For 20 years, we’ve been waiting for human embryonic stem cells to deliver on their promise to provide new body parts, and deliver new treatments for diabetes, spinal cord injury, Parkinson’s or heart disease.
But when it comes to this tortoise race to the clinic, it seems the eyes have it.
Recently, a London-based group reported that two patients suffering from the “wet form” of age-related macular degeneration (AMD), had their eyesight improved by a graft of retinal pigmented epithelial cells (RPE) made from human embryonic stem cells.
Now, a group led by Mark Humayun at the University of Southern California (USC), US, reports success with the most common form of the disease – so-called “dry” AMD which accounts for 90% of cases. Of four patients injected with the cells, none experienced further vision loss, two had gains in visual function and one gained the ability to read more letters on an eye chart.
While research teams have previously grafted RPE cells into the eye as a soup, the new studies, both early Phase 1 trials, have used an intricate surgical technique to deliver the cells on a supportive membrane. Both recent studies also reported greater than expected success, which they attribute to the use of a membrane that replicates the natural single cell layered anatomy of the RPE.
“It’s a great result,” says Alice Pebay at the University of Melbourne in Australia, a stem cell researcher who focuses on eye disease. “What’s exciting is that they placed the cell on a structure, which is important for their long-term viability.”
AMD is one of the most common forms of age-related vision loss. In the US, it affects 14% of white Americans aged 80 and older. For blacks and Hispanics, the figure is 2%. With the ageing population, the incidence is projected to rise sharply.
The disease causes the most sensitive part of the retina, the tiny five-millimetre diameter patch known as the macula, to degenerate causing a loss of central vision.
The loss of the macula follows the loss of its support cells – the RPE layer directly below it. These both feed the macula and remove waste products, so researchers have long suspected that if they could replace them, they might save the macula.
What aided this idea is that RPE cells tend to form spontaneously within cultures of human embryonic stem cells (hES), and only a tiny number would be needed for each patient.
In the wet form of the disease, blood vessels grow across the retina, leak, and damage the underlying RPE. In the dry form, the RPE disintegrates without the help of blood vessels; fatty particles called drusen appear to be responsible.
Either way, replacing RPE cells might save the macula.
The London group, led by Pete Coffey at University College London, chose to target wet AMD.
While it is the less common form of the disease, it is also less severe because patients still retain a functional macula – which might, thus, be saved.
“The reason we went for wet is that we wanted to answer the question everyone wants to know: will they stop the disease,” says Coffey.
In their phase 1 safety trial, two patients, one a woman in her 60s, the other a man in his 80s, were treated with a patch of RPE cells in a single eye. By the end of a year, both experienced significant improvement in the treated eye.
The woman got back six lines of vision on an eye chart, enabling her to read between 60 and 80 words per minute. The man achieved five lines and is reading at 50 words per minute.
“It was a stunning result that absolutely exceeded expectation,” says Coffey. To prevent rejection of the cells, the patients had a capsule of steroids implanted in the back of the eye.
In the current USC study, RPE cells were also delivered on a synthetic membrane, and the patients were injected with a drug to prevent the rejection of the graft.
As a Phase 1/2a trial, it was primarily meant to assess the safety of the implant, so the researchers were delighted to discover that it not only integrated into the patients’ retinas, it also appeared to improve vision.
This was a surprise, because the patients had advanced disease and had lost much of their retinal tissue, says Amir Kashani, the lead author and the surgeon who performed the tricky procedure.
“We’re certainly happy see it but it wasn’t an expectation,” he says. “The next step is to try the procedure in less advanced cases.”
Overall, the growing number of studies using RPE cells for AMD is encouraging researchers to hope that in the next five years or so it will become available as a widespread treatment.