an effective way to target Serotonin 5-HT2A receptor-mediated pathways and so improve social behavior. What caught my attention was that the effect of this tiny dose lasts a month and it can also be used to treat severe, otherwise untreatable, cluster headaches.

Psilocybin is the fancy name for magic mushrooms.

Psilocybin is also legal in Brazil and not surprisingly in Jamaica.  It looks like the US is moving in the same direction - medicinal magic mushrooms!


FDA grants Breakthrough Therapy Designation to Usona Institute's psilocybin program for major depressive disorder


The “medical” dose of Psilocybin is a tiny fraction of the “recreational” dose and is only taken when the effect of previous dose fades to zero.  It is not a crazy idea at all, just not currently a legal therapy in most countries.  More than half a century ago Lovaas was researching something very similar at UCLA, but using LSD.


All told, there are several potential ways to fine-tune social behavior in autism. Sulforaphane is yet another option.



 

Saturday 5 December 2020

Suramin in China, where things can move fast – blocking Enterovirus-71 rather than treating Autism

The new Chinese and old Colonial, side by side in central Shanghai

  

I do not speak Chinese, but fortunately Google does.

I was sent some interesting links to some articles from China about Suramin, the potential autism therapy which many autism parents are eagerly awaiting.  Prepare for a long wait, but hopefully less long in China.

My original post on Suramin for autism can be found  in the link below:-


Suramin, the Purinome and Autism

 

 

I have never had a banner appear on my computer trying to sell me a Rolls Royce until today.  This is more proof, if I needed it, of how much China has changed since my first visit there as a teenager.  Back then there were a lot of bicycles; I still remember many were Flying Pigeon brand – not a name you forget. I just looked them up and since 1950, more than 500 million Flying Pigeon bicycles have been made - that is a lot bicycles.

I even went to see a factory still producing steam locomotives in Datong in the 1980s. They gave you a personal certificate of your visit, which I still have somewhere. 

Last year I was again in China and travelled on their ultra-modern high speed trains.  These run on purpose-built tracks, often running to totally new vast railway stations.  The network is massive with 36,000 km (22,000 miles) in total length and trains running at speeds up to 220 mph / 350 km/h.  The ride is perfectly smooth and the tickets are not so expensive.   The old train lines I used many years ago still exist and you can still take the “hard sleeper” to travel long distances overnight for little money, but not quite as cheap as it once was.  

 


 Things move fast in China, hopefully so will Suramin

Suramin is an approved drug, but it is almost impossible to get hold of, unless you are in a limited number of African countries affected by African Sleeping Sickness and River Blindness.  Suramin is made by the German giant Bayer and the brand name (below) is not very original.

 



I think the clever idea is the intranasal version now being developed in the US.

But why not just put this old drug from 1916 in a metered pump dispenser, in the same way the Alzheimer’s researchers put insulin in a nasal spray?  In autism, Vasopressin and Oxytocin are just popped into nasal sprays.  A few years in this blog I mentioned Dr Jay Goldstein who was treating people with TRH intranasally (he wrote a great book called Tuning the Brain – I actually bought it).

Tuning the brain eventually got Jay Goldstein into trouble. Though long “retired”, he has just published another book on ME/CFS.  Goldstein also used Ketamine eye drops and nasal spray.

I guess if he would have been among the first put this old Suramin drug in a nasal spray and see what happens. It quite possibly would help ME/CFS, as suggested by Dr Naviaux himself.

We saw in a post in 2014 that Professor Rita Levi-Montalcini had the clever idea of using home-made NGF eye drops to stave off decline in old age.  She was the first one to discover the existence of Nerve Growth factor (NGF). She became the first Nobel laureate to reach the age of 100.  The NGF eye drops did not do her any harm.

Your eyes are part of the Central Nervous System (CNS) and so an ideal entry point to target the brain. For nasal sprays the route to the CNS is via the trigeminal nerves and not much actually gets through (see below).  Due to the blood brain barrier many drugs taken orally cannot reach the brain.

 

Nose-to-Brain Delivery

The route of transfer of compounds through the nasal respiratory epithelium to the brain is via the trigeminal nerves 

A key advantage of the nose-to-brain route is the possibility of reducing plasma exposure, as has been demonstrated thus eliminating peripheral side effects.

 Simply dissolving the drug molecule in an aqueous phase has been used to administer molecules via the nose-to-brain route. The vast majority of clinical studies, which report pharmacological effects, have involved a solution of the drug in aqueous media delivered using a nasal delivery device

Oxytocin has also been delivered to the brain via the nasal route using a solution with a Cmax of 0.003% of a 10 μg dose being found in the brain. A solution of the human immunodeficiency virus replication inhibitor DB213 delivered the drug to the rat brain with a Cmax that was estimated at no more than 0.007% of the administered dose.

The addition of functional excipients to these solution formulations improves brain delivery via the nasal route. 

 

It may well be that Rita and Jay got it right by choosing eye drops over a nasal spray. Suramin eye drops? Not as crazy as it may sound.  Perhaps in China?

   

Back to China

 For several years there has been research looking at treating hand foot and mouth disease using Suramin.

Hand, foot, and mouth disease is common in children under five years old, but anyone can get it.

The illness is usually not serious, but it is very contagious. It spreads quickly at schools and day care centres.

 

Hand, foot, and mouth disease is caused by viruses that belong to the Enterovirus family.

Common causes of hand, foot, and mouth disease are:

  • Coxsackievirus A16 is typically the most common cause of hand, foot, and mouth disease in the United States. Other coxsackieviruses can also cause the illness.
  • Coxsackievirus A6 can also cause HFMD and the symptoms may be more severe.
  • Enterovirus 71 (EV-A71) has been associated with cases and outbreaks in East and Southeast Asia. Although very rare, EV-A71 has been associated with more severe diseases, such as encephalitis. 


Enterovirus 71 (EV-A71)


Suramin inhibits EV71 infection

Highlights

·        Suramin inhibits the proliferation of EV71 virus.

·        Suramin directly blocks the attachment of EV71 virion to host cell.

·        Suramin can be used as a potential clinical therapeutic against EV71 infection.

 

Abstract

Enterovirus-71 (EV71) is one of the major causative reagents for hand-foot-and-mouth disease. In particular, EV71 causes severe central nervous system infections and leads to numerous dead cases. Although several inactivated whole-virus vaccines have entered in clinical trials, no antiviral agent has been provided for clinical therapy. In the present work, we screened our compound library and identified that suramin, which has been clinically used to treat variable diseases, could inhibit EV71 proliferation with an IC50 value of 40 μM. We further revealed that suramin could block the attachment of EV71 to host cells to regulate the early stage of EV71 infection, as well as affected other steps of EV71 life cycle. Our results are helpful to understand the mechanism for EV71 life cycle and provide a potential for the usage of an approved drug, suramin, as the antiviral against EV71 infection.

 

 

The approved pediatric drug suramin identified as a clinical candidate for the treatment of EV71 infection - Suramin inhibits EV71 infection in vitro and in vivo

 Enterovirus 71 (EV71) causes severe central nervous system infections, leading to cardiopulmonary complications and death in young children. There is an urgent unmet medical need for new pharmaceutical agents to control EV71 infections. Using a multidisciplinary approach, we found that the approved pediatric antiparasitic drug suramin blocked EV71 infectivity by a novel mechanism of action that involves binding of the naphtalentrisulonic acid group of suramin to the viral capsid. Moreover, we demonstrate that when suramin is used in vivo at doses equivalent to or lower than the highest dose already used in humans, it significantly decreased mortality in mice challenged with a lethal dose of EV71 and peak viral load in adult rhesus monkeys. Thus, suramin inhibits EV71 infection by neutralizing virus particles prior to cell attachment. Consequently, these findings identify suramin as a clinical candidate for further development as a therapeutic or prophylactic treatment for severe EV71 infection.

 

 

Kangzhi Pharmaceutical has the rights to develop Suramin for hand foot and mouth disease in China and beyond. 

 

Kangzhi Pharmaceutical has developed a new indication for "Suramin Sodium" and is committed to the development of drugs for hand, foot and mouth disease 


Currently, there are no specific antiviral drugs for enteroviruses in the world, and support and symptomatic treatment are the main ones. Clinically, there is an urgent need to develop specialized drugs to treat patients with hand, foot and mouth disease who have been infected. Now that Kangzhi Pharmaceutical's suramin sodium for injection has been approved for clinical trials, it is undoubtedly a gospel for children with hand-foot-mouth disease and is expected to break the dilemma of treatment of hand-foot-mouth disease.

Kangzhi Pharmaceutical has been focusing on children's health for a long time. Under the guidance of "Children's Health Strategy" and "Excellent Strategy", the company insists on investing about 5% of its annual sales in research and development. In 2013, the company took the lead in establishing a post-doctoral scientific research station with children's drug research and development as the main direction in China, and was recognized as "Hainan Children's Drug Preparation Engineering Technology Research Center" in 2016. In order to solve the problem of no medicine for hand, foot and mouth disease, Kangzhi Pharmaceutical has invested heavily in the research and development of suramin sodium for injection.  

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 For a long time, the anti-fever drug "Ruizhiqing (Nimesulide)" is Kangzhi Pharmaceutical's leading product in the children's medicine market. The company's revenue accounted for as high as 70% at one time. However, this product had previously suffered from side effects. Controversial, Kangzhi Pharmaceutical has no longer listed this product as a core competitive advantage in its financial report. Instead, it has given key exposure to another long-developed new drug for the treatment of hand, foot and mouth disease. ——Suramin Sodium for Injection.

It is understood that hand, foot and mouth disease is an infectious disease that is generally susceptible to infants and children under 5 years old. It continues to be prevalent at a fixed period every year. There is no specific medicine for targeted treatment. According to the statistics of the my country Center for Disease Control, the number of cases of hand, foot and mouth disease in China in 2018 was 2,533,310.

Obviously, if Kangzhi Pharmaceutical's new hand, foot and mouth disease drug can be successfully listed, it will become a major "cash cow" product of the company. By then, both performance and stock price will be effectively boosted. However, since this product was exposed by Kangzhi Pharmaceutical, the outside world only knows that this product will be "the world's first new medicine for the treatment of hand, foot and mouth disease", but its final market is still far away.

"The company has obtained the approval for the clinical trial of the drug, and the product has successfully completed the phase I clinical trial and will start the phase II clinical trial. If the clinical trial is successful and the marketing authorization is obtained, suramin sodium will become the world's first treatment for hand, foot and mouth. New medicine for disease.” In the 2019 financial report, Kangzhi Pharmaceutical introduced the latest development of suramin sodium.

As early as 2015, after Kangzhi Pharmaceuticals spent 18 million yuan to buy the patented technology of "Institutions and Methods for Treating Viral Diseases" of the Shanghai Pasteur Institute of the Chinese Academy of Sciences, and planned to invest 50 million yuan in suramin Subsequent research and development of sodium.

In 2018, after the application for the clinical trial of suramin sodium was submitted, it was quickly reviewed and approved according to the special review route. At that time, Hong Liping, vice chairman and vice president of Kangzhi Pharmaceuticals, said in an interview: "Suramin sodium for injection is approved for clinical trials, which is an important achievement of Kangzhi Pharmaceuticals in the development of new drugs. The company deeply feels the responsibility. With the help of the current national policy to encourage the spring breeze of clinically urgently needed therapeutic drugs, we will actively promote the development of clinical trials of the drug and promote the market of new drugs as soon as possible to help children with hand, foot and mouth disease get rid of the disease as soon as possible.

According to the company's secretary of the board of directors on the Shenzhen Stock Exchange, the clinical trial of suramin sodium is divided into 3 phases, and only phase 1 has been completed. The time of the clinical trial is uncertain.

It is reported that the new indication of suramin sodium for the treatment of hand, foot and mouth disease developed by Kangzhi Pharmaceutical has previously applied for an international invention patent through the PCT, and has successively obtained invention patent authorization in China, Japan, Singapore and the United States. The new Indonesian patent authorization will help to further leverage the advantages of independent intellectual property rights, promote the research of hand-foot-mouth disease treatment drugs, benefit the world's hand-foot-mouth disease patients, and enhance the core competitiveness of Kangzhi Pharmaceutical.

  

Conclusion 

It looks like there will eventually be at least 3 pharmaceutical companies selling Suramin.

  Bayer (Germany)

  Kangzhi Pharmaceutical (China)

  Paxmedica (USA), or really which ever Big Pharma they sell out to 

This is all good news for autism and hand foot and mouth disease. 

People do not like injections, nor side effects caused by your drug needlessly going everywhere in your body.

The nasal spray, or eye drops, look a good idea for autism and ME/CFS.

Hopefully the Chinese will move fast, like their trains, and bring their Suramin to the market.

 


In 2008 Arnold Schwarzenegger signed a bill to bring high speed rail to California.  The total system length would have been approximately 800 miles (1,300 km).  Where are we 12 years later?

The British are no better with their high-speed rail, but it is a very densely populated country. China's new rail lines were not built where the old lines ran. Spain actually has really good high-speed trains, that are not so expensive and a great way to get around the country.

Where are those autism drugs, "fast-tracked" for approval by the FDA? In the same place as Arnie’s model train set (going nowhere fast).