Bumetanide – Maths Test ✔✔✔ Clinical trial ✖✖✖
Memantine, Arbaclofen and now Bumetanide stumble in clinical trials
(also the less well known Balovaptan, which Roche dropped in 2020).
Place your bets on Suramin, anyone?
Plus ça change, plus c'est la même chose
The more things change, the more they stay the same
The first week of the school year brought two big surprises.
Monty, aged 18 with autism, came top of the class in the math test. This is a big win for bumetanide treatment, because 9 years ago Monty was effectivelyinnumerate. With a huge effort by his Assistant, he had learnt how to read and write, but even the most basic maths was beyond him. That all changed in 2012 thanks to Professor Ben-Ari’s published research on Bumetanide in autism.
The sad news that week was that the Phase 3 clinical trial of Bumetanide for autism had been terminated early.
Paris, 7 September 2021 – Servier and Neurochlore announce that no sign of effectiveness was observed in their two phase 3 clinical studies assessing bumetanide versus placebo in the treatment of Autism Spectrum Disorders (ASD) in children and adolescents. As a consequence, Servier and Neurochlore have decided, by mutual agreement, on an early termination of the two clinical studies in progress.
“The results of the phase 3 clinical studies are a major disappointment,” declares Professor Yehezkel Ben-Ari, President of Neurochlore. “Neurochlore’s teams will now analyze in detail the results of the studies and potentially explore new approaches based on artificial intelligence, which may enable us to identify sub-populations of people suffering from Autism Spectrum Disorders, for whom bumetanide could be effective.
Bumetanide also did not pass the NEMO clinical trial, as a treatment for neonatal seizures back in 2015. This then made it a bit awkward to suggest that children with severe autism might lower their risk of developing epilepsy by taking bumetanide. Since this is a blog, I can speculate. I would imagine children with severe autism, who are bumetanide-responders, and who are treated from early childhood through to adulthood with this drug, will have a low incidence of developing seizures. Seizures develop in about 30% of those with severe autism (DSM3 autism) and are the leading cause of their early death.
If such an effective therapy shows no benefit in a trial with 400 participants, something has gone seriously wrong.
I did ask one researcher friend, who just replied bluntly that the trial must have been poorly constructed. I thought that was a bit brutal, even by my standards.
Be honest and admit your limitations
Monty, aged 18, came top in maths among 15 neurotypical 16 year olds. But the 45 pupils in the year had been split into sub-groups. Two groups of 15 taking extended maths and one group of 15 taking core maths. For some reason, because Monty has autism they put him in the lower group.
Not to worry, after his coming top in the math test, the school agreed that he can move to one of the upper groups taking the wider math curriculum.
So Monty is no maths genius, he came top among the weakest group of typical kids. That is the whole truth, which is different to the partial truth.
In a similar way, autism researchers need to accept that there may never be a unifying therapy for autism, one that benefits everyone.
Concentrate on the responders to your treatment and forget the rest. If you over-sell your therapy, you will fail.
As I have said in this blog many times, most people with an autism diagnosis are not bumetanide-responders. However, a significant minority of those with severe autism are responders to bumetanide and they will experience a transformative benefit.
Going from a basket case to a Maths Whizz even?
Apply common sense and don’t outsource everything
In previous clinical trials of bumetanide, critics said it was all a placebo effect because the parents knew when they were giving bumetanide rather than a placebo. The bumetanide pill causes the diuresis and placebo does not.
Why can you not use a different diuretic as the placebo? Answer that one!
Many people using bumetanide give up because of the diuresis. With schoolkids, the parents will receive complaints from school about excessive toilet breaks. There will be wetting of trousers, car seats etc. There will be anxiety caused by urgently needing a toilet, when none is nearby.
So you need a strategy in advance of how to deal with the diuresis.
I was told that people in the one trial centre I know about, were told nothing about the diuresis and how to cope with it. I was even told the clinician basically told the parents that it was a stupid trial. Not a good way to ensure compliance with the trial protocol.
So what happens? Some parents will decide to stop giving the diuretic drug, at least on school days. Maybe they think that a “double-dose” at the weekend will make up the difference.
Clinical trials are a business these days and are outsourced to companies that do this and nothing else. Don't outsource the most critical part of your work, or at least supervise it.
Why, oh why, oh why?
I was contacted by a mother from the southern hemisphere who managed to get Bumetanide prescribed by a pediatrician, based on Ben-Ari's earlier publications. The diuresis is proving a problem for her family, but the positive effects are clear, for example her son now uses the word “Mummy”, but only while taking Bumetanide. If you are a Mum/Mom, that is a big deal. He also now responds to his own name and is "more present", the hallmark sign of a bumetanide-responder.
She saw me on YouTube and sent me a long email, including the “why, oh why, oh why?” are more people not giving bumetanide to their child with severe autism. There is no good answer.
This Mum, now realizing she is not alone, plans to continue Bumetanide therapy.
Good for her!
Who dares wins, or at least stands a chance
I was recently sent an email version of an old post I had written on myelination. The sender had read it and convinced her doctor to prescribe her son Clemastine.
Her son has a single gene autism that is known to feature impaired myelination.
I pointed out that in my blog there are many references to therapies shown to benefit different aspects of the myelination process, clemastine is just one. Some of these therapies are OTC, like alpha lipoic acid (ALA) and theN-Acetyl glucosamine (NAG), that Tyler brought to everyone’s attention.
Is the young man in question going to improve in function taking one or all of these 3 therapies? At least the mother in question is going to give them all a good shot.
Good for her.
Conclusion
I have received quite a few comments and messages about the Bumetanide trial failure. Many are along the lines of “what do we do now?” and “how long will we have to wait?”
It looks like it pays to be an early adopter, rather than having faith that clinical trials will be structured and implemented properly.
It has been suggested in the research that a large, 10g, daily dose of the OTC supplement TMG (trimethylglycine) may have an equivalent chloride lowering effect to bumetanide. There is only anecdotal evidence to support this, but it seems to work for our reader Nancy's adult son - good job Nancy! The other potentially chloride lowering drugs are more difficult to obtain than bumetanide itself.
There likely will never be a single unifying therapy for autism, just like there can never be for cancer. In both conditions it is all about specific sub-types.
You would think that the previous trial failures in autism would have caused people to learn this important lesson.
Hopefully, in the future Suramin clinical trials, where two competing companies are using the same therapy, it will not be assumed that everyone must be a responder for the therapy to be valid. From the data, it does look like Suramin improves symptoms in a significant percentage of those with severe autism; but the same can also be said of Bumetanide, based on the earlier trials
In December Monty will commence his 10th year of Bumetanide therapy. We have made short breaks periodically to check it is still needed. For our case of autism, Professor Ben-Ari clearly got the science right and transformed a little boy's future life, something Ben-Ari can always be proud of.
Comments
Post a Comment