Bumetanide and/or low-dose Clonazepam for Autism




Today’s post answers a question left un-answered in earlier posts about the best way to treat the imbalance (excitatory vs inhibitory or just E/I) that exists in the function of the key neurotransmitter GABA in many types of autism.

I first started this blog after the pleasant shock of seeing the positive behavioral and cognitive effect caused by Bumetanide.

This was just copying a recent French clinical trial on humans.

Later on in this blog we came across Professor Catterall who made two experiments in mice to show that the same E/I imbalance could be treated using tiny doses of a drug called Clonazepam.  At doses a hundred time higher, Clonazepam is used to treat seizures and anxiety, but at those doses it dose have side effects.

The mechanism is different to Bumetanide, by the effect was claimed to be the same.

Since Bumetanide has actually been shown effective in a human trial, most readers of this blog have this as their first choice.

I commented that in Monty, aged 11 with ASD, there was indeed an additional positive effect of adding clonazepam to existing bumetanide therapy.  Now having several effective treatments, it is harder to quantify the effect of new ones.  

It remained unknown what would be  the effect of low dose Clonazepam without the Bumetanide. 

Since Bumetanide is known to reduce potassium levels, albeit in a minority of cases, to the extent that supplementation is required, it is necessary to monitor blood levels of potassium.  This is a drawback of the therapy, although the majority of people will not actually need supplementation.  So one regular reader of this blog has tried Clonazepam; and I assume, Maja, without Bumetanide.

Here is her feedback.


Tried Clonazepam 0.025mg in one dose, in the evening, before sleep. After whole 3 days, as you predicted, change was amazing - she become self confident, a bit naughty, but in some joyful, playful way. Started to play more often with friends (by report of teacher end assistant in school). They both reported that she is different, but in good way, even she is harder to manage with (i didn't tell them about new therapy in that time)

Started to play differently, not in pattern she's developed over the years (she has great imaginations, wich is a plus, but has stereotype of ideas in the play).

First of all, we noticed that she is capable to sense odors (she had some kind of anosmia before), than she managed to catch a rhythm to dance (that was a real wow!).

She was speaking with people in the shop (briefly, but adequately)...
There is much more...

Change is still present, but after three weeks are slightly paler . There are not so intense. I'm still overwhelmed, just wont to know if I am missing something.


Thank you Maja for sharing.

In Monty, the effect was not this profound, but then he was already on Bumetanide, and so I was rather expecting no effect.


So, bumetanide and/or low-dose clonazepam for Autism?  

I suggest both, for maximum effect.





P.S.  For the scientists among you

There is another drug, Diamox/Acetazolamide, that I think may also have the same effect as Bumetanide and Low dose Clonazepam.  It is a so-called carbonic anhydrase inhibitor, meaning it forces the kidneys to excrete bicarbonate (HCO3-) and thus makes the blood more acidic.  This has the side benefit of increasing the amount of oxygen in the blood, and hence its use off-label to prevent altitude sickness.  In the brain this change in HCO3- should affect Anion exchanger 3 (AE3) and Sodium dependent anion exchanger (NDAE) which sit alongside the GABAa receptors. By reducing Cl- levels within the cell, the effect would be the same as Bumetanide, which affects the NKCC1 transporter.  This might explain why Diamox, a diuretic, is also used to treat some epilepsy and periodic paralysis.  Note Bumetanide is also used to treat periodic paralysis and some seizures.

This was all covered in a very complicated post:-
GABA A Receptors in Autism – How and Why to Modulate Them

If you are one of those who believe that there is mild hypoxia in some cases of autism, then you could also consider Diamox as an alternative to hyperbaric oxygen therapy.
  










  



Comments

Post a Comment

Popular posts from this blog

mTOR – Indirect inhibition, the Holy Grail for Life Extension and Perhaps Some Autism

Image
  Not cheap at about $1,000 for just 140mg Life extension may come as a surprise, but it is interesting because it is well studied and, in mice at least, easy to measure.  Most research into mTOR relates to cancer, but this is a very complex condition. With various feedback loops it means that sometimes the actual effect is the opposite of what was predicted.  For example, a substance that can help prevent cancer can actually become harmful later and promote its growth. Direct inhibition of mTOR with Everolimus and similar drugs (variants/analogs of Rapamycin , all called Rapalogs) has not been as successful as hoped in cancer research.  Trials of direct inhibition of mTOR will shortly start in one rare single gene type of autism ( TSC ).  The drugs are so expensive that many providers do not want to pay for them. As you will see mTOR is just one process in a cloud of interrelated processes.   Almost everything has a role/effect:- growth factors, cytokines,...
Read more

Zinc, Hedgehog Signaling, Shank2/3, NMDA/AMPA Inactivation and Autism

Image
I am gradually tying up the loose ends in this blog. Today several issues are dealt with that are all connected by zinc. Some are extremely complicated and I will skip over the details. Not that kind of hedgehog 1.      In those rather complicated graphics in the literature that explain signaling pathways, you may have noticed something called hedgehog signaling. This is a basic pathway present in all bilaterians - creatures with a head and tail/feet and a left and right. So flies, yes; but jelly fish, no.   In autism there is excessive hedgehog signaling.   Zinc deficiency is linked to activation of the hedgehog signaling pathway 2.      One of the commonly used models of autism is called Shank3; there is another one called Shank2.   Shank proteins are scaffold proteins that connect neurotransmitter receptors and ion channels to the actin cytoskeleton and G-protein-coupled signaling pathways.   Mutations in these genes are ass...
Read more

Bravo Monty! Academic results in Autism

Image
  Some risks are worth taking, however long the journey Academic results are part of most people’s life, whether you love them or loathe them. Most children diagnosed today with autism will do just fine at school, but this was not always the case.   Those born 20 or 30 years ago and diagnosed in early childhood with autism are usually in a much less fortunate position. Today’s post is about level 3 autism and what the Lancet Commission want to call Profound autism. The new idea is that if by age of 8, a child with autism still has severe intellectual disability or minimal language then he/she can be best described as having Profound Autism. In other literature the term SDA (Strictly Defined Autism) was proposed.   I t means what was called autism back in the 1990s and earlier. You can have severe autism with any level of IQ, which I think many people may not be aware of, or even accept.   Monty and his Academic Results The “bravo” for Monty comes from Dr Ben-A...
Read more