Stopping seizures with light
Optogenetics is an experimental technique that uses weakened viruses to incorporate light-sensitive proteins into neurons. These proteins – known as opsins – are usually ion channels, and their role is to transport specific metal ions into and out of neurons, creating an electrical current (in this case known as a photocurrent because it is triggered by light). Opsins can be stimulated or blocked using different frequencies of light (usually blue or green), and by shining the appropriate light onto treated neurons, scientists are able to control their activity and learn more about their functions. One clinical aim of this is to develop a device that detects an oncoming seizure very early and emits light to silence the affected neurons. However this would require implanting a light source into the brain – an invasive and complicated process – and it is not clear how an implant would affect brain function. Finding a less invasive approach would be much preferable.
The discovery of ‘Jaws’
In previous work, engineers led by Professor Ed Boyden, at the Massachusetts Institute of Technology, identified two opsins that that are stimulated by light in the red spectrum. Red light can penetrate tissue further than blue or green, so the team was keen to find out if this would allow them to a) control neurons from further away and b) influence a larger volume of tissue at once. When they tested the opsins, however, they found that the photocurrent they generated was not strong enough to be useful in controlling neuronal activity.
In the current study, graduate student Amy Chuong and colleagues set out to improve the photocurrent by searching for relatives of these opsins and testing their electrical activity. They then created mutants to obtain an opsin with the most optimal properties. When the mutants were screened the team discovered one that they later named ‘Jaws’, which retained its red light sensitivity but also had an adequate photocurrent.
Working with Jaws
The group has already used Jaws to successfully shut down neuronal activity in a rodent brain with a light source outside the head. The suppression occurred as deep as 3 millimetres in the brain, and it was just as effective as that achieved using the invasive method. Human skulls are a lot thicker than rodent skulls of course, and so if this were applied clinically the light source would not be outside the head – the light simply wouldn’t reach far enough. Moreover there would be a risk of interference from light outdoors. However, it might be sufficient to place the light source on the surface of the brain rather than within it, which would require a much less invasive procedure.
A lot more research is needed before this technique can be applied to humans. There are not just questions about whether or not it will work; the potential risks aren’t yet understood either. However if in time it is deemed clinically suitable, and an appropriate device is developed, it could potentially revolutionise the treatment of epilepsy and other neurological conditions.
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