Sunday, 5 January 2014

Long Term Bumetanide Use in Autism

This blog started life after I read about a clinical trial of the diuretic bumetanide to treat autism.  In the following 12 months the authors of that study, Ben-Ari and Lemmonier, have been busy building up their scientific case.  They published two further papers:-
We report that daily administration of the diuretic NKCC1 chloride co-transporter, bumetanide, reduces the severity of autism in a 10-year-old Fragile X boy using CARS, ADOS, ABC, RDEG and RRB before and after treatment. In keeping with extensive clinical use of this diuretic, the only side effect was a small hypokalaemia. A double-blind clinical trial is warranted to test the efficacy of bumetanide in FRX.

This single case report showed an improvement of the scores of each test used after 3 months of treatment. Double-blind clinical trials are warranted to test the efficacy of bumetanide in FRX.
Clinical observations have shown that GABA-acting benzodiazepines exert  paradoxical excitatory effects in autism, suggesting elevated intracellular chloride (Cl-)i and excitatory action of GABA. In a previous double-blind randomized study, we have shown that the diuretic NKCC1 chloride importer  antagonist bumetanide, that decreases (Cl-)i and reinforces GABAergic  inhibition, reduces the severity of autism symptoms. Here, we report results from an open-label trial pilot study in which we used functional magnetic  esonance imaging and neuropsychological testing to determine the effects of 10 months bumetanide treatment in adolescents and young adults with autism. We show that bumetanide treatment improves emotion recognition and  enhances the activation of  brain regions involved in social and emotional perception during the perception of emotional faces. The improvement of emotion processing by bumetanide reinforces the usefulness of bumetanide as a promising treatment to improve social interactions in autism.
My experience after 12 months of Bumetanide
Bumetanide continues to have a positive effect on Monty, aged 10 with ASD, which I would summarize as a marked increase in awareness or “presence” or a lack of “absence” from the world.  Improved social interactions may have followed, but are secondary.

My own impression is that the effect peaks and then reduces somewhat.  This also appears to be the case with NAC and Atorvastatin.  I think the body is adjusting to the new treatments, via feedback loops.  This is inevitable, it is just a matter of human physiology.  If the above MRI study shows a long term change in brain function, then great.
I hope that my future therapies will be more disease changing, this does look to be possible.  Early signs are promising. 

My experience of 12 months blogging
My doctor mother asked me over Christmas how many people have been reading my blog and acting on it.  The answer is about 6,000 page views a month, but I suspect less than 10 people have even tried Bumetanide, nobody has tried Atorvastatin, and a few tens have tried NAC.

I think people are frightened of drugs.  Supplements are OK and any kind of unusual diet is great.
I think if I proposed a diet of baked beans, fried eggs and bacon I would have a much bigger following. Luckily that was not my objective.

With the advent of the internet, simple drugs like diuretics are as easy to buy as supplements like NAC; I doubt you are going to get into trouble for having an unauthorized diuretic in the bathroom cabinet.
Supplements are not subject to the same manufacturing standards as drugs and there are pretty strange things sold as “supplements”.

I will continue to develop my own therapy for classic early onset autism and when I finish, I will patent it and produce it as an orphan drug.  Orphan drugs are for rare diseases, where there is no other treatment.  They have less daunting regulatory requirements, meaning you do not need $25 million to develop them. In the EU you need a serious condition affecting fewer than 5 in 10,000 people; across the EU that equates to 250,000 people.  If you narrowly define my target autism phenotype, with biomarkers you end up within this limit.
Unfortunately, if you want to patent something, you have to keep it secret.  I did discuss all this with the venture capital firm that commercializes the intellectual property of my old university plus that of Cambridge, Oxford and UCL. The conclusion was to either give it to the world for free, or to commercialize it.  Giving it for free clearly has zero impact, so it has to be Plan B.

So the blog continues, but it will not contain all the clever stuff.

Next steps
I have also been busy in the last twelve months, having taken my inspiration from the Frenchmen, Ben-Ari and Lemmonier.  I have had my own “breakthroughs”, by applying the research and some imagination.

While you cannot totally cure genuine autism, you can go a long way, far further than I would have dared to believe possible.
You can treat the most difficult issues such as absence, anxiety, aggression and SIB.  Odd behavioural traits like obsessions and compulsions can be greatly reduced.  The combined effect is definitely a much happier person.

I think there is much more possible in areas like mood, confidence, creativity, sociability and indeed cognitive performance.
Bumetanide was a very important first step, but in itself it is far from a “cure”.  In combination with some other safe drugs, the result will indeed be remarkable.
The final element will be time itself.  The human brain does not come ready programmed; the first few years of childhood are used to establish full brain function.  In autism, during these important first few years the brain was running in “safe mode”, all sorts of important connections were never made and some were lost.  The brain does remain plastic throughout life and so it has the potential to make some of these missing connections.
The drug treatment has to deal with oxidative stress, neuro-inflammation, several ion channel/transporter dysfunctions and the tricky area of central hormonal hypofunction/dysfunction.

Note that not all people with autism respond to Bumetanide. Only a large clinical trial will show what percentage are responders.  In the same way, I expect only a minority of those diagnosed with ASD by current psychiatric measures will respond to my drug; but it would be possible to identify them based on biomarkers and case histories. 



  1. We will be trying verpamil, even tho our dev ped said no. I'll let ya know how it goes- buying it from Canada

    1. It is likely to work if there is some visible problems with allergy (eg food or pollen). So if there are GI problems or rhinitis, it may be very helpful.


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