• Optogenetics, which uses light to control nerve cells at the individual level, has been shown to restore sight in clinical trials.
• Researchers said it can be used to learn more about neurological disorders.

The Nobel Prize in Physiology or Medicine has been awarded to three scientists involved with pioneering research into optogenetics, the study of how nerve cells shape feelings and behaviors in the living brain.

The scientists include Karl Deisseroth, PhD, MD, a physician-scientist with Stanford University and investigator with the Howard Hughes Medical Institute; Peter Hegemann, PhD, Hertie senior professor of neuroscience at Humboldt University in Berlin; and Georg Nagel, PhD, professor of molecular plant physiology at the University of Würzberg, Germany, according to a press release.

Optogenetics serves primarily as an engine for discovery, offering a general approach to understanding which cells matter in normal function and dysfunction, as well as which cells can correct symptoms, Deisseroth told Healio.

“It can be applied to almost anything,” he said. “The research is really exciting because it’s so general. We can now start to think about the entire brain as a dynamical system. How does activity flow across the brain?”

The Nobel Prize was awarded to recognize research that officials with the Nobel Assembly said fundamentally alters the understanding of the brain.

“Optogenetics provides opportunities for mapping the brain in a way that we could once only dream of,” Per Svenningsson, chair of the Nobel Committee for Physiology or Medicine, said in the release.

Hegemann’s research in the early 1990s into the microscopic alga Chlamydomonas was the catalyst for optogenetics. His work led to the discovery that the algae could sense light through an eyespot and react in half a millisecond, faster than the human eye processes light.

Hegemann hypothesized that a single protein in the alga was responsible for both capturing light and acting as an ion channel.

Hegemann and Nagel teamed up to research the proteins, including channelrhodopsin-2, confirming Hegemann’s hypothesis.

The duo introduced the gene for channelrhodopsin-2 into embryonic human kidney cells, and the cells began to produce an electrical signal when exposed to light.

Separately, Deisseroth was searching for a protein that could be used to trigger electrical impulses in nerve cells as part of a broader effort to better understand how the human brain functions. He and his colleagues obtained DNA from Nagel and introduced it to rat nerve cells, which began to produce channelrhodopsin-2.

Deisseroth’s discovery unlocked the potential for controlling nerve cells in live animals using blue light, which allows researchers to see exactly which cells control different brain functions, including those tied to pain, social behaviors and attention, among others.

Optogenetics has several indications that are advancing, Deisseroth said. Direct optogenetics involves putting a light-activated ion channel into people and is being used in clinical settings to restore vision in people with retinitis pigmentosa, he said.

Indirect optogenetics, which involves finding cells that are relevant in causing or correcting symptoms, has a much larger application domain, according to Deisseroth. Its use can potentially lead to designing medications that would address those cells.

The second phase of two trials grounded in indirect optogenetics, one into autism and one into schizophrenia, have been completed, Deisseroth said.

“The key point is that it’s grounded in, for the first time, something we have wanted for a long time in psychiatry: true cellular causality understanding for the symptoms,” he said.

Optogenetics offers a fundamentally different approach to vision restoration, said Lejla Vajzovic, MD, FASRS, director of the Duke Surgical Vitreoretinal Fellowship Program.

“Rather than rescuing photoreceptors that have already been lost, we can potentially make surviving retinal cells light-sensitive and create a new pathway for visual information,” Vajzovic told Healio.

In a phase 3 trial, optogenetic therapy demonstrated clinically meaningful improvements in visual acuity, Healio previously reported. The company behind the research, Nanoscope Therapeutics, is seeking FDA approval.

The trial met its clinical endpoint for improving sight in patients with ultra-low vision, said Vinit Mahajan, MD, PhD, professor of ophthalmology and vice chair for research in the department of ophthalmology at Stanford University. Mahajan was also a co-author on Nanoscope’s phase 1 trial.

Optogenetics are particularly relevant in ophthalmology because people need light-sensitive cells to see, Mahajan told Healio.

“You're using the power of molecular biology to re-engineer [the proteins] to do what you want them to do and then packaging them into a gene therapy virus to carry them and target the cells,” he said. “It's a technological triumph.”

The combination of the Nobel Prize recognition and the FDA potentially granting approval to the first optogenetic therapy designed for human use make this an exciting moment in science, he said.

“Ophthalmology is setting the precedent for the rest of medicine,” he said. “This is a big step for bioengineering in general. The impact is not just optogenetics going into humans. To me it’s what we can do with synthetic bioengineered proteins to make people healthy.”

Vajzovic said she is excited about the potential of optogenetics to be mutation-agnostic, meaning that a single approach could potentially benefit patients with many different causes of retinal degeneration.

“Moving forward, we need to improve the quality and resolution of restored vision, optimize light sensitivity and, most importantly, demonstrate meaningful improvements in patients’ everyday lives,” she said.

There is also hope optogenetics can eventually lead to treatments for a wide range of mental health disorders, HHMI officials said in a press release.

“Optogenetics has enabled scientists to control the activity of neurons, providing vital new insights into brain function,” Leslie Vosshall, HHMI vice president and chief scientific officer, said in the release.

Karl Deisseroth, PhD, MD, can be reached at neurology@healio.com.

Lejla Vajzovic, MD, FASRS, can be reached at lejla.vajzovic@gmail.com.

Vinit Mahajan, MD, PhD, can be reached at mahajanv@stanford.edu.