Global First: Cell 'Rejuvenation' Therapy Enters Human Trials

Scientists Attempt to Repair Optic Nerve Cells.

[Report] A highly anticipated gene therapy trial has recently been launched, with the first participant already treated. The therapy aims to induce senescent cells to revert to a youthful state.

This clinical trial is testing an innovative technology: partially reprogramming senescent cells by activating three genes to restore the physiological characteristics of young cells. Some scientists believe that partial reprogramming technology holds promise for rejuvenating organs. This trial will focus on whether activating these three genes can treat certain diseases, with glaucoma, a condition that can lead to blindness, as the primary target.

On June 9, Life Biosciences, the U.S. company leading the trial, announced that it had completed treatment for the first participant. The research team hopes that these gene-encoded proteins can promote the regeneration of neurons in the optic nerve. The optic nerve connects the eye to the brain; in patients with glaucoma, this nerve is damaged, and these neurons lack the capacity for regeneration.

The primary objective of the trial is to verify the safety of this reprogramming technology, a long-standing challenge in the field. Animal experiments conducted by multiple laboratories have confirmed that partial reprogramming can be performed safely; however, scientists remain concerned that the technology may induce carcinogenic transformation in certain cells.

“If it can be safely applied in humans, cellular reprogramming technology holds broad prospects. However, the technology is still in its early stages and carries a significant risk of causing serious side effects,” said Matt Kaeberlein, co-founder of the U.S. medical company Optispan. He noted that choosing the eye as the initial site for testing this technology is highly reasonable, as ocular interventions are unlikely to produce life-threatening side effects compared to other organs.

The core objective of partial reprogramming is to moderately reverse the aged state of somatic cells and restore youthful cellular characteristics, while avoiding excessive “reversion” that would cause the cells to lose their original differentiated morphology and physiological functions. In the laboratory, four genes can reprogram somatic cells into a stem cell-like state. Researchers at Life Biosciences selected three of these genes for their study.

In 2020, a research team led by David Sinclair at Harvard Medical School published a study in Nature stating that activating these three genes in mice with optic nerve damage could promote neuronal regeneration, thereby reversing vision loss in aged mice and those with glaucoma. Sharon Rosenzweig-Lipson, Chief Scientific Officer of Life Biosciences, stated that the company subsequently conducted experiments in rodents and monkeys, observing no serious side effects associated with the treatment.

The goal of this clinical trial is to treat 12 patients with glaucoma, after which patients with non-arteritic anterior ischemic optic neuropathy (NAION) will also be enrolled. NAION is an acute and severe condition that similarly causes optic nerve damage.

The research team employed a viral vector commonly used in gene therapy to deliver three reprogramming genes into retinal ganglion cells, whose axons constitute the optic nerve.

To further enhance safety, the system is designed with a tunable mode: the target gene is activated when the patient takes an antibiotic called doxycycline, and it is switched off after discontinuation of the drug. “This design enables precise control, allowing for the adjustment of gene expression to ensure it does not exceed the duration required for cellular rejuvenation,” said Rosenzweig-Lipson.

Pete Williams of the Australian Centre for Eye Research stated that even if this trial proves successful in effectively treating glaucoma and NAION, a core question remains to be answered: whether the modified cells have truly achieved “rejuvenation” and extended lifespan through this technology.

Rosenzweig-Lipson stated that the company’s current strategy is to tackle age-related diseases one by one. “We are not currently pursuing whole-body regeneration research; this is a long-term goal for the future, and it is still too early at present.” Life Biosciences has already tested cellular reprogramming technology in animal models of liver disease.

Williams is highly optimistic about this novel therapy targeting retinal nerve damage, but he expressed concern over the excessive attention the technology has received. “Expectations are currently too high. If a major adverse event occurs during clinical trials, progress in the field would suffer a severe setback.”

(Wang Fang)