Potential of stem cell therapies offers hope for glaucoma treatment

December 6, 2019

Physicians have to be prepared to manage patients who may receive misinformation when it comes to the efficacy of stem cell therapies. 

Physicians have to be prepared to manage patients who may receive misinformation when it comes to the efficacy of stem cell therapies. 

This article was reviewed by Leslie Jones, MD

Ophthalmologists should advise their patients to perform their due diligence when participating in patient-funded clinical trials on stem cell therapies to treat glaucoma, according to Leslie Jones, MD, chairwoman of Ophthalmology at Howard University in Washington, D.C.

 “We need to be aware of what our patients are seeing in the media, that they are being marketed to,” said Dr. Jones, at the annual Sally Letson Symposium. “We have to caution them against things (trials) that are not controlled. They should approach with caution any marketing to participate in patient-funded stem cell trials.”

Related: Can glaucoma patients benefit from cell therapy approach? 

Dr. Jones noted that patient-funded trials have numerous weaknesses such as the lack of randomization and control arms, a disparity in access to the trials owing to their high fees, and an apparent risk of exploitation of vulnerable patients who are “reaching out for anything to improve their situation.”

Patients need to be informed that a trial appearing on a registry does not guarantee its scientific validity with respect to efficacy and safety, Dr. Jones explained.

According to Dr. Jones, clinicaltrials.gov is a registry that does not ensure that they are doing randomly selected trials or that there is informed consent or a proven effect of the therapy.

Unproven stem cell therapy treatments, often described as “cell therapy,” are readily available in the United States, with 351 businesses and more than 600 clinics, said Dr. Jones, noting the FDA has issued warnings about these treatments and the Federal Trade Commission has taken action as well.

Related: Cell therapy shows promise in glaucoma 
 

The availability of these treatments is not limited to the United States, with these therapies being offered north of the border as well to Canadians, said Dr. Jones. 

Indeed, 30 Canadian businesses are selling stem cell interventions provided at 43 clinics. Regen Med. 2018 Sep;13(6):643-658. 

Patients on both sides of the U.S.-Canada border need to look for red flags before they opt for current stem cell treatments. This can include whether they are being asked to provide informed consent, whether they have been told about the possible harms associated with the treatment, and if they are paying out-of-pocket for the treatment. 

Another red flag is the absence of other stakeholders in a trial, such as government agencies or research organizations. 

Related: Stem cell treatment: What could possibly go wrong with procedure? 
Adverse impacts

The adverse events that have developed after visits to “stem-cell clinics” have been documented and include severe bilateral vision loss subsequent to intravitreal injections of autologous adipose tissue-derived stem cells. N Engl J Med. 2017 Mar 16;376(11):1047-1053.

“They had their own adipose cells removed, and then spun down with various enzymes, and then injected into the vitreous cavity of the eye,” said Dr. Jones, describing in detail the treatment administered to these patients. 

“Some of the enzymes were so toxic that they caused lysis of zonules,” she added.

Another instance involved a woman who had exudative macular degeneration and underwent bilateral intravitreal injections and later developed retinal detachments in both eyes. Ophthalmic Surg Lasers Imaging Retina. 2017 Sep 1;48(9):772-775.

“The impact of these unproven therapies was very real,” said Dr. Jones, noting patients are paying a minimum of $5,000 per injection per eye.

Related: The Magnificent 7: How many glaucoma medications is too many?Stem cell therapies, glaucoma
The attraction of stem cells, or induced pluripotent cells created by various growth factors and transcription factors, is that they can revert back to the pluripotent state where they can develop into any kind of cell, Dr. Jones pointed out.

Several possible avenues of research are taking hold, such as differentiation of stem cells into trabecular meshwork, with a goal to lowering intraocular pressure and aiming to have the new trabecular meshwork function better than existing trabecular meshwork; use of supportive cells in the retina to protect against degeneration of retinal ganglion cells (RGCs); and differentiation of stem cells into RGCs so that damaged cells in the retina are replaced, with the hope that they would then re-establish axons and reconstitute the optic nerve. 

One of the most recent publications identified growth and differentiation factor-15, a ligand in the transforming growth factor-beta (TGF-beta), as an important promoter of RGC differentiation in the developing retina in rodent models and human embryonic stem cells. Curr Biol. 2019 Jun 17;29(12):1963-1975.e5.

Related: Researchers find long-term statin use linked to lower POAG risk 

Investigators have successfully transplanted RGCs that have survived, migrated and integrated into the retina in rodent models, but more investigations are needed before this research translates to clinical practice, according to Dr. Jones.

“Is it ready for prime time?” she asked. “There have not been those key trials to move this (candidate therapies) from the bench to the beside.” 

Dr. Jones noted that researchers are much less further along in glaucoma than researchers in retina]. 

“In glaucoma, we do not yet have well-designed clinical trials that are moving stem cell therapies to human testing.”

Related: Glaucoma genetics working toward a cure 

Conclusion

Dr. Jones noted that when it comes to glaucoma, there is not enough known to get these stem-cell therapies to work in vivo in humans.

“What we will need are clinical trials which are randomly selected with a placebo arm, and these are generally very expensive and very slow to start,” she said. “At this point, we are looking at two to three patients in phase I trials to get us going.”

Technologies to image the health of RGCs in vivo are needed, Dr. Jones concluded. 

“Candidate therapies that allow us to protect RGCs, rescue injured and dying RGCs, replace non-viable RGCs, and regenerate the optic nerve (are needed), as are randomized, clinical trials with control arms to allow us to test the efficacy of new therapies in humans,” she said. 

Read more glaucoma content 

Leslie Jones, MD
P: 202-865-1257
This article is based on Dr. Jones' presentation at the 51st Sally Letson Symposium in Ottawa, Ontario, Canada. Dr. Jones is chairwoman of Ophthalmology at Howard University in Washington, D.C. She is director of Glaucoma Services and the department's residency program. She has no financial disclosures related to her discussion.