Life Biosciences Starts First Human Partial Reprogramming Trial

Life Biosciences will start the first human trial of partial cellular reprogramming for eye disease later this year. The company plans to deliver three Yamanaka transcription factors – Oct4, Sox2 and Klf4 – by viral vector into one eye of up to 12 patients with glaucoma and six patients with nonarteritic anterior ischemic optic neuropathy (NAION). Participants will be monitored for five years for clinical and safety outcomes.

Life Biosciences, founded by Harvard scientist David Sinclair, plans to test whether the treatment can restore retinal nerve function damaged by age-related degeneration or sudden optic nerve loss. Only the affected eye will receive the injection so investigators can compare it with the untreated eye.

The Yamanaka factors can reprogram adult cells. The full set includes a fourth factor, c-Myc, which is associated with increased cancer risk. The company is using a three-factor regimen that omits c-Myc to lower oncogenic risk while aiming to preserve regenerative effects.

Preclinical studies underpin the trial. In mice, Yuancheng Ryan Lu, a former student of Sinclair, reported regeneration of eye cells and improved visual function after delivery of the three factors. Investigators reported similar studies in nonhuman primates that showed no signs of cancer or other severe adverse effects.

Vittorio Sebastiano, a biologist at the University of California, Irvine, warned that removing c-Myc reduces but may not eliminate cancer risk, noting that c-Myc drives rapid cell division and some partially reprogrammed cells might depend on that activity.

Life Biosciences’ chief scientific officer Sharon Rosenzweig-Lipson indicated participants will be followed for five years to track safety and efficacy. The trial is small and designed to test safety and proof of concept rather than to measure large-scale efficacy.

Regulators and independent scientists will monitor for any therapeutic signals and for evidence of uncontrolled cell growth or other adverse events. The study has drawn interest from investors and technology leaders who support anti-aging research.