Life Biosciences, a Boston startup cofounded by Harvard professor David Sinclair, has received FDA approval to begin testing a rejuvenation treatment called ER-100 in human volunteers. The company will initially target glaucoma, a disease in which high pressure inside the eye damages the optic nerve, but executives and some investors see the study as an early test of whether age-related decline in human tissues can be reversed. The trial follows years of preclinical work on cellular “reprogramming,” a concept that has drawn hundreds of millions in funding from Silicon Valley outfits such as Altos Labs, New Limit, and Retro Biosciences.
The experimental therapy builds on Nobel Prize winning research showing that introducing a small set of genes, known as Yamanaka factors, can reset adult cells into stem cells similar to those in an early embryo. Because fully turning cells back into stem cells can cause tumors, scientists developed the idea of “partial” or “transient” reprogramming, in which exposure to a subset of these factors is limited to avoid erasing the cell’s identity. In Sinclair’s 2020 study in mice, partial reprogramming using three genes, referred to as OSK, was reported to restore vision after optic nerves were crushed, work that inspired Life Biosciences to focus its human trial on the eye.
In the new study, viruses carrying three reprogramming genes will be injected into one eye of about a dozen patients with glaucoma, according to a description of the study first posted in December. To help control the process, the reprogramming genes will be under a special genetic switch that activates them only when patients take a low dose of the antibiotic doxycycline, and initially patients will take the antibiotic for about two months while the effects are monitored. The switch is built from gene components taken from E. coli and the herpes virus, and scientists say it could potentially provoke an immune response because this antibiotic based control system has not been used in humans before. Researchers also caution that the OSK factors are expected to turn on hundreds of other genes and, in some settings, can push cells into a primitive stem cell like state that may increase cancer risk.
Supporters such as investor Karl Pfleger describe reprogramming as “like the Artificial Intelligence of the bio world” and view Life Biosciences as the furthest along toward human testing, even as other companies like New Limit and Shift Bioscience focus on identifying safer or more precise gene combinations and remain years away from clinical trials. Critics of Sinclair note his history of promoting sirtuins and resveratrol as longevity fixes and argue he has overstated progress, concerns summarized in a 2024 Wall Street Journal profile labeling him a “reverse aging guru” whose ventures “have not panned out.” Life Biosciences itself has restructured since its 2017 founding, abandoning a multi subsidiary strategy after limited progress and hiring CEO Jerry McLaughlin in 2021 to center the business on Sinclair’s mouse vision work.
Within the aging research community, there is disagreement about whether reprogramming truly constitutes age reversal, and even proponents acknowledge the first ER-100 trial should be seen as a proof of concept rather than a step toward near term whole body rejuvenation. Life Biosciences has discussed ambitions to extend reprogramming to organs such as the brain, and Sinclair has advanced a theory that gradual loss of correct epigenetic information is the root cause of aging, a notion he says aligns with Elon Musk’s public speculation that aging has a “very solvable” and “obvious” explanation. For now, though, industry figures like Pfleger stress more modest goals, saying that the best case is that the therapy “solves some blindness for certain people and catalyzes work in other indications,” and even competitors such as Shift’s CEO Daniel Ives acknowledge that Life Biosciences is “way ahead of anybody else in terms of getting into humans” by starting in the eye, which he calls a “nice self contained system” where, if the treatment fails, “you’ve still got one left.”
