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August 12 Treats autism with reduced sensitivity of peripheral sensory nerves

Autism spectrum (ASD) drug treatment is being developed, but there are high hurdles to using drugs that have an effect on the brain during development. For example, the effect of Bumetanide on ASD symptoms has been confirmed, but it has been found to compete with various side effects.

On the other hand, the symptoms of ASD are largely due to secondary effects caused by hypersensitivity to input from the outside world, and the theory has emerged that treatment may be possible by changing the sensitivity of peripheral nerves, not the brain. It was. A paper from Harvard University introduced today was published in the August 8 issue of Cell, a study that thoroughly pursued this possibility, although it was an animal model. The title is “Targeting Peripheral Somatosensory Neurons to Improve Tactile-Related Phenotypes in ASD Models”.

Although the work is enormous, the direction of the research is clear, and the aim is to show that ASD can be induced and treated by manipulating it so that changes in sensitivity occur only in the peripheral sensory nerves, not in the brain.

To that end, we first conducted an experiment to introduce Shank3 and Mecp2 genetic mutations that cause ASD only into peripheral sensory nerves, and showed that various ASD-like social behaviors were induced simply by increasing the sensitivity of peripheral sensory nerves. Yes. In addition, this reverse experiment shows that normalizing genetic mutations in ASD model mice due to genetic mutations only with peripheral nerves improves ASD-like symptoms in parallel with the return of somatic sensation. .

Next, we conducted experiments to induce peripheral sensory nerve mutations at different developmental stages. When mutations were induced after 28 days, sensory nerve function was impaired, but ASD symptoms did not appear. It has been shown that ASD symptoms occur when mutagenesis is induced from, and surprisingly that anxiety behavior decreases when mutagenesis is induced from the 10th day of life. That is, it shows that the change in somatosensory changes the brain network according to the development period.

One of the causes of abnormalities in many ASD models is thought to be hypersensitive nerve excitement caused by decreased GABA inhibitory nerve activity. Therefore, in order to increase GABA responsiveness in peripheral nerves, we will conduct experiments to introduce GABARB3 specifically for peripheral nerves and confirm that ASD symptoms can be improved by normalizing GABA nerve activity.

Finally, we conducted experiments in which GABA receptor stimulators that cannot cross the brain-blood barrier were administered to various genetic ASD model mice for 6 weeks after birth to normalize various social behaviors. Indicates that treatment is not possible.

The above results show that ASD symptoms can be improved by targeting only peripheral nerves, and that it is possible to do so only by stimulating GABA receptors regardless of the cause. Personally, it was also interesting that the effects of peripheral nerve abnormalities on brain network formation differed so much depending on the developmental stage. I think research is particularly important in cases where both deficiency and hypertrophy induce similar symptoms, such as MECP2.

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