As a notorious night owl, it was already very early in the morning of October 5 when Karl Deisseroth, M.D., Ph.D., finally laid down to get some shuteye. Not long after, the phone of the Stanford psychiatrist and bioengineer lit up with an incoming call from Sweden.
“I was in a not fully conscious state, so I didn't answer it,” Deisseroth recalled to Fierce the next day.
“But they called my wife, who was next to me, and asked her to give me the phone,” he said. “I took the call on her phone, and they told me that I'd been awarded the Nobel Prize in Physiology or Medicine.”
Though the call came in the dark, Deisseroth’s prize—which he shared with German scientists Peter Hegemann, Ph.D., and Georg Nagel, Ph.D.—is all about light. The trio were awarded for their pioneering work in optogenetics, a technique where neurons are engineered to become sensitive to light. By then beaming lasers into the brain, usually of mice or rats, the specific function of neurons and brain regions can be deduced.
As a basic research tool, optogenetics has fundamentally reshaped neuroscience. But for Deisseroth, the point was always to ultimately have a clinical impact.
Control of specific neurons “is a goal of not only basic science but also clinical neuroscience,” he told Fierce. “As a psychiatrist, I've delivered electroconvulsive therapy to many patients and seen that it's effective. But it has side effects. It's certainly not as precise as we'd like.”
Deisseroth co-founded MapLight Therapeutics in 2018 to harness optogenetics for neuroscience drug discovery, and the biotech is now gearing up for phase 3 trials of candidates in schizophrenia and autism-related irritability. But the clinical use of optogenetics likely to cross the finish line first is much more direct.
The same light-sensitive proteins—originally sourced from a species of algae—that Deisseroth embedded into rodent neurons two decades ago can also be inserted into human nerve cells. The result is a gene therapy approach that is close to becoming a reality for the many patients suffering from retina-related vision loss diseases.
Experts who spoke with Fierce agreed that this niche field, once primarily occupied by Novartis but now also the domain of a small set of biotechs, should see a big boost thanks to the recognition this week.
“The Nobel Prize is wonderful news,” said José-Alain Sahel, M.D., a French ophthalmologist and early optogenetic gene therapy pioneer who directs the Vision Institute at the University of Pittsburgh School of Medicine. “It does illustrate where the field is heading and what we can do if good science is being promoted.”
Gazing into the pond
The story of optogenetics opens with Peter Hegemann’s interest in a species of green algae called Chlamydomonas reinhardtii. These single-celled photosynthesizers can detect and move towards light, and Hegemann was determined to figure out how they do it.
Hegemann, together with ion channel expert Georg Nagel, ultimately puzzled out that the algae use a unique type of light-activated switch to trigger movement. When exposed to the right wavelength, the protein—called channelrhodopsin—opens and allows ions to flood through.
After reading the duo’s key papers in 2002 and 2003, it was clear to Deisseroth that expressing the gene for rhodopsin in mammal neurons could be a way to make them controllable using light. Neuron activity is normally mediated by other kinds of ion channels that are activated by electric charge.
Still, there were “many reasons to think it wouldn't work,” Deisseroth said. Algae and mammals are separated by about a billion years of evolution; channelrhodopsin in algae requires another compound, known as a cofactor, to work properly; and, at the time, forcing genes into cells was not as easy as it is today.
Nevertheless, while trialing a suite of potential methods for activating neurons, Deisseroth decided to give channelrhodopsin the old college try.
“Amazingly, totally unexpectedly, it was this high-risk experiment that actually worked the best,” Deisseroth said.
With optogenetics off the ground, another far-fetched idea wasn’t far behind. In 2010, Deisseroth and colleagues—including ophthalmologist Sahel—stuck a bacterial rhodopsin into retinas from human cadavers and saw they reactivated photoreceptors.
That finding ultimately led to the 2012 creation of Parisian biotech GenSight Biologics, where Sahel serves on the board of directors. Before moving to Pittsburgh, Sahel founded and was director of the Vision Institute in Paris, which GenSight spun out of.
The approach of GenSight and other optogenetics outfits is to use viral vectors to deliver genes for a channelrhodopsin, to bestow light-sensing abilities to cells that otherwise don’t respond to the sun’s rays. This way, some degree of vision can be restored even if all the normal photorecepting cells have been lost, and no matter what the cause of the disease is.
The field’s highest level of pre-Nobel hype came in 2021, when Sahel and colleagues published findings from one patient with retinitis pigmentosa. By combining a gene therapy for a red-sensitive channelrhodopsin with a special pair of goggles that projects light into the eyes, the blind patient was able to perceive and touch objects.
In a nice bit of timing, GenSight followed up on Wednesday with further data from a phase 1/2 study of 10 patients, six of whom saw clinically meaningful increases in light sensitivity.
The data mean “we could start the phase 3 in one year or two years,” GenSight CEO Laurence Rodriguez told Fierce. “It will be the last step of a long journey, but we are not so far.”
But if GenSight is knocking on the door, another biotech has already cracked it open. Texas-based Nanoscope Therapeutics has an optogenetic therapy, called Mogenry, sitting in front of regulators in the U.S. and Japan. Unlike GenSight’s approach, Mogenry doesn’t require any special device to activate light sensitivity.
Mogenry delivers a construct of three different proteins into the eye, Nanoscope co-founder and Chief Scientific Officer Samarendra Mohanty, Ph.D., told Fierce. “It's a very complex protein, and we were concerned that this will create [an] immune reaction,” he explained. So far, the therapy has proven safe.
Nanoscope published data from four patients in 2025, and last month presented four-year follow-up data from its phase 2b/3 trial in retinitis pigmentosa at the Annual Scientific Meeting of the Retina Society.
The work of Sahel and GenSight advanced the field and generated excitement, Mohanty conceded, but the required goggles are “cumbersome” and he’s concerned about potential toxicity from beaming light into patients’ eyes.
“We want to avoid intense light in the eye because it causes damage,” he explained.
Toxicity is something that still needs to be thoroughly investigated, GenSight's Rodriguez told Fierce. Efforts to minimize the goggles are underway.
“You have to manage carefully the wavelengths and the timing of exposure,” the CEO said. The regulatory path for a treatment that combines gene therapy and a non-invasive medical device “is not really clear.”
“It's two different dossiers, but at the end a connected dossier,” she said of the regulatory filings. “It will be a new pathway.”
Nanoscope's Mohanty expects the FDA to make a decision on Mogenry in the first half of next year, and the biotech has already begun building up its commercial team and planning more clinical trials in other retinal diseases. But the company has a direct competitor in the non-goggle optogenetics space: the Berkeley-based startup Ray Therapeutics.
Ray CEO Paul Bresge touted to Fierce his company’s finely tuned protein product, built from the work of Zhuo-Hua Pan, Ph.D., another early optogenetics pioneer who founded the Allergan-acquired RetroSense Therapeutics. With Allergan—now part of AbbVie—no longer pursuing optogenetics, Pan kept working to refine his tech.
“We've taken the most light-sensitive protein that's found in nature, and then we've highly bioengineered it for human vision restoration,” Bresge explained.
Ray is the biggest money-raiser in the field, having brought in a $125 million series B earlier this year. Mohanty, though, isn’t worried about the potential challenge to Nanoscope's Mogenry.
“You can raise a ton of money and buy all the power in the marketplace, but I do not see them as competitors,” he told Fierce. “To be very honest, they have not started their randomized controlled trial.”
Bresge told Fierce that a phase 2/3 trial in retinitis pigmentosa is in the works, and Ray has already launched a phase 1/2 open-label trial in Stargardt disease.
The Ray CEO got interested in optogenetics after his daughter was diagnosed with retinitis pigmentosa just after turning 15. He left his prior company, jCyte, in 2020 and co-founded Ray in February 2021.
“I was just like, okay, this is where I'm going to hang my hat,” he told Fierce. “We're not disclosing the data. What I can tell you is we are absolutely blown away with what we're seeing in change of visual field.”
Today, Bresge’s daughter is a 30-year-old artist and writer “doing everything that the doctor told her not to do,” he said. “She's remarkable.”
For Sahel, it doesn't really matter which company or optogenetics approach ultimately prevails. What's important is making progress for patients.
“Avoiding the goggles is probably a good thing if it works because it's less bulky, it's less inconvenient for the patient,” Sahel said. “Anything that works for the patient is great.”
Right now, traditional vision loss gene therapies from Beacon Therapeutics and others only work when given early in the disease and for specific mutations. Optogenetics, should it pan out, can service those who have already lost all their vision, and is agnostic to the biology driving the disease.
“Each can have a specific role in the landscape,” Sahel said. “We are making a lot of progress in optogenetics, so it may work at earlier stages of the disease. But still it's a palliative therapy. It's not a curative therapy.”
Unlocking the brain
While the first-ever optogenetics therapy may clear the FDA as early as next year, Nobel-winner Deisseroth told Fierce he thinks the biggest impact of the light switch approach will come through what it illuminates about the brain.
“I think an even bigger opportunity—and this is what led to MapLight—is what we call indirect optogenetics,” he explained. “The process is to first determine which cell types are causal in disease symptoms or in symptom resolution, and then using that to build medications.”
In other words, instead of activating or inhibiting certain neurons using light, optogenetics is used as a research tool to uncover which cells are responsible for a given disease. Then, those cells can be hit with traditional drug types.
“Being able to stand on that bedrock of causality, and then looking for medications, was the key principle for MapLight,” he said.
The biotech recently posted a mixed phase 2 readout for its schizophrenia prospect, an M1/M4 muscarinic agonist called ML-007C-MA, and elected to halt all preclinical work to drill down on the drug. The biotech’s autism candidate ML-004 also stumbled this summer, failing to meet the primary endpoint of a phase 2 trial.
Still, both drugs are progressing to phase 3, Deisseroth said, and the fact that the first candidates produced by MapLight’s optogenetics approach are for schizophrenia and autism is both “surprising and gratifying.”
“I was led to psychiatry through a chance encounter on a psychiatry ward during med school with a schizoaffective disorder patient,” he told Fierce. “I ended up treating autism as one of my main patient populations. But I wouldn't have necessarily picked either autism or schizophrenia to be initial targets.”
Deisseroth is rooting for companies that are working on direct optogenetics for vision loss, but ultimately said that their reach will be naturally limited to the eye.
Indirect optogenetics, on the other hand, “could apply to basically every neuropsychiatric condition,” the newly minted Nobel Laureate said. “There's no gene therapy, there's no device, it's all building medicines through that pathway. It's so much more generalizable.”
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