A groundbreaking stem cell trial offers hope for millions with progressive conditions that end in sight loss, the Daily Mail has today reported. The high profile study was covered in different ways by news sources, with The Independent going as far to say patients had been ‘cured’ by a stem cell ‘miracle’.
The news is based on a small but important clinical trial that tested the safety of using human embryonic stem cells. The trial treated two people with progressive eye conditions affecting the macula, the part of the eye responsible for central vision. One patient had age-related macular degeneration, a common cause of visual loss in older adults. The other patient had Stargardt’s macular dystrophy, a rare hereditary disease that causes macular degeneration in adolescence. Both patients had end-stage disease with severe central vision loss.
In the study researchers developed stem cells into cell types found within the eye and carefully injected the cells into specific locations within the eye. After monitoring patients for four months the researchers found that neither patient had problems with abnormal cell growth, tumours, graft rejection or other safety issues. They also reported improvements in their vision, although not complete reversal of their conditions.
While certainly impressive, this small trial was designed to help establish the safety of the procedure, not whether it was effective. As such it helps support the safety of the treatment but it is far too early to declare the treatment as a ‘cure’ for blindness.
Where did the story come from?
The study was carried out by researchers from The University of California and the biotechnology company, Advanced Cell Technology in the US. The study was published in the peer-reviewed medical journal The Lancet.
BBC News reported this research well, highlighting that it was a small, preliminary safety study and that further follow-up is needed. The Independent’s headline was misleading, as this study did not demonstrate that a patient’s blindness was cured. However, within the main body of its article the newspaper made it clear that the study was a small trial to assess safety rather than effectiveness. The Daily Mail also said that it was a safety trial and their reporting was appropriate.
What kind of research was this?
This clinical study looked at the safety of transplanting human embryonic stem cells into two people with different types of eye disease: one person with Stargardt’s macular dystrophy and one person with dry age-related macular degeneration.
Age-related macular degeneration (AMD) is an eye condition that affects the macula, which is the central part of the retina found across the back of the eyeball. The macula is responsible for central vision. The condition is most often seen in people over the age of 65, and is the most common cause of visual loss in the developed world.
AMD is usually described as being dry or wet. Dry AMD, as the person in this study had, is the most common and less severe form and means that there is gradual degeneration of the retinal cells. It may or may not lead to complete visual loss. If there is progression to the more severe form, wet AMD, the condition also involves abnormal blood vessels growing within the retina (in an attempt to try and supply blood to the damaged macula). These abnormal vessels are fragile and can swell and bleed into the eye causing considerable damage to the macula and loss of vision over a comparatively short space of time. This study did not include people with wet AMD.
Stargardt’s macular dystrophy is a rare, inherited form of macular degeneration. Progressive vision loss usually starts before the age of 20 years, and as there is currently no available treatment. The condition usually leads to complete loss of central vision at a young age.
Stem cells have the ability to develop into various cell types. In this study the researchers used a type of stem cell derived from human embryonic tissue, which had then been developed into retinal cells. The researchers said that there were potential side effects of using these cells, included the cells dividing in an uncontrolled manner, forming tissue in the wrong position, and causing an immune rejection.
As is normal when developing new treatments, the researchers were carrying out a safety study to make sure the treatment was safe for humans. For their trial they used only one person with Stargardt’s disease and one person with dry AMD. As there were only two people in this study, with no control or comparison group, it is not possible to say how effective this treatment is at this stage. Larger follow-up trials would be needed to determine how effective treatment with this technology actually is.
What did the research involve?
The researchers recruited two people experiencing the end stage of their disease, which had left them with central vision loss but no other eye problems. They also had a cancer-free medical history and were able to undergo the immunosuppression needed for the treatment. They were also judged as psychologically suitable to participate in the first trial of this type involving eye stem cell treatment.
The researchers made human embryonic stem cells develop into retinal cells, using mouse skin cells to grow them on. The researchers then purified the cells so that there were no mouse cells remaining and then selected patches of retinal cells. They had already determined the best way to handle and store these cells in previous experimental work.
The two participants received immunosuppressive treatment the week before their transplant and for an additional 12 weeks. The researchers prepared a 1ml solution containing a known number of the retinal cells. They chose a specific area of the retina on which to inject these cells. Each patient had cells injected into one eye only, which is a common practice for trials of new treatments that could potentially damage the eyes.
What were the basic results?
The researchers were able to make retinal cells that were over 99% pure. As the cells had previously been exposed to animal cells, they tested the cells extensively for any contamination, including animal and human viruses.
They did not see any excessive or abnormal growth of the transplanted cells in either patient or any tumour formation. The transplanted cells were growing in the correct place, except one cell in the patient with Stargardt’s macular dystrophy. However, this cell was not dividing. There was no clinically detectable inflammation in the eyes of either patient and no signs of cataract, glaucoma, retinal detachment or increased pressure in the eye. Neither patient experienced pain or sensitivity to light.
The researchers could see that the cell transplant had survived in the patient with Stargardt’s macular dystrophy, and the amount of pigment in these cells increased from one week after the transplant up until the third month. Pigment is crucial for vision as it allows light entering the eye to be absorbed and converted into signals relayed to the brain.
Both patients showed functional improvement in their sight following treatment, despite not seeing anatomical evidence that the cells had survived in the patient with AMD. The patient with Stargardt’s macular degeneration could only determine hand motions before the treatment but after two weeks could count fingers using their treated eye. Her vision continued to improve over the next three months.
How did the researchers interpret the results?
The researchers say that the therapeutic use of human embryonic stem cells poses daunting challenges but that their results provide clinical evidence suggesting that human embryonic stem cells might safely be transplanted into human patients.
They say that so far, "the cells seem to have transplanted into both patients without abnormal proliferation, tumour formation, graft rejection or any untoward pathological reactions or safety signals". However, they add that continued follow-up and further study is needed.
This study tested the safety of these cells in people who had end-stage dry AMD and Stargardt’s macular degeneration. The researchers said that the ultimate therapeutic goal is to treat people earlier in the hope of increasing the likelihood of being able to safeguard their vision.
This was a small clinical trial that assessed the safety of using stem cell technology to treat one person with Stargardt’s macular dystrophy and one person with dry age-related macular degeneration. Specifically, it looked at the use of retinal cells that had been made from human embryonic stem cells.
The primary focus of this research was to see whether this procedure would be safe, not whether it was effective. The researchers found that neither of the patients had problems with abnormal cell growth, tumour formation, graft rejection or any other pathological reaction or safety issues, all of which are potential problems in this type of treatment.
The researchers followed the patients over four months but say that further follow-up is needed to observe the long-term effects of this treatment.
Although measuring the effectiveness of the treatment – whether it improved vision – was not the main aim of this study, both patients showed some improvement in vision. However, it should not be assumed that the treatment is effective, as it is not possible to say whether these improvements would be sustained in the long term. As only two people were treated, the response of a variety of people with central vision loss would have to be assessed in a larger trial.
This careful research has demonstrated that this type of transplant could be safe in the short term, and paves the way for larger trials under carefully controlled conditions. However, it is far too early to say whether this treatment could be a cure for blindness, as The Independent suggested.