Key Points:
- Partial reprogramming is a method for reverting cells back to an earlier stage of development, essentially making them younger.
- In nonhuman primates with laser-induced eye damage, partial reprogramming restored healthy neurons in the optic nerve — the nerve that transmits electrical signals from the retina to the brain.
- Reprogramming also restored electrical activity to the retina — the part of the eye necessary for vision.
On April 23rd, 2023, data was presented at the annual Association for Research in Vision and Ophthalmology (ARVO) conference in New Orleans showing that a new gene therapy utilizing partial (epigenetic) reprogramming restores visual function in nonhuman primates. Harvard professor, cofounder of Life Biosciences, and co-author of the study said:
“Demonstrating rejuvenation in nonhuman primates is a major step forward in advancing cellular rejuvenation as a way of treating both common and rare diseases in the eye and potentially other tissues. What we’ve learned in nonhuman primates has important ramifications for research on reversing aging and is likely to be highly translational to humans. This data moves us an important step closer to the first clinical trials of how cellular rejuvenation technology could treat aging-related diseases.”
He also posted this tweet:
Partial Reprogramming
In 2012, Japanese scientist Dr. Shinya Yamanaka won the Nobel Prize in Physiology or Medicine for “the discovery that mature cells can be reprogrammed to become pluripotent.” In other words, he essentially discovered how to turn an adult cell, like a skin cell, into a stem cell, which can become any cell in the body. He did this using what we now call “Yamanaka factors,” a set of four genes called Oct3/3, Sox2, Klf4, and c-Myc.
Stem cells are like young cells, ready to grow into any type of mature cell. Thus, reprogramming a cell can be thought of as making a cell younger. Indeed, in 2016, it was found that short-term (partial) activation of Yamanaka factors (partial reprogramming) could increase the lifespan of mice. Then, in 2020, Dr. Sinclair and his team, led by Yuancheng Lu (now a postdoc at MIT) found that just three of the Yamanaka factors (Oct3/3, Sox2, Klf4 – OSK) could restore vision in mice.
The Findings
The researchers used nonhuman primates to model a disease called non-arteritic anterior ischemic optic neuropathy (NAION). NAION is a condition whereby loss of blood flow to the optic nerve leads to vision loss. The optic nerve is an extension of the brain that connects to the retina in the back of the eye. The retina contains light-sensitive neurons that transmit electrical signals through the optic nerve to the brain, allowing us to see.
By shooting lasers into the eyes of the primates, the researchers induced NAION-like damage. This damage included altered electrical signaling, structural damage, and destruction of optic nerve axons — the part of neurons that rapidly transmit electrical signals. To treat this damage, the researchers used gene therapy technology to inject Yamanaka factors into the eyes of the primates one day after laser exposure. This led to improvements in electrical signaling and increased healthy optic nerve axons.
The electrical activation of light-sensitive neurons (rods and cones) and the transmission of electrical activity through the optic nerve to the brain is necessary for vision. Therefore, restoring this electrical activity and the axons that transmit this electrical activity should restore vision.
“NAION is the most common cause of acute optic neuropathy in people over 50, but currently has no effective treatment. The data we are presenting here show, for the very first time, that treatment with OSK can lead to significant recovery in affected visual function in an NHP model of NAION, the gold standard translational model. That potential unlocks new opportunities for cellular rejuvenation, not just in NAION but in other ophthalmic diseases that occur as a result of retinal ganglion cell dysfunction as we age,” said Dr. Bruce Ksander, Harvard professor and lead presenter of the study at the ARVO conference.
Life Biosciences
Life Biosciences is a biotechnology company that aims to reverse diseases of aging and injury. To achieve this, they are focused on partial reprogramming and autophagy research. Autophagy is the system our cells use to clear unwanted material. A decline in autophagy is a hallmark of aging; a key contributor to the aging process. OSK partial reprogramming was licensed by Life Bio from Harvard University and David Sinclair’s lab.
Addressing the latest nonhuman primate study findings, the CEO of Life Bio, Dr. Sharon Rosenzweig-Lipson said:
“We are delighted to present this truly groundbreaking data, which further validate Life Bio’s innovative approach to cellular rejuvenation. This approach has implications far beyond NAION and even the vision field, and we are pleased to share data that support the continued development of our scientific platform to address diseases of aging and restore human health.”
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