Gene therapy that regrew mice's optic nerves begins human testing

Yuancheng "Ryan" Lu, a geneticist at the Whitehead Institute in Cambridge, Massachusetts, has developed a gene therapy that uses an age-reversal technique called reprogramming to repair damaged optic nerves. Lu created the approach as a Harvard Medical School PhD student, and a version of it entered human trials this year.

In 2018, Lu crushed the optic nerves of mice, blinding them, then injected their eye cells with a gene therapy designed to restore a youthful state. Sixteen days later, the nerves were growing back, with axons visible under a microscope as thin orange filaments. Later tests in a box with rotating bars of light showed the mice tracking the movement, meaning they could see again. The result was published in the journal Nature in 2020.

Reprogramming is the process that resets DNA inside an embryo, which is why babies are born young, not old. In 2006, Japanese researchers showed it could be triggered in the lab by adding four specific genes to a cell, turning it into a stem cell that behaves as if plucked from an embryo. One of the four, called Myc, is most likely to cause dangerous changes such as cancer, so Lu built his therapy from just the other three genes, leaving Myc out. His insight was to test this trimmed therapy on the optic nerve, since the eye is particularly accessible.

On June 9, the startup Life Biosciences announced it had injected a version of the therapy, now called ER-100, into the eye of a person with glaucoma, its first use in a human patient.

Lu says the therapy remains toxic to many types of cells, and different factors drive aging in each one. This year, he identified a gene that protects the retina from damage caused by free radicals, the main cause of age-related macular degeneration. He describes his original mouse work as a proof of concept rather than a finished cure.