Science & Research
A NEW WAY TO TREAT BLINDNESS USING MODIFIED STEM CELLS
In the middle of the eye’s retina is a millimetre-sized area called the macula, where cones are densely packed. Cones are the photoreceptors that detect colours and enable us to see sharply. In dry macular degeneration the support cells that cones need – the retinal pigment epithelium (RPE) – die, creating areas without cones. Anders Kvanta, professor of ophthalmology and senior physician at St. Erik Eye Hospital, Karolinska University Hospital in Solna, describes how the surface of dead cells appears to darken when using an imaging technique called fundus autofluorescence.
“The area without cells turns black and the eroded areas resemble a map in contrast to areas with healthy cells that remain light,” he says.
In Sweden 1,500 people are diagnosed with dry macular degeneration every year and more than 100,000 people live with the disease, which gradually but relentlessly destroys their vision.
For more than 10 years Anders Kvanta has collaborated with stem cell researcher Fredrik Lanner, a senior researcher at the Department of Clinical Science, Intervention and Technology at Karolinska Institutet in Huddinge.
“I was previously most interested in understanding how embryonic stem cells develop, but our collaboration has shown me how we can use stem cells to actually treat people and possibly cure a serious eye disease,” he says.
In the project A first-in-human clinical trial on embryonic stem cell-derived retinal cells for macular degeneration patients will be treated using a completely new method, which involves providing them with new and healthy cells in their damaged eye.
The researchers explain that it has long been said that there is no treatment for dry macular degeneration, something that today is partly true. This is because in the USA there is an approved drug that slows the progression of the disease, as demonstrated by slower growth of the area with dead cells in the eye.
“But there is no connection to improving visual function. Nor is the drug approved in Europe,” says Anders Kvanta, continuing:
“Our dream is not only to slow the rate of deterioration, but in the future to also be able to recover lost sight.”
The upcoming clinical trial will primarily test the safety of the new method, however
“Of course we hope it will be effective, but we cannot count on it at this stage,” he says.
Going from cultivating a specific type of cell from stem cells to being able to use these clinically is a lengthy process. In an important study along the way, the researchers tried injecting a suspension of the developed retinal pigment cells under the retina of rabbits, whose eyes are similar in size to ours.
“The cells formed a fine layer exactly as we want them to, without any clumps,” says Anders Kvanta.
The study was published in Stem Cell Reports in 2016. Another important step towards a clinical trial was developing a protocol for producing retinal pigment cells from stem cells in a scalable manner, which they published in Nature Communications in 2020.
Fredrik Lanner points out that they are replacing precisely the cells that have been damaged.
“Unlike some irresponsible studies which simply inject stem cells and hope for the best, we know exactly what kind of cells we are working with and what quantities we are using,” he says.
The new clinical trial will commence in 2025 and will involve 15 patients with severe dry macular degeneration. Both eyes should be affected, and the one worst affected will be treated. Anders Kvanta will then perform vitreoretinal surgery, which involves removing the vitreous body so that the surgeon can access the retina. The new cells are then injected under the retina using a fine needle.
“We create a small, controlled retinal detachment by forming a small blister. Nature then flattens the blister elegantly within a day, and hopefully we have then created the layer of cells that we saw in the rabbits,” he says.
To prevent rejection of the cells by the immune system, the patient will receive cortisone in tablet form. In addition, an implant the size of a grain of rice will be placed in the eye to release cortisone locally for three months.
The results will be measured using imaging techniques to study the extent of the area with dead cells, but also to study how the new cells are integrated into the eye. This can be observed using a type of layer-by-layer X-ray called optical coherence tomography, in which many two-dimensional images are combined to form a three-dimensional image.
“After all, we also want to measure how the retina above the transplanted cells is doing,” says Anders Kvanta.
This is done using a completely new technology, adaptive optics, where individual cells can be seen as small rings. The researchers will also continuously gather information on how the patients experience the situation and whether they possibly notice any change in their vision. They have chosen not to carry out ‘placebo surgeries’ where the surgery is performed without adding any cells; instead, all patients in the study will receive actual treatment.
“Our dream is not only to slow the rate of deterioration, but in the future to also be able to recover lost sight.”
“It’s not ethically justifiable to operate on people’s eyes if there is no chance of improvement,” says Anders Kvanta.
Fredrik Lanner points out that the same applies to other cell therapies, such as trials where patients with Parkinson’s disease are treated with cell transplants in the brain.
“There has been a paradigm shift and the authorities now consider that this type of trial both can and should be carried out without a true control group,” he says.
In their case, the patient’s untreated eye can also serve as a kind of internal control.
So what does the financial support from the Erling-Persson Foundation mean? On this, Fredrik Lanner is very clear:
“It’s absolutely crucial for being able to conduct the trial.”
He describes how they previously collaborated with Danish pharmaceutical company Novo Nordisk, which supported them in their work to develop protocols for manufacturing retinal pigment epithelial cells from embryonic stem cells. But just over a year ago the company made the strategic decision to stop working on ophthalmic drugs entirely.
“So there we were with our cultivated cells and couldn’t get any further,” says Fredrik Lanner.
Anders Kvanta adds:
“With the support from the Foundation we can now carry out the first clinical trial on humans, and test our method in practice. We have high hopes for getting good results, but it will take a few years,” he says.
