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Optogenetics shows promise in curing neurological illness

05 Feb 2016  | Carolyn Mathas

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The field of neurosciences is now looking at light in a different way. Aimed at the treatment of chronic pain and other neurological disorders, the on-off switches of optogenetics are paving the way for novel methods of treatment.

So far used in lab animals such as mice, a wireless signal activates LEDs located near an animal's spinal cord so that a blue light turns on genetically modified neurons, while a yellow light turns them off. This enables researchers to discover the brain paths involved in such conditions as obsessive-compulsive disorder (OCD) as well as depression.

Inserting the LEDs near the spine of mice, however, is a bit different than in their human counterparts. The procedure involves the genetic engineering of neurons so that molecular switches that activate and deactivate cells can occur and an optical fibre would need to be placed in the brain to trigger the switches.

Stanford University researchers led by Karl Deisseroth formed Circuit Therapeutics, founded in 2010 to treat neurological diseases. The company hopes to begin clinical trials for the treatment of chronic pain, which will not be as invasive as the depression and OCD trials of the future since neurons affected by chronic pain are accessible and located on the outside of the spinal cord rather than the brain. Other treatments under development at Circuit Therapeutics include those for Parkinson's and other neurological disorders.

RetroSense Therapeutics, another optogenetics company in Michigan, plans to conduct human trials for a genetic condition causing blindness by using an ion channel made up of proteins that conduct neurons' electrical signaling. While neurons contain hundreds of different types of ion channels, opsins derived from algae and other organisms open in response to light. Channel rhodopsins, the first opsins used in optogenetics, open to allow positively charged ions to enter the cell when activated by a flash of blue light, so that the neuron fires an electrical impulse. Other opsin proteins can silence neurons.

The main challenge before optogenetic therapies become a reality is getting opsin genes into adult human neurons. With mice, this is done invasively; mice are either bred specifically to make opsins in neurons or a virus is used to implant a gene into the neuron. These viruses have to be able to penetrate mature neurons and deliver genes without causing an immune reaction.

So far researchers have successfully relieved pain in mice by activating opsins to shut down the pain-producing circuit. The opsins are in neurons on the skin and when the skin is illuminated, painful touch and heat sensitivity is successfully suppressed. There's no doubt the procedure will be attempted in humans but there's no assurance of success at this point. In humans, light delivery to the brain would require major surgery for some disorders. Pain, however, might be alleviated simply with a light-emitting patch or a wireless implantable device.

Challenges include the activation of neurons with light, as the patients are not necessarily still. There is also the potential for nerve tissue damage with the use of light.

The technology is yet in its infancy. For those experiencing severe depression and diseases like Parkinson's, however, turning this light on can't come soon enough.




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