ER-100 Clinical Trial for Glaucoma: What We Know So Far and What to Expect

ER-100: A New Gene Therapy Trial for Glaucoma and Optic Neuropathies

Glaucoma is a leading cause of permanent vision loss worldwide. It happens when the delicate nerves that carry images from the eye to the brain (the retinal ganglion cells, or RGCs) are damaged or die. In most glaucoma patients, this nerve damage is linked to high intraocular pressure (eye pressure), so current treatments (eye drops, lasers, or surgery) focus on lowering that pressure (pmc.ncbi.nlm.nih.gov) (www.lifebiosciences.com). However, even with good pressure control, many patients continue to lose vision over time. In fact, some people develop “normal-tension” glaucoma, where their eye pressure is never high, yet the optic nerve still deteriorates (www.lifebiosciences.com) (pmc.ncbi.nlm.nih.gov). This shows that glaucoma therapies based only on pressure relief can slow the disease but cannot reverse it.

Another related condition, non-arteritic anterior ischemic optic neuropathy (NAION), causes sudden vision loss due to poor blood flow to the optic nerve (often called “stroke of the eye”). Unfortunately, there are no approved treatments for NAION, so patients have to wait and hope for some natural recovery, which often never comes (www.lifebiosciences.com).

Because of these gaps – few ways to actually protect or restore the optic nerve – researchers are excited about a completely new approach called ER-100. This is an experimental gene therapy being tested in a Phase 1 clinical trial (starting in 2026) for people with open-angle glaucoma or recent NAION. ER-100 does not target eye pressure at all. Instead, it aims to rejuvenate the aged or damaged cells in the retina and optic nerve by turning back their “cellular clock” (www.lifebiosciences.com) (longevity.technology). In simple terms, ER-100 delivers genetic instructions to the eye’s nerves that may help them behave like younger, healthier cells.

How ER-100 Works: “Partial Reprogramming” of Eye Cells

ER-100 is a first-of-its-kind therapy based on partial epigenetic reprogramming. It makes use of a discovery by Nobel laureate Dr. Shinya Yamanaka (who found that certain genes can reset a cell’s age). Specifically, ER-100 carries three of the four Yamanaka genes – OCT4, SOX2, and KLF4 (often abbreviated OSK) – into the eye (www.lifebiosciences.com). These genes are delivered by harmless viruses (modified adeno-associated viruses, or AAVs) injected directly into the gel of the eye (the vitreous) (ichgcp.net). Once in the retinal nerve cells, the viral carrier gives those cells the instructions to make the OSK proteins. The idea is that the OSK proteins will reset some of the cells’ molecular markers – their epigenetic marks – restoring a more youthful gene activity pattern without actually changing the cells’ DNA (www.lifebiosciences.com) (ichgcp.net).

Importantly, ER-100 uses a safety feature: the OSK genes are under control of a “switch” that responds to doxycycline, a common antibiotic (ichgcp.net) (longevity.technology). Patients in the trial will take low-dose doxycycline for about 8 weeks after the injection. This enables the OSK genes to turn on only during treatment. Once the doxycycline is stopped, the cells reduce OSK activity. This makes it transient gene therapy (temporary gene expression) aimed just at re-setting cell age rather than permanently changing the cells.

Because ER-100 only delivers three factors (leaving out the fourth Yamanaka factor, c-Myc, which is linked to tumor risk), the company hopes to avoid causing cells to become stem-like or cancerous (longevity.technology). In lab animals, long-term continuous OSK expression did not cause uncontrolled growth or major side effects (pmc.ncbi.nlm.nih.gov) (longevity.technology). (Preclinical tests in mice and non-human primates showed ER-100 was well tolerated, with no significant toxicities (pmc.ncbi.nlm.nih.gov) (longevity.technology).) Overall, ER-100 represents a brand-new strategy: instead of a drug or surgery to improve drainage, it is a neuro-regenerative gene therapy that attempts to rescue and rejuvenate the optic nerve itself.

What Preclinical Studies Show

Before testing ER-100 in people, researchers needed evidence that it could be both effective and safe in animals. Several studies in glaucoma and optic nerve injury models have been very encouraging:

• In mice with glaucoma-like eye damage, two months of OSK gene therapy fully restored vision (pmc.ncbi.nlm.nih.gov). The treated mice recovered eyesight to near-normal levels, and the improvement lasted for many months. Notably, even after 21 months of continuous OSK treatment, the mice showed no adverse effects on their retinal structure or weight (pmc.ncbi.nlm.nih.gov). This suggests the rejuvenation process can work without harming the eye.

• In other animal studies, scientists have repeatedly seen nerve cell recovery. For example, Dr. David Sinclair (co-founder of Life Biosciences) and colleagues previously reported that OSK factors restored vision in blind mice after optic nerve injury (longevity.technology). These experiments showed that injured nerve cells could be “brought back to life” by resetting their epigenetic marks.

• In non-human primates (monkeys), Life Biosciences tested ER-100 for safety. According to company researchers, ER-100 was well tolerated in primates with no significant toxicities or organ damage (longevity.technology). These primate studies – although not published in a journal – support the idea that local injection of OSK genes into the eye does not cause dangerous side effects in larger eyes.

Taken together, the lab findings allowed the company to ask the FDA to run a human trial. As summarized by Life Biosciences, their animal work demonstrated “controlled OSK expression, restoration of methylation patterns, and improved visual function” (www.lifebiosciences.com) – key proof-of-concept that paved the way for testing ER-100 in patients.

The ER-100 Clinical Trial: Design and Goals

Life Biosciences sponsored this trial. It is a Phase 1, open-label study primarily designed to show safety and tolerability in humans (longevity.technology) (www.lifebiosciences.com). The trial number on ClinicalTrials.gov is NCT07290244, and it began enrolling in early 2026 (www.lifebiosciences.com). Up to 18 patients will be treated: 12 with open-angle glaucoma (OAG) and 6 with recent NAION (ichgcp.net).

Key features of the trial include:

• Single Dose Injection: Each participant receives one injection of ER-100 in one eye (the affected eye). After the injection, they take an oral course of doxycycline for 8 weeks to activate the gene therapy (ichgcp.net).
• Follow-Up Visits: Patients will have an intensive follow-up schedule. It includes about 9 clinic visits in the first 6 months and then yearly check-ins up to 5 years total (ichgcp.net) (www.clinicaltrialsarena.com). This long follow-up is to watch for any delayed side effects and to see lasting benefits.
• Visual and Health Assessments: At each visit, participants get full eye exams and visual tests. These may include measuring visual acuity (reading an eye chart), visual field testing (peripheral vision test), and imaging of the retina and optic nerve. Doctors will compare these results to each patient’s baseline (before treatment) to see if vision stays stable or improves (www.lifebiosciences.com) (longevity.technology).
• Safety Monitoring: The trial will track side effects through exams and lab tests. For example, doctors will monitor for inflammation or other eye problems, and blood tests may check for immune reactions to the viral therapy (www.clinicaltrialsarena.com) (longevity.technology).
• Biological Sampling: Participants will provide samples of tears, saliva, urine, and stool. These samples help researchers understand how the therapy moves through and leaves the body (www.clinicaltrialsarena.com).
• Quality-of-Life Questionnaires: Patients also fill out questionnaires about vision-related quality of life. This helps gauge any change in daily function or well-being (www.clinicaltrialsarena.com).
• Immune Response Measures: Because gene therapy can trigger an immune reaction, the trial specifically measures immune responses. The doctors will check whether the body raises antibodies against the therapy (www.clinicaltrialsarena.com).

The trial has two parts (cohorts). First, a dose-escalation phase in the glaucoma group: three glaucoma patients will get a low dose, followed by three at a higher dose. A safety board will watch each step before moving to the next dose. After completing glaucoma dosing, the team will choose a dose and give it to the NAION patients (initially 3, and then up to 6 total) (ichgcp.net). This means the glaucoma group helps find a safe dose before treating NAION patients.

Who can join? Eligible participants are adults (ages 40–85) with either:

• Open-Angle Glaucoma (OAG) in one eye, with moderate vision loss but eye pressure under 30 mmHg (ichgcp.net). They should be on stable glaucoma therapy (drops, etc.) and not need any glaucoma surgery soon.
• NAION in one eye, with sudden vision loss within about 2 weeks before screening, confirmed by an eye specialist (ichgcp.net). The NAION-affected eye needs to still show some viable vision and signs of optic nerve swelling on exam. Patients must have clear eye media (able to be dilated), good general health, and agree to the follow-up schedule (ichgcp.net) (ichgcp.net). Pregnant women are excluded, and men and women of childbearing potential must use birth control during the study. (ichgcp.net)

Currently, the trial is listed as not yet recruiting, but it is expected to start soon. The first patients are planned to be enrolled in 2026, and the company anticipates the earliest results might emerge by late 2026 or early 2027 (trial.medpath.com). (Keep in mind this is just an estimate – clinical trials often take longer than expected.)

For now, the only listed study site is at Global Research Management in Glendale, California (ichgcp.net). Future sites (for broader recruitment) may be added if the trial expands. Patients or doctors interested can follow the trial registration (NCT07290244) for updates or contact Life Biosciences for more information.

How ER-100 Differs from Existing Glaucoma Treatments

All approved glaucoma drugs and surgeries work on one problem: intraocular pressure (IOP). Eye drops either reduce fluid production or improve outflow, which can slow nerve damage. However, none of these treatments directly heal or regrow damaged optic nerve cells. That is why many patients keep losing vision over time and why a normal pressure patient can still go blind (pmc.ncbi.nlm.nih.gov) (www.lifebiosciences.com).

By contrast, ER-100’s goal is to repair the nerve cells themselves. It is the first glaucoma therapy (and perhaps the first for NAION) ever tested in humans that uses epigenetic reprogramming to try to restore retinal neurons (www.lifebiosciences.com). In other words, instead of addressing just the symptoms (pressure), it tackles a root cause – the aged state of the cells. If successful, this could open the door to regenerative treatments that complement pressure-lowering drugs.

In clinical terms, ER-100 is intended as a disease-modifying therapy. Life Biosciences explicitly notes current care “fail[s] to address the underlying neuronal degeneration,” leaving “a significant unmet medical need” for therapies that protect or regenerate vision (www.lifebiosciences.com). ER-100 aims to fill that gap by using the OSK factors to encourage the damaged RGCs to recover function. Because it acts on epigenetic mechanisms (the protein markers and gene activity inside cells), it represents a novel mechanism not seen in any available glaucoma treatment.

It’s too early to know if ER-100 will actually lower IOP. In fact, the trial does not target pressure at all – it treats the optic nerve directly. Any effect on eye pressure is a secondary concern. If ER-100 works mainly by neuroprotection/regeneration, it would be a major shift for glaucoma care. Even if it does not improve vision on its own, it could potentially be used alongside drops or other therapies to give patients a better chance of preserving sight.

In summary, the unmet need ER-100 addresses is clear: the lack of any treatment that can regenerate optic nerve cells or restore lost vision in glaucoma/NAION. All existing therapies only slow damage. ER-100 is unique in trying to reverse damage at the cellular level.

What Patients and Caregivers Should Know

• This is an experimental trial. ER-100 is not approved for general use. It is currently in a very early Phase 1 study to test safety. Patients should understand this is a research experiment, not a proven cure. Benefits are uncertain, and there are unknown risks.

• Who might join? Adult patients who meet the criteria (moderate glaucoma or acute NAION) and can get to the study center may consider screening. Talk with your eye doctor about trial eligibility. To get enrolled, you would need to consent to the study and follow its schedule. (Life Biosciences has an email contact and a ClinicalTrials.gov listing for NCT07290244 with more details.)

• What happens in the trial? Each participant will get one injection of ER-100 in one eye, followed by oral drops of doxycycline for about two months. Then doctors will monitor you closely: frequent eye exams, imaging (like OCT scans), vision tests (eye charts and visual fields), and lab tests over the next months and years (ichgcp.net) (www.clinicaltrialsarena.com). You will also fill out questionnaires about your vision and quality of life. These assessments are mostly like routine clinic visits but include some extra checks (like collecting tears or blood at times).

• Follow-up and safety: Trial staff will watch you for side effects. Since ER-100 is a gene therapy, they pay special attention to inflammation or immune reactions. The follow-up is lengthy (almost 5 years) to catch any late issues. Your doctors will compare every visit’s results to your baseline from before treatment to see any changes.

• Possible benefits and risks: We do not know if ER-100 can improve vision in human patients – that is a question for future trials. In this Phase 1, the first goal is confirming that an injected dose of ER-100 is safe. If the therapy has any positive impact on vision measures during the trial, that would be encouraging (but any such findings will need larger studies to confirm) (longevity.technology). Potential risks include inflammation, increased eye pressure, or unexpected effects of gene therapy. The trial design includes many safeguards (low dose, antibiotic switch, local delivery to the eye) to minimize risk (longevity.technology), but unknown problems could still occur.

• After the trial: If ER-100 shows a safe profile and hints of benefit, Life Biosciences may plan Phase 2 trials in more patients. Eventually, if all goes well over several years, ER-100 might seek regulatory approval. However, this is a long process – even if this study goes smoothly, it could be several years before ER-100 (or any similar therapy) becomes commercially available.

Conclusion

ER-100 represents a bold, novel approach to treating glaucoma and NAION. By trying to reset the age of retinal nerve cells, it could offer hope for a treatment that goes beyond pressure control. The upcoming trial will tell us whether this gene therapy can be given safely to patients. For now, patients should stay informed: if you or a loved one fit the criteria, you and your doctor might consider this opportunity. Regardless of the outcome, ER-100 is already contributing valuable knowledge about the possibilities and challenges of repairing the aging eye.

Clinicians and researchers will watch closely. A safe and promising result could spark a wave of new studies in ocular gene therapy and neuroprotection. If ER-100 ultimately proves effective, it could change the landscape of glaucoma treatment, addressing an urgent unmet need. Until then, the main takeaway for patients is cautious optimism: this trial is a first step toward a potential new way to fight glaucoma, but it will require rigorous science and time to know if it truly lives up to its promise.

Sources: The information above is drawn from Life Biosciences press materials and news reports, as well as peer-reviewed studies on OSK gene therapy (www.lifebiosciences.com) (ichgcp.net) (pmc.ncbi.nlm.nih.gov) (longevity.technology).