It will soon be 10 years that I have been offering this treatment for children with autism spectrum disorders with my friend Eric Lemonnier. Including our 2 successful inaugural phase 2 clinical trials, 7 other trials have been carried out around the world with, according to a meta-analysis, more than 1036 children successfully treated (Xiao et al). This is without counting the numerous pilot tests. This recent Egyptian phase 2 study (Shaker et al) is interesting because it compared numerous evaluation criteria and not only the average criterion chosen as the pivot. 99 children aged 3-12 years were recruited, half receiving the placebo and the other half receiving treatment with the usual dose – 0.5mg x 2 times a day. They observed a statistically significant improvement (between treated and placebo) in numerous criteria, including adaptation to change, emotions, sharing and socialization, sensory responses, etc. For other criteria, there are no significant effects.
In agreement with this hypothesis, our large phase 3 trial (covering more than 420 children recruited in 40 centers in Europe, Brazil and Australia) failed. Its success required obtaining significant differences between treated and placebo children on a scale – here the CARS – with a significant difference. It should be remembered that no phase 3 trial for the treatment of autism (or more genetic forms such as fragile X) confirms that the same molecule will not be able to treat all forms of autism. As a result, we decided to re-examine all subscales in phase 3. Using an AI approach, we can identify subpopulations of children responding to Bumetanide relying on clinical subscales. In short, this means that the phase 3 trial has failed but not the treatment that we are recommending, which could alleviate autism in a subpopulation of children.
Clearly, the development of a treatment for autism will require identifying more homogeneous subpopulations likely to respond to treatment, and this is what I am focusing my efforts on from now on. Unfortunately, it is impossible for me at this stage to determine when this work will be completed, because I must validate these results in a large trial focused on children with the properties that we have identified and therefore possible responders. This requires raising of substantial financial resources, which is far from obvious in the current circumstances, with pharmaceutical companies favoring new and profitable treatments rather than repositioned, generic molecules.
Finally, let us highlight an interesting study which shows that bumetanide has positive effects on an animal model of Fragile X in keeping with a pilot trial we have conducted (Kourdougli et al).
Shaker E, El Agami O and Salamah A, Bumetanide, a diuretic that can help children with autism spectrum disorders – 2024, CNS Neurological Disorders Drug Targets; (4) 536-542
Xiao, H.L., et al. (2024) Can bumetanide be a miraculous medicine for autism spectrum disorder: Meta-analysis evidence from randomized controlled trials. Research in Autism Spectrum Disorders 114, 13
Nazim Kourdougli, Toshihiro Nomura, Michelle Wu, Anouk Heuvelmans, Zoë Dobler,
Anis Contractor, Carlos Portera-Cailliau (2024). The NKCC1 inhibitor bumetanide restores cortical feedforward inhibition and lessen sensory hypersensitivity in early postnatal fragile X mice.
