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Thursday, 2 April 2015

Treating autism with a diuretic: a long procedure


Several readers have asked me about the current status of Bumetanide as a treatment for autism. The process in Europe is controlled by EMA (European Medicines Agency), the equivalent of the FDA in the United States.  

Bumetanide affects the function of the GABAreceptor.  If you click on the site index, you can refer to Bumetanide and read the research and my own son's very positive experience of using this drug since December 2012.     

Most readers in the UK and USA have difficulty getting their doctor to prescribe bumetanide, since autism is currently an off-label use.  Many readers elsewhere have been able to access this drug and are seeing its positive impact.

Dr Ben-Ari, whose research has been outlined in those earlier posts, has kindly provided this update:-




Treating autism with a diuretic: a long procedure 


We have started some time ago testing the possibility of using a diuretic to treat Autism Spectrum Disorders (ASD) relying on our promising experimental observations made in rodent. Indeed we discovered in 2 animal models of ASD (the in utero Valproate model and the Fragile X one) that cortical neurons have elevated intracellular chloride that shifts a major inhibitory mechanism to excitatory leading to perturbations of the behaviorally relevant brain oscillations (Tyzio et al Science 2014 and Eftekhari et al Science 2014). Correcting these elevated levels of chloride with a diuretic that reduces intracellular chloride ameliorated the electrical and behavioral signatures of ASD in these rodents. Relying on these and indirect observations, we had conducted with Dr Lemonnier a pilot trial followed by a phase 2 randomized double blind placebo control study on 54 children aged 3 to 11yrs old. We obtained promising results (Lemonnier et al Trans Psychiat 2012). Thus is followed now by a larger EMA approved trial with 80 children 2 to 18 yrs old that will be terminated next fall.

The procedure is long and complex as this requires many clinical controls and large sums of investments. This is however mandatory as  one cannot propose a treatment unless this has been tested and approved by the clinical authorities. Indeed, there have been many false hopes in the treatment of ASD, and one cannot give false promises without having all the elements needed that confirm that the treatment does improve the situation and has limited or no side effects.

We cannot therefore make any suggestion and promise as to the success or failure of the approach in spite of our compelling animal data and preliminary clinical observations. We follow the requirements and when and if our trials are successful , we shall pursue until we obtain an authorization to market this drug.

Sincerely


Information is available at






17 comments:

  1. Peter,

    When Dr Ben-Ari says the study will be "terminated", does that mean it will cease to continue because of some issue? Or, does it mean it will conclude as scheduled?

    Also, does he mean fall 2015 or fall 2016?

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    1. I was informed that they are now completing the 80 person trial in France, this is the EMA approved trial. So I suppose it must be Fall 2015. (terminated just means completed, not "dead and buried")

      This is then followed by a trial in several European countries, to confirm the result; in fact some of these trials have already begun.

      There is an article in French here:-

      http://www.asperansa.org/actu/questions_e_lemonnier.html

      You can use Google translate to put it into English.

      I expect the trial will show that in about 50% of cases, there is a significant to profound improvement. People with autism second to mitochondrial disease do not benefit, and I expect various other phenotypes. The people with the core classic autism do seem to benefit.

      But it is just a start, there are other dysfunctions remaining. Hence why I have this blog.

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  2. Hi Peter, I have found your recent posts about cognitive enhancements convincing and actionable. One question (and you may have addressed this), but what interventions in your polypill has best reduced obsessional behavior? Thank you v much

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    1. To reduce obsessive behavior/stereotypy/stimming I am using NAC (N-acetylcysteine). This was also the subject of a clinical trial at Stanford.

      A good place to start is 2,400 mg of NAC split into three daily does (eg 1,200mg , 600 mg and 600 mg). The effect increases with the dosage, but then tails off.

      NAC does taste bad. A more expensive version that tastes good is available, called Pharmanac in the US and Fluimucil in Europe.

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  3. Unfortunately, Pharmanac is out of stock in every site I've checked. A few sites say it might be available again in early April.

    Peter- thanks for the excellent blog. I just started biotin for my 8-year old autistic son per your recent posts- it's unlikely to help, but easy to try. Thankfully, amazon has a strawberry-flavored pill (5mg) that dissolves easily in the mouth.

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  4. It would be interesting to know what they plan to do if the phase 2 data is positive. If it is, it may be extremely lucrative and hopefully someone with sufficient capital can push through the phase 3 trials and marketing authorisations. Interestingly, i act (as corporate lawyer) for a number of pharma and biotechs who are redirecting drugs and/or clinical trials towards autism (particularly channelopathy related, especially starting with schizophrenia). They are also reinvesting generally into neuroscience

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  5. Bumetanide is already available as a cheap generic drug. They are just re-purposing an old drug, so they will not make big money. I think the current trial is phase 3, so they have nearly finished. In the US the process is more involved and so they are just going for approval in Europe. A doctor in the US can then just prescribe off label, noting the approved use in Europe.

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    1. thats good to know. We're in the UK but are going to the US to see an ASD specialist doctor over the summer. I'll add that to the long list of stuff available in the US but not in the UK

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  6. I think they can make good money if they turn bumetanide into a drug that targets the brain more effectively. Let's hope they succeed. That will also be of great benefit to users, not getting low blood pressure, hypo kal, or visiting the bathroom 20 times a day.

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  7. @ Peter -

    My son is 2 yeard old and is under Biomedical Intervention under the guidance of nutritionist (with vitamin, probiotics supplements). Since starting Biomedical intervention - my son has shown promising improvements for ASD.
    Like Improvements in Speech, better eye contact, less hyperactivity, better sleep at night.

    Though my son is making good progress, I am also keen to try Bumetanidebut but want to do this under the guidance of a Paeditrician, do you know any MAPS doctor in UK to get specifc guidance for this?

    regards,
    Deepak.

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    Replies
    1. Hi Deepak, there are no MAPS doctors in the UK but there might be some neary, as in Europe. Try to attend the autism conference taking place in London, June this year, where Dr Lemonnier will be presenting on bumetanide potential for autism.

      http://treatingautism.org.uk/event/the-treating-autism-international-conference-2016/

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    2. Thanks Natasa, I have already booked tickets and I am looking forward to hear Dr Lemonnier

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  8. If there are no MAPS doctors in the UK, can some one point me to a private paeditrician who treats ASD and prescribes medecines (wither in UK or Europe), I am keen to try leucovorin (folinic acid) but it looks like I need a prescription for this.

    I have also send my son's blood sample to http://iliadneuro.com/lab_tests and awaiting the results.
    This is for Folate receptor antobodi test.

    So trying to get in touch with a paeditrician and get an appointment before the test results come in.

    regards,
    Deepak.

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  9. Peter, Thank you for all the information. In India bumetanide has been stopped. But lasix (furosemide) is available. It is mentioned that 40 mg lasix is equal to 1 mg bumetanide. Will it be as effective as bumetanide? What about potassium depletion with lasix? Also only 600 mg Fluimicil tablets are available. They can be cut in to two? What is the approximate dosage of fluimucil for a two year old child? Thank you.

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    1. Furosemide affects both NKCC1 and KCC2, so it may be less effective than bumetanide, but it may be better than nothing. You would have to try it. It will deplete potassium. Fluimucil can be split in half. I would try about 1.5g a day split in three or four doses.

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  10. I am wondering if anyone knows if the conference proceedings from 2016 conference are available anywhere to purchase/view, thank you.

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    1. Some of them are available, you can enquire and request them by writing to mail@treatingautism.org.uk

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