There have been stem cell trials for retinal repair going on in various locations around the world since the FDA approved their use for retinal repair research in 2010.
Warning: there are no FDA-approved stem cell trials outside of research. Why is that important? Check out the first article in this series for the details.
The Problems in Early Research
The goals of the continued clinical trials are to solve these problems:
- There have been ethical issues with using embryonic stem cells related to religious and political disputes about when life begins.
- Early research using embryonic stem cells found that these cells were often rejected. That means that if they are used, the participant takes immunosuppressant drugs exposing them to other diseases. Also, early research found that sometimes these cells migrated and caused tumor growth outside the eye.
- Stem-cell-induced RPEs injected in a suspension under the retina didn’t stay in that area to integrate with the person’s RPE cells.
- The method of getting these stem-cell-induced RPEs into the retina through a surgery called a vitrectomy adds to the risk of adverse effects such as retinal detachments.
I am greatly simplifying this topic because it IS complicated! If you would like a detailed review of this period of time, check out Retinal stem cell transplantation: Balancing safety and potential. It’s written using highly-technical language, but I think the conclusion is clear:
“The promise of stem cell therapy to preserve or restore vision in retinal degenerative diseases is finally taking shape. Whereas a decade ago, such ideas were confined to basic and translational laboratories, in the current era, stem cell transplantation into the retina is finally in human clinical trials in the setting of well-run registered clinical trials with the oversight of the FDA and appropriate ethical and safety review infrastructure built in. These aspects promote the protection of study subjects from undue harm, and facilitate the dissemination of the results to the scientific community and the peer review process.”
Status as of 2018
If I counted correctly, there are 18 clinical trials listed in a chart in the article Stem Cell Therapy in Retinal Disease. Sometimes they are called ‘RPE transplantation.’ They vary in:
- location of the research: US, UK, Japan, China, and others.
- source of the stem cells: embryonic, autologous cells which are cells taken from the participant (bone marrow, blood, skin).
- how the stem-cell-induced RPEs are organized:
- loose in a suspension which is a fluid or
- on a single layer of some kind of material (monolayer) that connects them to keep them together. This simulates how normal RPEs are positioned on Bruch’s membrane. The designs and composition vary, but some other terms for this approach are patch, scaffold, layer, implant, or sheet.
- type of delivery method: injected into the vitreous fluid or inserted below the retina using various procedures.
- type of retinal disease: AMD both wet and dry, Stargardt’s Disease, Myopic Macular Degeneration and Glaucoma.
Status in 2020
There are 3 stem cell clinical trials that have been making headlines in late May and early June 2020.
London Project to Cure Blindness
In 2015 in a phase 1 UK clinical trial, stem-cell-derived RPEs on a patch were inserted into the retinas of 2 people who had vision loss from wet AMD. In 2018, it was reported that they had gone from not being able to read at all, even with glasses, to reading 50-80 words per minute with normal reading glasses.
A recent update said that 5 years later, these 2 people have retained this improvement. There are other people enrolled in this clinical trial. When the COVID-19 lockdown has lifted, they will be treated.
Lineage Cell Therapeutics OpRegen Clinical Trial
For those who have advanced dry AMD called geographic atrophy (GA), there are 2 issues:
- There are areas of no vision from dead photoreceptors which are called scotomas or blind spots.
- These scotomas continue to grow and vision loss gets worse.
In 2015, the company Lineage Cell Therapeutics started a phase 1/2a clinical trial in locations in the US and Israel using their biologic product OpRegen. OpRegen is a suspension containing human embryonic stem cells. There were 4 cohorts (groups) where the treatment varied by the severity of the GA of the participant, 1 of 2 forms of the suspension, the delivery system used, and the number of cells use. For some of the participants they used a delivery system they developed called Orbit Subretinal Delivery System which delivers the stem cells into the retina without the need for a vitrectomy.
The FDA ‘fast tracked’ the clinical trial because “the drug fills an unmet medical need in a serious condition.” That means it will get faster communication and review with the FDA (more details in ‘BioTime’s Subsidiary Cell Cure Neurosciences Ltd. Receives FDA Fast-Track Designation For OpRegen® For The Treatment Of The Dry Form Of Age-Related Macular Degeneration.’
Preliminary data for the 5 participants in cohort was presented in 2020. The findings were:
- The stem cell product and new delivery system were safe and well tolerated in all 17 participants.
- For 5 people, there was an average of a 10 line increased in visual acuity over the 15-month followup period.
- Testing showed improvement of the RPE area with a reduction of the amount of drusen and a decrease in the size of the scotomas of some participants.
National Eye Institute
After positive results using animals, the National Eye Institute announced a Phase 1/2a clinical trial in which a person’s own blood will be used to create stem-cell-induced RPEs that will be transplanted into the retinas of 12 participants who have geographic atrophy. There are two important aspects of this clinical trial:
- By using a person’s own cells, it reduces the chance that the body will reject them. That reduces the need for Immunosuppressant drugs.
- The stem-cell-derived RPEs are put onto a single-cell (monolayer) biodegradable scaffold or patch. It’s the first clinical trial in the US to do this.
As a phase 1/2 trial, the participants will be monitored for a year for adverse events to make sure that the stem cell patch and procedure to insert it are safe. Based on the promising results of past stem cell clinical trials, they also hope to see improvements in visual acuity.
Hope for Those With Vision Loss
Vision loss from the advanced stages of any type of macular degeneration is devastating. This line of research has advanced greatly in 10 years. There have been promising results so far. Current and future research is building on those results to give HOPE that vision loss can be stopped and even reversed!!
