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Tuesday, 10 September 2013

Bumetanide in Autism and Epilepsy – Drug Licensing Status

In Europe, drugs have to be licensed by the European Medicines Agency, or each country’s national drug’s agency.  In the US ,the regulatory body is the Food & Drug Administration (FDA).

Drug approval is a slow and costly process and results in different drugs being available in different countries, or the same drug being licensed for different age groups or illnesses in different countries.

Bumetanide has been licensed around the world for many years for use in adults.

 
Bumetanide

Bumetanide is a loop diuretic originally licensed more than 30 years ago to treat heart failure.  It has a secondary function; in the brain bumetanide blocks the NKCC1 cation-chloride co-transporter, and thus decreases internal chloride concentration in neurons. In turn, this concentration change affects the action of the neurotransmitter GABA, which has been shown to be useful for treatment of neonatal seizures, that quite often are not responsive to traditional GABA-targeted treatment. Bumetanide is therefore currently under evaluation as a prospective antiepileptic drug.

Bumetanide is also being investigated by a French researcher, Dr Ben-Ari, for use in treating childhood autism.

Bumetanide was developed with older patients in mind and was never licensed for children, let alone babies.  Experimentally, Bumetanide has been used in babies for many years.


Bumetanide in Neonatal Seizures – NEMO project

You may have read in earlier posts about the research done using bumetanide to treat neonatal seizures.  There is now a 15 strong consortium including Duke University in the US, Great Ormond Street Hospital in the UK and Dr Ben-Ari’s INMED in Marseille, who have joined forces to bring this therapy to the market. The initiative is called the NEMO project and they have a slick website explaining their work.

The clinical trials are being carried out at 7 sites across 5 European countries.  The phase 1 study has been completed.

The objective is to develop a bumetanide formulation for neonatal seizures and obtain a drug license called a Paediatric Use Marketing Authorization (PUMA), from the European Medicines Agency.  The drug can then be prescribed to babies within Europe.

 
Bumetanide in Autism

Dr Ben-Ari is soon to conduct a phase 2 clinical trial of the use of bumetanide for autism in multiple European centres.  This study follows on from the already completed initial studies in France.

Some parents, mainly in France, are already using bumetanide for their children with ASD.  Most others clearly want the drug to fully certified for use in childhood autism before trying it, or are unable to obtain it, since it is a prescription only medicine.

Dr Ben-Ari informed me that he expects his bumetanide formulation is likely to be licensed for prescription in Europe to autistic children within four years’ time.

The FDA has more onerous (costly) requirements than its European counterpart and so the drug will only be licensed in Europe as a therapy for childhood ASD.




 

8 comments:

  1. Very encouraging article - when you have a child with both Autism and Epilepsy - as I do ....... :o )

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  2. Note that a recently published comprehensive review on the use of bumetanide in the treatment of neonatal seizures indicates that theres is no evidence to support the use of this drug in the treatment of central nervous system disorders via the NKCC1-dependent mechanism described above, as at the very low doses that are given to infants and children bumetanide does not reach sufficient levels in the brain.

    direct link to the original review:
    http://onlinelibrary.wiley.com/doi/10.1111/epi.12620/pdf

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  3. Thanks for this. There may be better drugs that cross the BBB more freely in the future. As the paper states at the moment Bumetanide is the only such drug available. I can tell you that in a 33 kg child with autism, 1mg of Bumetanide is potent enough to cross the BBB and affect the excitatory/inhibitory behavior of GABA. In some other children it has no such effect.

    I have no direct experience of neonatal seizures, but if Bumetanide can cross the BBB in autistic children, it probably can do in babies. There is a great deal of research currently taking place regarding bumetanide and neonatal seizures. Those researchers might well dispute the findings of your paper.

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    1. Your claim ("potent enough to cross the BBB") is based on what? The fact that you see CNS effects, does not mean that the primary site of action of a drug is the CNS.

      Your statement "I can tell you that in a 33 kg child with autism, 1mg of Bumetanide is potent enough to cross the BBB and affect the excitatory/inhibitory behavior of GABA." is for sure not based on scientific evidence.

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    2. If you want to doubt the science, then go and argue with Yehezkel Ben-Ari, who is the scientist proposing Bumetanide for Autism, rather than the person using it.

      I just read the research and then trial what I believe looks plausible. I made a trial of Bumetanide and it did exactly what Ben-Ari claimed. For me that is all evidence I need. 1 mg does the job required in a 33 kg child, for some reason that displeases you. Maybe people in Finland are different.

      If Ben Ari has got the mechanism all wrong, which is unlikely, I do not care. What matters is whether it works. If you want to argue why it works, go write to Ben Ari, but not as Mr Anonymous

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  4. Peter, Bumetanide has had a huge impact on my son's cognitive skills.
    It has given back his laser focus ability to deal with advanced mathematics and physics. He can't get enough of it.
    Also, unless there is an allergy, or something to that effect, so far he seems meltdown free.
    I just don't know what to say...doctors can give different kinds of antidepressants, anxiolytics, neuroleptics, but they can't prescribe Bumetanide?

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    1. Petra, that is great to hear. I thought it would have less effect in Asperger's, maybe in your son he just has a small dysfunction and so it is a case of "fine tuning", whereas in Classic autism the dysfunction causes a more profound cognitive impairment.

      Anyway, it is great that it works. Tell your biotin researcher doctor and also see if it helps your nephew.

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  5. Petra, also if one of your doctors will give you a prescription you will find it easy to acquire in another country. In Germany they will happily dispense against a prescription from another country, even a supply for one year. You could buy from an "official" online pharmacy in the UK (so no customs duty or VAT). If it is not available in Macedonia or Bulgaria, you can buy it very cheaply in Serbia and, with a prescription, if you ask for 40 packs they will just order it and have it the next day, all for less than 100 euros.

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