We may be on the cusp of understanding whether we can turn back time for our cells to stave off age-related disease, with the first human receiving experimental gene therapy as part of a landmark trial.
The patient, who is part of a first-in-human phase I study with an estimated 18 participants, was injected with a single dose of ER-100 into the eye, marking the first time this anti-aging therapeutic moves beyond animal trials to assess the drug's safety and tolerability in humans.
This clinical trial could be the first step into an entirely new area of medicine, where we can "reprogram" aging cells to behave like young ones.
Delivered via injection to the eye, ER-100, from Life Biosciences (Life Bio), is made up of three cell-reprogramming genes tasked with rejuvenating damaged retinal neurons.
The trial is focused on the eye because it's a reasonably "contained" organ – if something goes wrong, adverse effects should remain localized. As such, ER-100 targets optic neuropathies such as open-angle glaucoma (OAG) and non-arteritic anterior ischemic optic neuropathy (NAION). Essentially, it's using gene therapy to tackle age-related optic degeneration.
Researchers are using a disabled virus, or an adeno-associated virus, as a vector to deliver the three rejuvenation genes into retinal nerve cells. The genes carry instructions for transcription factors OCT4, SOX2 and KLF4 (OSK), which produce proteins that have been shown to be able to turn mature cells into youthful versions of themselves – or induced pluripotent stem cells (iPSCs) – in earlier lab experiments.
OCT4, SOX2 and KLF4 are all Yamanaka factors, which are actually made up of four genes. However, the fourth one, c-MYC, has been strongly associated with cell proliferation that can lead to cancer growth, so it's been purposely omitted from the ER-100 therapy.
While this may sound straightforward, there's a reason anti-aging gene therapy has been slow to roll out in human trials. For this to have a chance of success, it needs to turn back the clock in existing cells – but not so far that they lose their identity.
Think of it like this: Every cell in the body holds the same DNA, but different cell types perform different jobs because they activate different sets of genes. A retinal ganglion cell, as targeted in this clinical trial, functions as part of the visual system because its gene activity maintains its identity as a retinal neuron.
If genes are activated for too long, mature cells can forget their role – or their identity. So, in the context of this trial, instead of creating a younger, healthier retinal cell, "uncontrolled reprogramming" could result in dysfunctional cells that no longer perform their normal role. And this raises the risk of these cells turning into cancerous growths.
“This is an important moment for Life Bio and for the field of aging biology,” says David Sinclair, co‑founder of Life Bio and Professor of Genetics at Harvard Medical School. “Our research has suggested that aging is driven in large part by the loss of epigenetic information, not irreversible damage. This clinical study represents the first opportunity to test whether restoring that information can ameliorate human disease.”
And while ER-100 may sound a little like human genetic engineering, there are distinct differences. It doesn't edit a person's DNA sequence – so it's not changing the genome – but instead introduces genes that deliver a code to reprogram how existing genes are used. And being able to turn mature cells into youthful ones has the potential to restore a suite of functions that are slowly lost with age.
In this retinal trial, scientists hope that the specific proteins encoded by the genes will trigger the regeneration of neurons in the optic nerve, which is damaged in glaucoma cases. Like neurons in the brain, these nerve cells can't regenerate once they've died off. While we're not there yet, being able to revive neurons could change how we treat age-related diseases like Alzheimer's.
“This milestone reflects years of rigorous scientific development and translational research,” says Sharon Rosenzweig‑Lipson, Chief Scientific Officer of Life Bio. “Our preclinical studies have demonstrated that controlled OSK expression can reset epigenetic patterns associated with healthy cellular function, improve tissue performance, and restore visual function in animal models.
"Advancing ER‑100 into the clinic is an important step toward translating epigenetic restoration into a new class of medicines for age-related diseases," she adds.
The phase I trial is expected to complete its initial stage around May 2027. Given the high-profile nature of this study, Life Bio is likely to release some findings earlier.
Regardless of the outcome, this is a milestone study that moves us a step closer to fighting age-related diseases in an entirely new way.
Source: Life Biosciences
Fact-checked by Mike McRae
