Newswise, June 27, 2017— There is great interest among glaucoma patients, scientists and doctors alike, in discovering regenerative therapies for the optic nerve and translating them from the laboratory to the clinic — and stem cell therapy is one of several promising approaches being studied.

Recently, we heard from a glaucoma patient who enrolled in a “patient-funded trial” in which the person paid $20,000 and received “stem cell injections” around one eye.

 Patient-funded trials are studies in which patients pay to participate. This approach was developed because clinical trials are expensive and funding from traditional sources (such as the NIH, pharmaceutical companies, or private foundations) is decreasing.

Although patient-funded research would appear superficially to provide an avenue for patients to obtain therapies under investigation, it is controversial for a number of reasons, both scientific and ethical.

Scientific considerations are deeply concerning: the gold standard for evaluating an experimental treatment is a randomized clinical trial in which participants are randomly allocated to the experimental treatment group or a control group that may not receive any treatment (placebo-controlled study), or may receive standard, approved therapies. Usually, study patients and doctors are both unaware of who receives which treatment and this study design minimizes bias towards a particular treatment.

In contrast, patient-funded trials do not have a control group, since it is extremely unlikely that patients would pay when there is a possibility of not receiving the experimental treatment.

 A control group is very important to determine if an experimental treatment really has an effect and also to compare the efficacy and risks of the experimental treatment versus other treatments. Although it is common in an early, “phase 1” trial to treat perhaps the first 3-12 patients in an open-label, non-randomized study, by “phase 2” trials, a randomized, masked design is ideal.

Even more concerning are the ethical considerations. These include disparity in access to the treatment, and risk of exploitation of vulnerable patients who have exhausted all treatment options and may be willing to undergo an unproven treatment at any cost.

In addition, a reported lack of proper oversight and monitoring for patient-funded trials implies the possibility that these may be thinly-veiled attempts to make money by the treating clinic or physician before proper FDA approval of new treatment methods.

Since a gold standard research study is not always feasible, decisions regarding the benefits and risks of a particular treatment may have to be made with the evidence at hand.

Given these considerations, we consulted Dr. Jeffrey Goldberg regarding stem cell therapy for glaucoma. Dr. Goldberg is a leading expert in therapies to regenerate the optic nerve and is part of the Catalyst for Cure team. His laboratory is developing novel stem cell approaches for glaucoma, and working steadily towards a translational program to bring discoveries out of the laboratory and into human testing once safety and efficacy in pre-clinical models is established.

Q: Dr. Goldberg, how might stem cells be helpful for patients with glaucoma?

A: Stem cells may be helpful for patients with glaucoma in different ways. Stem cells can be turned into trabecular meshwork cells in the front of the eye and transplanted in such a way as to lower eye pressure. This is an interesting approach but is not fundamentally about vision restoration.

A, For protecting or restoring vision, we really need to talk about stem cells in the back of the eye, at the retina. There, stem cells may have two positive effects. First, early in the disease, they may protect retinal ganglion cells from degenerating — providing a neuroprotective effect. Later in the disease when patients have lost considerable numbers of retinal ganglion cells and optic nerve axons, and have thereby lost considerable vision, stem cells may be useful to replace lost ganglion cells and restore the connections from the eye to the brain. This last approach—regrowing optic nerve fibers back to the brain—has been the most challenging but it’s also the most exciting.

Q. What is the current status of research on stem cell therapy for glaucoma?

A. Our laboratory and a number of other laboratories have made considerable progress on the two main fronts of bringing stem cell therapy to optic nerve restoration for glaucoma. First, we and others have discovered molecular pathways that can be used to coax stem cells to turn into neurons that look and act like real retinal ganglion cells. This will allow us to turn large numbers of stem cells into retinal ganglion cells for cell replacement therapy. Second, we are just beginning to make progress in transplanting retinal ganglion cells into the retina in pre-clinical models, to study their integration into the adult retina, how they respond to light and grow back down the optic nerve to the brain. Together these advances have brought us to an exciting moment in stem cell research for optic nerve restoration in glaucoma.

Q. Are you aware of any studies in which stem cell therapy stabilized or reversed vision loss from glaucoma?

A. Stem cells have not yet been properly tested in patients with glaucoma to look for their ability to stabilize or reverse vision loss. The careful move from the laboratory to clinical testing is still ahead of us, although with the intellectual energy and resources ready to deploy, such proper testing may not be far off.

Q. If your family member had vision loss from glaucoma, would you recommend stem cell therapy at this time?

A. I am often asked by my patients if they should sign up for a patient-funded trial for stem cells for glaucoma, and I am in the habit of counseling against this. I am not aware of any properly designed stem cell trials for glaucoma with well-tested cell therapies being moved to human testing at this time, but I do think these will come.

Q. Are there any risks or complications reported with stem cell therapy for glaucoma?

A. Indeed the risks for undergoing stem cell injections in any trial could be significant. Risks of infection, inflammation, and more severe vision loss will always be present; we are publishing a paper about 3 patients in the U.S. who participated in a patient-funded trial and lost significant vision due to severe inflammation in their eyes called endophthalmitis. These 3 unfortunate patients point to the importance of a cell therapy first undergoing proper testing in pre-clinical models before moving to human testing. Then, with properly designed and sequenced trials, I believe cell therapies can be safely tested in the eye as with the rest of the body. Indeed there are a number of cell therapies for macular degeneration already in human testing with a reassuring safety record thus far.

Q. What type of study would you design for evaluating stem cell therapy with glaucoma?

A. After demonstrating safety and efficacy of a cell therapy product in pre-clinical models, a small pilot study designed to assess for safety after injection in humans and analysis of the results should be the first step. After this, a move to a randomized trial with a control group and masked observers will be best to assess efficacy in phase 2 and eventually phase 3 trials.