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Showing posts from January, 2017

The Purkinje-RORa-Estradiol-Neuroligin-KCC2 axis in Autism

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Add testosterone/estradiol to those dysfunctional hormones This blog is about noticing connections and making things a little simpler to understand.   Today’s post is going to be a good example; all those odd sounding things like Purkinje cells and neuroligins all fitting nicely together. Today we see how a central hormonal dysfunction (testosterone/estradiol) can lead to an ion channel dysfunction (NKCC1/KCC2) at one end of the chain and at the other explains the absence of many Purkinje cells in the autistic cerebellum, which leads to some of the observed features of autism. I am calling it the Purkinje-RORa-Estradiol-Neuroligin-KCC2 axis, or Purkinje-KCC2 axis for short. We also get to see how melatonin fits in here and see why disturbed sleeping patterns should be expected in someone affected by the Purkinje- KCC2 axis. I should point out that not everyone with autism is likely affected by the Purkinje-NKCC1 axis, but I think it will apply to a majority of those with non-regre...

The Clever Ketogenic Diet for some Autism

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I have covered the Ketogenic Diet (KD) in earlier posts.   There are more and more studies being published that apply the KD to mouse models of autism. Calling the KD a diet does rather under sell it.   The classic therapeutic ketogenic diet was developed for treatment of pediatric epilepsy in the 1920s and was widely used into the next decade, but its popularity waned with the introduction of effective epilepsy drugs. There are various exclusion diets put forward to treat different medical conditions; some are medically accepted but most are not, but that does not mean they do not benefit at least some people. When it comes to the ketogenic diet (KD) the situation is completely different, this diet is supposed to be started in hospital and maintained under occasional medical guidance. The KD was developed as a medical therapy to treat pediatric epilepsy.   It is very restrictive which is why it is used mainly in children, since they usually will (eventually) eat wh...

Tideglusib, Repairing  Dental Cavities, Wnt signaling, GSK-3 and Autism

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Kings College in London seem to be more effective in dentistry than autism; they have just published research showing how they effectively regrew a tooth to repair a cavity.   That is rather clever. Perhaps soon to be a thing of the past? Using biodegradable collagen sponges to deliver the treatment, the team applied low doses of small molecule glycogen synthase kinase (GSK-3) inhibitors to the tooth. They found that the sponge degraded over time and that new dentine replaced it, leading to a complete, natural repair. Natural tooth repair method, using Alzheimer's drug, could revolutionise dental treatments The full paper is here:-   Promotion of natural tooth repair by small molecule GSK3 antagonists All very well, but what has this got to do with Autism? As regular readers will be aware, autism turns out to be multigenic (it involves lots of different genes) and no single gene seems to account for more than one or two percent of cases.   A small number of any ...

Enhancing the effect of Bumetanide in Autism

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Many readers of this blog, and some of those who leave comments, are using the Bumetanide therapy proposed by Ben-Ari and Lemonnier. At some point it should become an approved autism drug and Ben Ari has already patented it for use in Down Syndrome , so I guess that will come later on. I have been developing my own add-on therapies that might help people for whom a high level of intracellular chloride is part of their autism, or indeed Down Sydrome.   If Bumetanide has a profound impact on your autism, this is almost certainly you. Monty, aged 13 with ASD After 4 years of Bumetanide, it continues to be effective and if Monty stops taking it there is a gradual cognitive decline over a few days, presumably as chloride concentration gradually increases. In spite of an odd temporary Tourette’s type verbal tic that developed after an infection before Christmas, I have been getting plenty of feedback that Monty has got cleverer in 2017.   So it looks like some bumetanide add-o...