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“Down to the brass tacks” of getting optogenetics into the clinic

Soon after bioengineer Karl Deisseroth, MD, PhD, first developed a way of controlling neurons using light, researchers started employing the technique (called optogenetics) to understand diseases of the brain.

Another group of researchers realized that optogenetics held potential beyond the brain: in the spinal cord, in the nerves that control movement or signal pain, and in organs and tissues that use electrical signals to secrete hormones or carry out other functions.

In that time, I’ve lost count of the number of stories I’ve written describing scientific advances based on optogenetics. Each exciting. Many hinting at future therapies. None about a clinical trial.

In April, Deisseroth wrote a review in Cell addressing what has been learned from optogenetics studies in the brain and describing a possible path to the clinic. Meanwhile, a group led by bioengineer Scott Delp, PhD, wrote a parallel article in Science Translational Medicine laying out the path to therapies for the rest of the body, called the peripheral nervous system. His lab has done work on the nerves that detect pain and that control muscles.

I spoke with Shrivats Iyer, one of Delp’s graduate students, about the review. (Kate Montgomery, a former graduate student, was also a lead author on the paper). He pointed out that some barriers for using optogenetics to treat diseases of the brain and the periphery are similar. In both cases, any therapy would require getting certain light-sensitive proteins into the relevant neurons. That involves gene therapy, which is a field that has its own set of issues. In addition to challenges of safely employing gene therapy, those new genes could cause an immune reaction in the peripheral tissues (the brain is largely protected from these immune responses).

"This issue of immune response is a grand challenge for gene therapy more broadly," Iyer told me.

Then there’s the light. For diseases of the brain, getting a light source deep into the brain to where the relevant neurons are located requires poking holes through some tissues that I, for one, would rather keep intact. I have enough trouble remembering things or balancing without holes poked in my brain. Deisseroth does point to new techniques using LED light and wireless power that could overcome these issues.

In the rest of the body, an additional issue is movement. The brain is nicely isolated inside a stable skull. Nerves in the arm or abdomen, not so much. Iyer told me, “The broad problem is now you have these complex dynamic structures that normally flex and bend and whatever light delivery system you use has to flex with that.”

The Delp lab and others have worked on creating flexible cuffs that go around limbs to deliver light, and Stanford engineer Ada Poon, PhD, has created a wireless way of delivering light for optogenetics.

“A significant amount of the proof of concept work has been done,” Iyer told me. “Now the field is down to the brass tacks of how we get this into the clinic.”

Previously: Miniature wireless device aids pain studiesUsing optogenetics to build a biological pacemaker and Optogenetics: Offering new insights into brain disorders

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