The first published results of trials using cells derived from human embryonic stem cells appear to show they have passed an initial safety hurdle. In The Lancet this week, researchers report that two nearly blind patients, one with Stargardt’s macular dystrophy and the other with dry age-related macular degeneration (the leading cause of blindness in developed countries), showed measurable improvements in vision that lasted for more than four months after receiving injections of retinal pigment epithelium cells derived from human embryonic stem cells.

The retinal pigment epithelium (RPE) cells were developed by the US stem cell company Advanced Cell Technology (ACT), and the trials were conducted at the Jules Stein Eye Institute at the University of California, Los Angeles. The report appeared online in The Lancet on Monday 23 January.

Both trials are designed as prospective “open label” trials to test the safety and tolerability of sub-retinal transplantation of RPE cells made from stem cells derived from human embryos.

As well as these two trials taking place in the US, another trial for SMD is just starting in the UK, and the first patient was treated at Moorfields Eye Hospital in London last Friday.

The researchers write in The Lancet:

“It has been 13 years since the discovery of human embryonic stem cells (hESCs). Our report provides the first description of hESC-derived cells transplanted into human patients.”

The apparent success of the trials, which at best showed that vision improved slightly, and at worst, that it did not deteriorate and there were no adverse safety issues, could signify a major boost to the field of stem cell research which has found itself in the doldrums lately.

And in this particular case, they offer hope to millions of people with AMD, whose numbers are increasing every year. In the US alone, the number of people with AMD is estimated to reach 2.95 million by 2020, according to the Centers for Disease Control and Prevention (CDC).

Macular degeneration, often called age-related macular degeneration (AMD), is an eye disorder associated with aging where people’s vision becomes less sharp and they gradually lose central vision, which is essential every day tasks such as reading and driving.

AMD affects the macula, the middle part the retina that allows the eye to see fine details. There are two forms of AMD, wet and dry. And although dry is by far the most common form of AMD, unfortunately drugs are only available for wet AMD.

Dr Robert Lanza is the chief scientific officer of ACT and the senior author of the paper. He told the press the “safety and engraftment data to date look very encouraging”, and that despite the progressive nature of Stargardt’s macular dystrophy (SMD) and AMD:

“… the vision of both patients appears to have improved after transplantation of the cells, even at the lowest dosage.”

He pointed out this was particularly important, because they want eventually to be able to treat patients earlier in the course of the disease, before too much damage is done and more significant results might be expected.

There are two main aspects to the trials: one is the safety aspect, and the other is how much did the treatment improve the vision of the patients.

On the safety side, the main concerns around using cells derived from stem cells are to ensure they do not continue to grow in a disorganized fashion and behave like cancer cells in tumors (“hyperproliferation” and “tumorigenicity”), that the new tissue grows in the right place (with no “ectopic tissue formation”), and that the patient’s immune system does not reject it.

The researchers find that at four months following treatment, there is no evidence of this:

“We did not identify signs of hyperproliferation, abnormal growth, or immune mediated transplant rejection in either patient during the first 4 months.”

On the vision improvement side, the results are less conclusive, because there is no consensus about how to measure vision improvement.

The authors acknowledge this in their report:

“Although there is little agreement between investigators on visual endpoints in patients with low vision, it is encouraging that during the observation period neither patient lost vision.”

They describe the improvements they measured as follows:

“Best corrected visual acuity improved from hand motions to 20/800 (and improved from 0 to 5 letters on the Early Treatment Diabetic Retinopathy Study [ETDRS] visual acuity chart) in the study eye of the patient with Stargardt’s macular dystrophy, and vision also seemed to improve in the patient with dry age-related macular degeneration (from 21 ETDRS letters to 28).”

They suggest their results mean that since the RPE cells derived from human embryo stem cells “showed no signs of hyperproliferation, tumorigenicity, ectopic tissue formation, or apparent rejection after 4 months”, then “the future therapeutic goal will be to treat patients earlier in the disease processes, potentially increasing the likelihood of photoreceptor and central visual rescue”.

The principal investigator of the study and senior author of the report is Dr Steven Schwartz, Ahmanson Professor of Ophthalmology at the David Geffen School of Medicine at UCLA and retina division chief at the University’s Jules Stein Eye Institute. He said:

“It is an honor to initiate the translational research process as we begin to take stem cell biology out of the laboratory and into the operating room.”

He said the positive early results of these preliminary safety trials and the hint there could be benefits to patients in terms vision improvement, “makes this is an exciting time for ophthalmology and regenerative medicine”.

Both trials are due to report results at 12 months, the primary end-point. Each trial will enrol 12 patients: that is 12 with SMD and 12 with dry AMD. There will be three doses of RPE. Both the SMD and dry AMD patients in the current report received the smallest dose (50,000 cells) of fully-differentiated RPE cells derived from hESCs.

Lanza thanked the volunteer patients, both in the US and the UK:

“We would like to thank the patients for their willingness to participate in these safety studies. It has provided the scientific community with important data and experience that will help advance efforts in the regenerative medicine field.”

For further information about AMD see this fact sheet from the National Eye Institute in the US.

Written by Catharine Paddock PhD