Enhancing the effect of Bumetanide in Autism
Many readers of this blog, and some of those who leave comments, are using the Bumetanide therapy proposed by Ben-Ari and Lemonnier.
At some point it should become an approved autism drug and Ben Ari has already patented it for use in Down Syndrome, so I guess that will come later on.
I have been developing my own add-on therapies that might help people for whom a high level of intracellular chloride is part of their autism, or indeed Down Sydrome. If Bumetanide has a profound impact on your autism, this is almost certainly you.
Monty, aged 13 with ASD
After 4 years of Bumetanide, it continues to be effective and if Monty stops taking it there is a gradual cognitive decline over a few days, presumably as chloride concentration gradually increases.
In spite of an odd temporary Tourette’s type verbal tic that developed after an infection before Christmas, I have been getting plenty of feedback that Monty has got cleverer in 2017. So it looks like some bumetanide add-on does indeed work.
Monty’s big brother continues to be a fan of Lego and indeed Nanoblocks from Japan. Nanoblocks is like extremely small Lego.
Having completed the Colossuem, his latest Nanoblocks model, he asked Monty “where is it?”.
Back came the answer, unprompted, “Italy”.
This was a big surprise.
That was not the answer big brother expected, he expected no answer or a silly answer like “over there”.
Add-ons
The first is potassium bromide (KBr) which was the original epilepsy therapy 150 years ago. One of its effects is that the bromide (Br-) part competes with chloride (Cl-) to enter neurons and bromide is known to be faster. As a result some of the chloride inside cells is replaced by bromide. Bromide is extremely similar to chloride, but is not reactive; this is why it can be used with any anti-epileptic drug (AED) without fear of negative interactions.
KBr has an extremely long half-life, meaning that if you take it every day it will take 4-6 weeks to reach its stable level in your body.
KBr is used for pediatric epilepsy in Germany and Austria and for epilepsy in pet dogs all over the world.
A dose of 8mg/kg is far below the dose used for epilepsy, but does have a bumetanide enhancing effect in one 50kg boy.
The even more recent add-on is based on the experience of our reader Petra’s son with Asperger’s, who found that taking his bumetanide with Greek coffee seemed to make it more effective.
It turns out that dopamine is known to increase the effect of diuretics on the chloride cotransport NKCC2 in your kidneys. There is a myth that coffee is a diuretic, but it is clear where this myth has come from. Coffee will increase diuresis and so does caffeine.
In the brain it is the chloride cotransporter NKCC1 that is also blocked by bumetanide. So it would be plausible that dopamine/coffee/caffeine it might have the same effect on NKCC1 as it does on the very similar NKCC2.
The cheap and widely available 50mg caffeine tablets do seem to serve as a proxy for a steaming cup of Greek coffee. Indeed 50mg of caffeine is more like a weak cup of instant coffee.
I did much earlier propose the use of Diamox/ Acetazolamide to reduce chloride. It seems that in some neurons 2/3 of the chloride enters via NKCC1 and 1/3 via the exchanger AE3. Diamox/ Acetazolamide works via AE3.
Diamox has some other ion channel effects, making it useful in some epilepsy.
Some readers of this blog use Diamox, but in Monty it seems to cause reflux.
Caffeine is a very simple add-on to try.
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