ER-100 Epigenetic Therapy: First Human Dosed in Phase 1 Trial

A new ER-100 epigenetic therapy from Life Biosciences has reached its first human patient. The Boston-based biotech has dosed a Phase 1 first-in-human study of a gene therapy designed to rewind cellular age.

The treatment, the ER-100 epigenetic therapy (AAV2-OSK), targets optic neuropathies. These are eye conditions caused by damage to the optic nerve. Animal testing was first run on rodents and primates. The company then said the first human had received the candidate.

"This is the first-ever epigenetic restoration candidate approved for clinical trials, and if successful, treatment with ER-100 would be the first time cells have been rejuvenated in humans," Life Biosciences said in a press release.

How the OSK gene therapy works

The ER-100 epigenetic therapy delivers three proteins — Oct4, Sox2, Klf4 — together known as the OSK factors. The trio drives partial epigenetic reprogramming. The goal is to reset cellular age and restore function in old or damaged cells.

This OSK approach has a Nobel pedigree. Sir John B. Gurdon and Shinya Yamanaka shared the 2012 Nobel Prize in Physiology or Medicine. They showed that ordinary cells can be reverted to stem cells using such factors.

How epigenetic drift drives ageing

A person's DNA sequence stays largely fixed across life. But the epigenetic code, which sets which genes turn on or off, shifts with time.

Smoking, alcohol use, ageing, disease, and injury can all push these changes. The buildup can drive cancer. It can also drive neurological disease.

ER-100 sends direct genetic instructions into cells. The three OSK proteins then act as an "on" switch. They reset the harmful changes that build up over the years.

Which conditions ER-100 targets

The Phase 1 first-in-human study will enroll patients with two sight-threatening eye diseases. Both conditions damage the optic nerve:

• Open-angle glaucoma (OAG): a chronic, progressive disease where the eye's drainage system clogs. Pressure builds. Side vision goes first, then loss spreads slowly.
• Non-arteritic anterior ischemic optic neuropathy (NAION): often described as a mini-stroke of the optic nerve. Reduced blood flow to the back of the eye causes sudden sight loss, usually noticed on waking, and usually in one eye.

Both leave patients losing sight.

Sinclair on epigenetic age reversal

"This is an important moment for Life Bio and for the field of ageing biology," David Sinclair said. Sinclair is the co-founder of Life Biosciences and a professor of genetics at Harvard Medical School. He framed the milestone for the ER-100 epigenetic therapy program.

Sinclair added that the team's view of ageing turns on epigenetic information loss, not damage that cannot be undone. He explained: "Our research has suggested that ageing 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."

What Life Biosciences plans next

Beyond ER-100, Life Biosciences said it is building applications across multiple organs. A second candidate aimed at liver disease is already in testing. The team is also pushing the cell-resetting approach toward additional organ systems.

The ER-100 epigenetic therapy program reflects a wider belief that age-related disease can be slowed, halted, or reversed at the cellular level.

Competitors in the age-reversal field

Life Biosciences is not alone in probing Yamanaka factors to extend life expectancy, reverse ageing, or address disease. No therapeutic uses have yet been cleared in this space. But investor interest keeps climbing.

Retro Biosciences, a US firm backed by OpenAI's Sam Altman, says it wants to add ten healthy years to the human lifespan by treating age-related diseases.

Shift Bioscience, a UK biotech based in Cambridge, uses the same OSK mechanism to attack the underlying cause of age-driven disease.

For ophthalmology and ageing-research teams, the milestone marks a key step for partial epigenetic reprogramming in patients. Coverage on Medigear.uk tracks how the ER-100 epigenetic therapy reshapes the field.

Source: Originating coverage based on Euronews reporting on Life Biosciences' first-in-human Phase 1 study of ER-100 (AAV2-OSK), an epigenetic gene therapy for open-angle glaucoma and non-arteritic anterior ischemic optic neuropathy, with comments from David Sinclair, co-founder of Life Biosciences and professor of genetics at Harvard Medical School. Funded by Life Biosciences.