New Developments in Optic Nerve Regeneration – Interview with Petr Baranov
In June 2024, we interviewed Dr. Petr Baranov, a researcher at the Schepens Eye Research Institute at Mass Eye and Ear, who is working on developing cell replacement therapy for glaucoma and optic neuropathies.
In ADOA, optic nerve damage is the primary cause of vision loss. In some individuals, ADOA progression is severe, resulting in significant loss of optic nerve cells. This results in only 5-10% remaining vision. In these individuals, treatments aimed at slowing or stopping the disease would have little benefit. However, regenerating or replacing the optic nerve cells could potentially restore vision. We have been following these developments for some time, see also episode 11 of the Road to Treatment.
ADOA involves damage to the retinal ganglion cells (RGCs), the cells responsible for transmitting visual information to the brain. Dr. Baranov discussed his lab’s goal of replacing these cells and reconnecting them to the brain. He explained that in the past there was a lot of excitement about injecting stem cells into a person’s eye to restore vision, but the idea of simply putting stem cells into an eye did not work and in many cases caused permanent damage. Therefore, clinics that offer stem cell therapies to restore vision can be very dangerous. Instead, Dr. Baranov’s lab is working on cell replacement therapy, which works differently.
RGC replacement therapy involves taking a blood sample, converting the blood cells into pluripotent stem cells, and then converting them into retinal organoids (3D structures that will grow into RGCs). These lab-grown retinal organoids can then be transplanted into the eye. This has been done experimentally in mice, but simply transplanting a retinal organoid into a mouse is not enough for the mouse to see. The biggest challenge is figuring out how to connect these new cells to both the eye and the brain. The work of Dr. Baranov’s lab involves creating the right microenvironment for these new cells to grow. He compares this to the way a seed cannot grow without the right soil; a cell also needs the right conditions to grow and form connections.
Dr. Baranov emphasized that cells do not have to come from the affected person and that blood from a healthy donor can be used instead. This approach makes it possible to create and use standardized cells that can be used for any individual. In essence, cells from a single healthy person can be implanted into thousands of patients (including those with ADOA, as well as those with glaucoma or other optic neuropathies). For pharmaceutical companies, using standardized cells has great advantages, as this approach leads to easier quality control and faster approval processes. Using donor cells would likely require only minimal or localized immunosuppression (suppression of the immune system so that the body does not reject the implanted cell). This is because the eye is considered “immune-privileged,” meaning that the body’s normal immune response is limited within the eye.
As for the lab’s next steps, the hope is to move from animal studies to humans. While animal studies can often show whether a therapy will be safe, they cannot always predict whether that treatment will be effective. Due to the technology and processes involved, research can only proceed with adequate funding, and Dr. Baranov is actively working to raise money to continue their research. While a timeline is difficult to predict, the hope is that human trials can begin within the next 4-5 years. Dr. Baranov also mentioned that his lab is not the only one working on this approach, and that he is collaborating with many other researchers and organizations working on various aspects of the project.
Regeneration is a radically new approach that does not aim to repair existing cells, but rather to replace them with new, healthy cells. In this sense, it is different from other approaches that only attempt to slow or stop the disease, such as neuroprotection, RNA and gene therapies (which are still beneficial for those with remaining vision). This is a very exciting development and we will continue to follow Dr. Baranov’s work in the years to come!
Summary of the meeting by Peter and Olivia
