First Patient Treated in Landmark Gene Therapy Trial for Glaucoma

A clinical trial testing a pioneering gene therapy approach to partially reprogram aged cells has treated its first participant.

The trial, sponsored by Life Biosciences, is evaluating the safety of activating three genes—OCT4, SOX2, and KLF4—to promote regeneration of optic nerve neurons in patients with glaucoma. The treatment is administered directly to the eye. The company announced the milestone on June 9.

Breaking Down the Science

This trial tests partial reprogramming, which involves turning on three of the four Yamanaka factors to rejuvenate cells without losing their specialized identity. The goal is to regenerate neurons in the optic nerve, which are typically unable to regenerate in adults and can be damaged in glaucoma, leading to vision loss.

Key Safety Considerations

Safety concerns include the risk of inducing cancerous states. However, animal studies in rodents and monkeys have not shown serious adverse effects, according to the company.

"The eye is a good first place to test the technique due to lower risks of life-threatening side effects." — Matt Kaeberlein, co-founder of Optispan

Researchers at Harvard Medical School reported in 2020 that activating these genes in mice promoted optic nerve regeneration and reversed vision loss in aged and glaucomatous mice.

Why the Eye?

The trial focuses on the eye because the risk of life-threatening side effects is considered lower than with other organs. This makes it a strategic starting point for human testing of this novel approach.

Expert Perspective

Matt Kaeberlein, co-founder of Optispan, noted that reprogramming has potential if it can be used safely, but acknowledged the technology is early and the potential for catastrophic side effects is high.

Background

Partial reprogramming has been studied in animal models as a method to reverse age-related decline. This trial is the first human test of the approach for treating a disease.