The following transcript has been edited for clarity

Hi, I'm Samarendra Mohanty, PhD, cofounder, president, and chief scientific officer of Nanoscope Therapeutics. I’m here to talk about the history and origin of the optogenetic technology, which we are advancing to treat patients with severe vision loss due to different inherited retinal dystrophies as well as geographic atrophy.

Retinal Physician: What first led you to explore optogenetics as a way to restore vision in patients with retinitis pigmentosa?

Dr. Mohanty: I was introduced to retinitis pigmentosa by a neuro-ophthalmologist at UC Irvine, which sparked my interest in restoring vision in these patients because there was no treatment option then, and there still isn't one.

When the photoreceptors are lost, one approach was to stimulate the remaining cells, such as bipolar or ganglion cells, using electrical circuits. Although that had given some hope and vision to patients, it was nowhere near the normal vision that patients would like to have to substantially improve their quality of life.

And that's when optogenetics emerged, around 2006. Most optogenetic approaches at that time were primarily used to probe neural circuitry by stimulating cells with a single wavelength or color of light. At that time, as a biophysicist, it came to my mind: How can we broaden the activation spectrum of these opsins so that patients can see without requiring an external device?

Retinal Physician: Was MCO-010 designed from the beginning to work in ambient light without goggles or other external devices?

Dr. Mohanty: From the beginning, I started working from a patient-centric view: What would a patient like to have? Something that would allow them to act in a normal environment, where the light intensity is much lower. So the idea was to fuse different opsins. They may not all function as ion channels, but they are light-sensitive molecules that together can enhance the conversion of light into electrical signals.

The second consideration was how to broaden the activation spectrum so that patients could see whether they’re in a blue-light environment, green light, red light, or even white light. And all this without compromising the kinetics because, as you know, vision is a very dynamic process. So whether an object is moving or the person is moving, one should not see blurring because of the temporal kinetics of the opsins.

Those are competing factors, so much of my research over the past decade has focused on optimizing this by fusing 3 different proteins from 3 different organisms. These are nonmammalian organisms, and the proteins must work in synchrony to achieve the desired target product profile. We also had to work toward engineering a proprietary AAV vector that could package this large 3-opsin fusion complex into a single AAV vector and deliver it to bipolar cells, which are abundant and preserved in these low-vision patients.

Retinal Physician: When did you realize your laboratory research had the potential to become a treatment for patients?

Dr. Mohanty: After years of experimentation, we optimized all the unique properties of sensitivity, broadband spectrum, and kinetics using patch-clamp electrophysiology, which is a standard technique in neuroscience laboratories. But when we injected the therapy into animals, especially mice, and placed them in a radial water maze under very low ambient light levels—dimmer than the bright light we have here now—we could see that the mice were able to find the platform without making any errors. So that really showed us that this technology could work in patients without requiring goggles or amplifying the light, even in an ambient lighting environment.

Retinal Physician: What have you learned from patients treated with MCO-010 that you couldn’t have learned from preclinical research?

Dr. Mohanty: We learned a lot, even though the technology was designed very well. As I said, we didn’t even imagine whether this would only improve light sensitivity or also improve visual acuity. We conducted certain experiments in mice, but most of these animal disease models lack a fovea, the area with a high concentration of photoreceptors that provides sharp visual acuity. And we weren’t expecting the results we saw in our phase 1/2 trial, where 7 of 8 patients improved by more than 3 lines of vision. That was really something we never thought of achieving.

And very recently, we’ve also seen improvements in color vision across all 3 trials, which is not something we anticipated. We’ve recorded these improvements using the National Eye Institute Visual Function Questionnaire (NEI VFQ), specifically question 12, which pertains to color vision.

And that may be possible because the 3 proteins in the fusion complex have different kinetics. Although they’re all in the millisecond range, there are subtle differences that neurons in the eye may be able to encode and patients may be able to differentiate. We need to probe that further, so it’s an iterative process. We’re seeing things we couldn't even imagine, with patients reporting improvements in color vision and visual acuity approaching what we thought were the theoretical limits of optogenetics.

Retinal Physician: As a scientist who spent more than a decade developing MCO-010, what does reaching the FDA review stage mean to you personally?

Dr. Mohanty: Working from the molecular level, from discovering and engineering the molecule all the way to this stage, has been very gratifying. We are especially thankful to the patients and their families, and I’ve had the opportunity to interact with them, even though I’m not a clinician but a PhD scientist. They have expressed their gratitude to us and how thankful they are that we’ve worked so hard on this technology. And we are now showing durable vision restoration for up to 4 years. This has been possible not just because of me, but because of our entire team working very hard and persistently to improve vision in these patients.

Retinal Physician: Could MCO-010’s potential extend beyond inherited retinal diseases to other conditions?

Dr. Mohanty: The only thing I would like to add is that this is not only a mutation-agnostic or gene-agnostic approach, which is very important for this inherited retinal disease (IRD) patient population, where 40% of patients do not know their pathogenic mutation. It has not yet been identified as being associated with their disease. More than that, we are proving now this can be a disease-agnostic approach, which is very, very important. This includes diseases that are not monogenic but involve polygenic or epigenetic mechanisms, such as geographic atrophy, where there is no treatment option to restore vision.

I'm very happy to report that Japanese regulators have recognized the mechanism of action and have allowed priority review of our product across all inherited retinal dystrophies—dozens of them. It's very difficult to develop and obtain approval for each of those patient groups. It would take us hundreds of years to get approval that way. But if this is approved, it will give hope to these patients, and we can collect more real-world evidence and bring this treatment to patients across the globe—not only giving them hope but also improving their quality of life. RP